Showing papers in "The Journal of Nuclear Medicine in 2006"

The Detection of Bone Metastases in Patients with High-Risk Prostate Cancer: 99mTc-MDP Planar Bone Scintigraphy, Single- and Multi-Field-of-View SPECT, 18F-Fluoride PET, and 18F-Fluoride PET/CT

Abstract: The aim of this study was to compare the detection of bone metastases by 99mTc-methylene diphosphonate (99mTc-MDP) planar bone scintigraphy (BS), SPECT, 18F-Fluoride PET, and 18F-Fluoride PET/CT in patients with high-risk prostate cancer. Methods: In a prospective study, BS and 18F-Fluoride PET/CT were performed on the same day in 44 patients with high-risk prostate cancer. In 20 of the latter patients planar BS was followed by single field-of-view (FOV) SPECT and in 24 patients by multi-FOV SPECT of the axial skeleton. Lesions were interpreted separately on each of the 4 modalities as normal, benign, equivocal, or malignant. Results: In patient–based analysis, 23 patients had skeletal metastatic spread (52%) and 21 did not. Categorizing equivocal and malignant interpretation as suggestive for malignancy, the sensitivity, specificity, positive predictive value, and negative predictive value of planar BS were 70%, 57%, 64%, and 55%, respectively, of multi-FOV SPECT were 92%, 82%, 86%, and 90%, of 18F-Fluoride PET were 100%, 62%, 74%, and 100%, and of 18F-Fluoride PET/CT were 100% for all parameters. Using the McNemar test, 18F-Fluoride PET/CT was statistically more sensitive and more specific than planar or SPECT BS (P

Consensus Recommendations for the Use of 18F-FDG PET as an Indicator of Therapeutic Response in Patients in National Cancer Institute Trials

Abstract: Many therapeutic clinical trials have proposed using a measure of metabolic change to assess therapeutic response rather than relying on conventional anatomic measurements of changes in tumor size on CT or MRI. PET assessment of changes in 18F-FDG uptake by tumors is gaining acceptance as such a

Procedure Guideline for Tumor Imaging with 18F-FDG PET/CT 1.0

Abstract: The purpose of these guidelines is to assist physicians in recommending, performing, interpreting, and reporting the results of 18F-FDG PET/CT for oncologic imaging of adult and pediatric patients. PET is a tomographic scintigraphic technique in which a computer-generated image of local radioactive

Impact of Animal Handling on the Results of 18F-FDG PET Studies in Mice

Abstract: Small-animal PET scanning with 18F-FDG is increasingly used in murine models of human diseases. However, the impact of dietary conditions, mode of anesthesia, and ambient temperature on the biodistribution of 18F-FDG in mice has not been systematically studied so far. The aim of this study was to determine how these factors affect assessment of tumor glucose use by 18F-FDG PET and to develop an imaging protocol that optimizes visualization of tumor xenografts. Methods: Groups of severe combined immunodeficient (SCID) mice were first imaged by microPET with free access to food, at room temperature (20°C), and no anesthesia during the uptake period (reference condition). Subsequently, the impact of (a) fasting for 8–12 h, (b) warming the animals with a heating pad (30°C), and (c) general anesthesia using isoflurane or ketamine/xylazine on the 18F-FDG biodistribution was evaluated. Subcutaneously implanted human A431 epidermoid carcinoma and U251 glioblastoma cells served as tumor models. Results: Depending on the study conditions, 18F-FDG uptake by normal tissues varied 3-fold for skeletal muscle, 13-fold for brown adipose tissue, and 15-fold for myocardium. Warming and fasting significantly reduced the intense 18F-FDG uptake by brown adipose tissue observed under the reference condition and markedly improved visualization of tumor xenografts. Although tumor 18F-FDG uptake was not above background activity under the reference condition, tumors demonstrated marked focal 18F-FDG uptake in warmed and fasted animals. Quantitatively, tumor 18F-FDG uptake increased 4-fold and tumor-to-organ ratios were increased up to 17-fold. Ketamine/xylazine anesthesia caused marked hyperglycemia and was not further evaluated. Isoflurane anesthesia only mildly increased blood glucose levels and had no significant effect on tumor 18F-FDG uptake. Isoflurane markedly reduced 18F-FDG uptake by brown adipose tissue and skeletal muscle but increased the activity concentration in liver, myocardium, and kidney. Conclusion: Animal handling has a dramatic effect on 18F-FDG biodistribution and significantly influences the results of microPET studies in tumor-bearing mice. To improve tumor visualization mice should be fasted and warmed before 18F-FDG injection and during the uptake period. Isoflurane appears well suited for anesthesia of tumor-bearing mice, whereas ketamine/xylazine should be used with caution, as it may induce marked hyperglycemia.

Performance Test of an LSO-APD Detector in a 7-T MRI Scanner for Simultaneous PET/MRI

Abstract: PET combined with CT has proven to be a valuable multimodality imaging device revealing both functional and anatomic information. Although PET/CT has become completely integrated into routine clinical application and also has been used in small-animal imaging, CT provides only limited soft-tissue contrast and, in preclinical studies, exposes the animal to a relatively high radiation dose. Unlike CT, MRI provides good soft-tissue contrast even without application of contrast agents and, furthermore, does not require ionizing radiation. Methods: This project focused on combining a high-resolution PET scanner with a 7-T MRI system for animal research. Because classic PET detectors based on photomultiplier tubes cannot be used in high magnetic fields, we used a detector technology based on 10 × 10 lutetium oxyorthosilicate crystal arrays and 3 × 3 avalanche photodiode arrays. A ring of such PET detectors will ultimately be used as an insert for the 119-mm-diameter MRI bore. Results: Initial measurements with 1 PET detector module in the 7-T field during application of MRI sequences were encouraging. Position profiles from the PET detectors and a first MR image of a mouse could be acquired simultaneously. Conclusion: Further work will concentrate on the construction of a full PET detector ring with compact, integrated electronics.

18F-FDOPA PET Imaging of Brain Tumors: Comparison Study with 18F-FDG PET and Evaluation of Diagnostic Accuracy

Abstract: We evaluated the amino acid and glucose metabolism of brain tumors by using PET with 3,4-dihydroxy-6-18F-fluoro-l-phenylalanine (18F-FDOPA) and 18F-FDG. Methods: Eighty-one patients undergoing evaluation for brain tumors were studied. Initially, 30 patients underwent PET with 18F-FDOPA and 18F-FDG within the same week. Tracer kinetics in normal brain and tumor tissues were estimated. PET uptake was quantified by use of standardized uptake values and the ratio of tumor uptake to normal hemispheric tissue uptake (T/N). In addition, PET uptake with 18F-FDOPA was quantified by use of ratios of tumor uptake to striatum uptake (T/S) and of tumor uptake to white matter uptake. The accuracies of 18F-FDOPA and 18F-FDG PET were determined by comparing imaging data with histologic findings and findings of clinical follow-up of up to 31 mo (mean, 20 mo). To further validate the accuracy of 18F-FDOPA PET, 18F-FDOPA PET was performed with an additional 51 patients undergoing brain tumor evaluation. Results: Tracer uptake in tumors on 18F-FDOPA scans was rapid, peaking at approximately 15 min after intravenous injection. Tumor uptake could be distinguished from that of the striatum by the difference in peak times. Both high-grade and low-grade tumors were well visualized with 18F-FDOPA. The sensitivity for identifying tumors was substantially higher with 18F-FDOPA PET than with 18F-FDG PET at comparable specificities, as determined by simple visual inspection, especially for the assessment of low-grade tumors. Using receiver-operating-characteristic curve analysis, we found the optimal threshold for 18F-FDOPA to be a T/S of greater than 1.0 (sensitivity, 96%; specificity, 100%) or a T/N of greater than 1.3 (sensitivity, 96%; specificity, 86%). The high diagnostic accuracy of 18F-FDOPA PET at these thresholds was confirmed with the additional 51 patients (a total of 81 patients: sensitivity, 98%; specificity, 86%; positive predictive value, 95%; negative predictive value, 95%). No significant difference in tumor uptake on 18F-FDOPA scans was seen between low-grade and high-grade tumors (P = 0.40) or between contrast-enhancing and nonenhancing tumors (P = 0.97). Radiation necrosis was generally distinguishable from tumors on 18F-FDOPA scans (P

Simultaneous Acquisition of Multislice PET and MR Images: Initial Results with a MR-Compatible PET Scanner

Abstract: PET and MRI are powerful imaging techniques that are largely complementary in the information they provide. We have designed and built a MR-compatible PET scanner based on avalanche photodiode technology that allows simultaneous acquisition of PET and MR images in small animals. Methods: ThePETscannerinsertusesmagneticfield‐insensitive,positionsensitive avalanche photodiode (PSAPD) detectors coupled, via short lengths of optical fibers, to arrays of lutetium oxyorthosilicate (LSO) scintillator crystals. The optical fibers are used to minimize electromagnetic interference between the radiofrequency and gradient coils and the PET detector system. The PET detector module components and the complete PET insert assembly are described. PET data were acquired with and without MR sequences running, and detector flood histograms were compared with the ones generated from the data acquired outside the magnet. A uniform MR phantom was also imaged to assess the effect of the PET detector on the MR data acquisition. Simultaneous PET and MRI studies of a mouse were performed ex vivo. Results: PSAPDs can be successfully used to read out large numbers of scintillator crystals coupled through optical fibers with acceptable performance in terms of energy and timing resolution and crystal identification. The PSAPD-LSO detector performs well in the 7-T magnet, and no visible artifacts are

Tumor Targeting by an Aptamer

Abstract: Aptamers are small oligonucleotides that are selected to bind tightly and specifically to a target molecule. We sought to determine whether aptamers have potential for in vivo delivery of radioisotopes or cytotoxic agents. Methods: TTA1, an aptamer to the extracellular matrix protein tenascin-C, was prepared in fluorescent and radiolabeled forms. After in vivo administration, uptake and tumor distribution of Rhodamine Red-X–labeled aptamer was studied by fluorescence microscopy. In glioblastoma (U251) and breast cancer (MDA-MB-435) tumor xenografts, biodistribution and imaging studies were performed using TTA1 radiolabeled with 99mTc. Tenascin-C levels and tumor uptake were studied in a variety of additional human tumor xenografts. To assess the effect of radiometal chelate on biodistribution, mercapto-acetyl diglycine (MAG2) was compared with diethylenetriaminepentaacetic acid and with MAG2–3,400-molecular-weight PEG (PEG3,400). Results: Intravenous injection of fluorescent aptamer TTA1 produced bright perivascular fluorescence in a xenografted human tumor within 10 min. In the ensuing 3 h, fluorescence diffused throughout the tumor. Labeled with 99mTc, TTA1 displayed rapid blood clearance, a half-life of less than 2 min, and rapid tumor penetration: 6% injected dose (%ID)/g at 10 min. Tumor retention was durable, with 2.7 %ID/g at 60 min and a long-lived phase that stabilized at 1 %ID/g. Rapid tumor uptake and blood clearance yielded a tumor-to-blood ratio of 50 within 3 h. Both renal and hepatic clearance pathways were observed. Using the 99mTc-labeled aptamer, images of glioblastoma and breast tumors were obtained by planar scintigraphy. Aptamer uptake, seen in several different human tumors, required the presence of the target protein, human tenascin-C. Modification of the MAG2 radiometal chelator dramatically altered the uptake and clearance patterns. Conclusion: TTA1 is taken up by a variety of solid tumors including breast, glioblastoma, lung, and colon. Rapid uptake by tumors and rapid clearance from the blood and other nontarget tissues enables clear tumor imaging. As synthetic molecules, aptamers are readily modified in a site-specific manner. A variety of aptamer conjugates accumulate in tumors, suggesting imaging and potentially therapeutic applications.

Iodine Biokinetics and Dosimetry in Radioiodine Therapy of Thyroid Cancer: Procedures and Results of a Prospective International Controlled Study of Ablation After rhTSH or Hormone Withdrawal

Abstract: study of the effectiveness of ablation therapy with 3.7 GBq 131 I in differentiated thyroid cancer after stimulation with recombinant human TSH (rhTSH) or by thyroid hormone withdrawal (THW) are presented. Methods: Sixty-three patients were randomized after thyroidectomy to either the THW or the rhTSH group. Scintigraphic neck images were acquired starting 48 h after radioiodine administration to assess biokinetics in the thyroid remnant. The activity in blood samples was quantified and data from whole-body probe measurements and scintigraphic whole-body scans were combined to deduce retention curves in blood and whole body, respectively. The absorbed dose to the blood was calculated using a modified approach based on the formalism of the MIRD Committee of the Society of Nuclear Medicine. Results: The effective half-time in the remnant thyroid tissuewassignificantlylongerafterrhTSHthanTHW(67.6 648.8 vs. 48.0 6 52.6 h, respectively; P 5 0.01), whereas the observed differencesofthemean48-h 131 Iuptakes(0.5% 60.7%vs.0.9% 6 1.0% after THW; P 5 0.1) and residence times (0.9 6 1.3 vs. 1.4 6 1.5 h after THW; P 5 0.1) between the rhTSH and THW groups were not statistically significant. The specific absorbed dose to the blood was significantly (P ,0.0001) lower after administration of rhTSH (mean, 0.109 6 0.028 mGy/MBq; maximum, 0.18 mGy/MBq) than after THW (mean, 0.167 6 0.061 mGy/MBq; maximum, 0.35 mGy/MBq), indicating that higher activities of radioiodine might be safely administered after exogenousstimulation withrhTSH.Conclusion:Indication ofaninfluence of the residence time of radioiodine in the blood on the fractional uptake into thyroid remnant was found. A novel regimen is proposed in which therapeutic activities to be administered are determined from the individual specific blood dose.

Quantitative Analysis in Nuclear Medicine Imaging

Abstract: Quantitative Analysis in Nuclear Medicine Imaging is an in-depth review of single-photon and PET nuclear medicine image reconstruction, correction, modeling, and analysis techniques, with a particular emphasis on quantitative imaging for both diagnostic and therapeutic (i.e., internal radionuclide

Quantitative PET Imaging of Tumor Integrin αvβ3 Expression with 18F-FRGD2

Abstract: The development of noninvasive methods to visualize and quantify integrin αvβ3 expression in vivo appears to be crucial for the success of antiangiogenic therapy based on integrin antagonism. Precise documentation of integrin receptor levels will allow appropriate selection of patients who will most likely benefit from an antiintegrin treatment regimen. Imaging can also be used to provide an optimal dosage and time course for treatment based on receptor occupancy studies. In addition, imaging integrin expression will be important to evaluate antiintegrin treatment efficacy and to develop new therapeutic drugs with favorable tumor targeting and in vivo kinetics. We labeled the dimeric RGD peptide E[c(RGDyK)]2 with 18F and evaluated its tumor-targeting efficacy and pharmacokinetics of 18F-FB–E[c(RGDyK)]2 (18F-FRGD2). Methods: E[c(RGDyK)]2 was labeled with 18F by conjugation coupling with N-succinimidyl-4-18F-fluorobenzoate (18F-SFB) under a slightly basic condition. The in vivo metabolic stability of 18F-FRGD2 was determined. The diagnostic value after injection of 18F-FRGD2 was evaluated in various xenograft models by dynamic microPET followed by ex vivo quantification of tumor integrin level. Results: Starting with 18F− Kryptofix 2.2.2./K2CO3 solution, the total reaction time for 18F-FRGD2, including final high-performance liquid chromatography purification, is about 200 ± 20 min. Typical decay-corrected radiochemical yield is 23% ± 2% (n = 20). 18F-FRGD2 is metabolically stable. The binding potential extrapolated from graphical analysis of PET data and Logan plot correlates well with the receptor density measured by sodium dodecyl sulfate polyacrylamide electrophoresis and autoradiography in various xenograft models. The tumor-to-background ratio at 1 h after injection of 18F-FRGD2 also gives a good linear relationship with the tumor tissue integrin level. Conclusion: The dimeric RGD peptide tracer 18F-FRGD2, with high integrin specificity and favorable excretion profile, may be translated into the clinic for imaging integrin αvβ3 expression. The binding potential calculated from simplified tracer kinetic modeling such as the Logan plot appears to be an excellent indicator of tumor integrin density.

Performance Evaluation of the GE Healthcare eXplore VISTA Dual-Ring Small-Animal PET Scanner

Abstract: We evaluated the performance characteristics of the eXplore VISTA dual-ring small-animal PET scanner, a stationary, ring-type, depth-of-interaction (DOI) correcting system designed to simultaneously maximize sensitivity, resolution, and resolution uniformity over a field of view sufficient to image rodent-sized animals. Methods: We measured the intrinsic spatial resolution response of the VISTA detector modules, spatial and volume resolution throughout a representative portion of the field of view, and imaged several common resolution phantoms to provide a qualitative picture of resolution performance. We obtained an axial sensitivity profile and measured central point source sensitivity, scatter fractions and noise equivalent count (NEC) rates for rat- and mouse-sized objects using different energy windows, and count rate linearity. In addition, we measured the energy and timing resolution of both of the crystal layers (cerium-doped gadolinium orthosilicate and cerium-doped lutetium–yttrium orthosilicate) that give VISTA machines a DOI compensation capability. We examined the effectiveness of this DOI compensation by comparing spatial resolution measurements with and without the DOI correction enabled. Finally, several animal studies were included to illustrate system performance in the field. Results: Spatial and volume resolutions averaged approximately 1.4 mm and 2.9 mm3, respectively (with 3-dimensional Fourier rebinning and 2-dimensional filtered backprojection image reconstructions and an energy window of 250–700 keV), along the central axis of the scanner, and the spatial resolution was better than 1.7 mm and 2.1 mm at 1 and 2 cm off the central axis, respectively. Central point source sensitivity measured approximately 4% with peak NEC rates of 126.8 kcps at 455 kBq/mL and 77.1 kcps at 141 kBq/mL for mouse- and rat-sized uniform, cylindric phantoms, respectively. The radial spatial resolution at 2.8 cm off axis with DOI compensation was 2.5 mm but degraded (by 56%) to 3.9 mm without DOI compensation (as would be the case with a geometrically identical scanner without DOI correction capability). Conclusion: These results indicate that the VISTA small-animal PET scanner is well suited to imaging rodent-sized animals. The combination of high spatial resolution, resolution uniformity, sensitivity, and count rate performance, made possible in part by the novel use of phoswich detector modules, confers significant technical advantages over machines with similar geometry but without DOI correction capability.

Brain White-Matter Volume Loss and Glucose Hypometabolism Precede the Clinical Symptoms of Huntington's Disease

Abstract: We studied the anatomic and functional changes in various brain areas during the course of Huntington9s disease (HD) in a large cohort of mutation-positive individuals (n = 71) encompassing the complete range of disability (presymptomatic through stage V), and in healthy controls, for the purpose of defining both degenerative and dysfunctional brain changes in the same subjects. Methods: We used an MRI and unsupervised multiparametric segmentation procedure based on a relaxometric approach to measure in vivo brain volumes in 71 subjects with presymptomatic to advanced HD. The same population was evaluated by 18F-FDG PET to assess variations in brain glucose metabolism. To predict age at onset in unaffected mutation carriers, we considered the estimated number of years from each subject9s age to manifested HD symptoms, for a given expanded triplet number. Results: Age-adjusted analyses confirmed that the 71 subjects as a group, as well as the subgroup of 24 unaffected presymptomatic subjects at risk for HD, had significantly smaller gray-matter and white-matter volumes and larger cerebrospinal fluid volumes than did controls (P

18F-FDG PET Definition of Gross Tumor Volume for Radiotherapy of Non–Small Cell Lung Cancer: Is a Single Standardized Uptake Value Threshold Approach Appropriate?

Abstract: PET with 18F-FDG has been used in radiation treatment planning for non–small cell lung cancer (NSCLC). Thresholds of 15%–50% the maximum standardized uptake value (SUVmax) have been used for gross tumor volume (GTV) delineation by PET (PETGTV), with 40% being the most commonly used value. Recent studies indicated that 15%–20% may be more appropriate. The purposes of this study were to determine which threshold generates the best volumetric match to GTV delineation by CT (CTGTV) for peripheral NSCLC and to determine whether that threshold can be generalized to tumors of various sizes. Methods: Data for patients who had peripheral NSCLC with well-defined borders on CT and SUVmax of greater than 2.5 were reviewed. PET/CT datasets were reviewed, and a volume of interest was determined to represent the GTV. The CTGTV was delineated by using standard lung windows and reviewed by a radiation oncologist. The PETGTV was delineated automatically by use of various percentages of the SUVmax. The PETGTV-to-CTGTV ratios were compared at various thresholds, and a ratio of 1 was considered the best match, or the optimal threshold. Results: Twenty peripheral NSCLCs with volumes easily defined on CT were evaluated. The SUVmax (mean ± SD) was 12 ± 8, and the mean CTGTV was 198 cm3 (97.5% confidence interval, 5–1,008). The SUVmax were 16 ± 5, 13 ± 9, and 3.0 ± 0.4 for tumors measuring greater than 5 cm, 3–5 cm, and less than 3 cm, respectively. The optimal thresholds (mean ± SD) for the best match were 15% ± 6% for tumors measuring greater than 5 cm, 24% ± 9% for tumors measuring 3–5 cm, 42% ± 2% for tumors measuring less than 3 cm, and 24% ± 13% for all tumors. The PETGTV at the 40% and 20% thresholds underestimated the CTGTV for 16 of 20 and 14 of 20 lesions, respectively. The mean difference in the volumes (PETGTV minus CTGTV [PETGTV – CTGTV]) at the 20% threshold was 79 cm3 (97.5% confidence interval, −922 to 178). The PETGTV at the 20% threshold overestimated the CTGTV for all 4 tumors measuring less than 3 cm and underestimated the CTGTV for all 6 tumors measuring greater than 5 cm. The CTGTV was inversely correlated with the PETGTV – CTGTV at the 20% threshold (R2 = 0.90, P

18F-FDG PET/CT in the Evaluation of Adrenal Masses

Abstract: Our purpose was to evaluate the performance of 18F-FDG PET/CT, using data from both the PET and the unenhanced CT portions of the study, in characterizing adrenal masses in oncology patients. Methods: One hundred seventy-five adrenal masses in 150 patients referred for 18F-FDG PET/CT were assessed. Final diagnosis was based on histology (n = 6), imaging follow-up (n = 118) of 6–29 mo (mean, 14 mo), or morphologic imaging criteria (n = 51). Each adrenal mass was characterized by its size; its attenuation on CT, expressed by Hounsfield units (HU); and the intensity of 18F-FDG uptake, expressed as standardized uptake value (SUV). Receiver operating characteristic curves were drawn to determine the optimal cutoff values of HU and SUV that would best discriminate between benign and malignant masses. Results: When malignant lesions were compared with adenomas, PET data alone using an SUV cutoff of 3.1 yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 98.5%, 92%, 89.3%, 98.9%, respectively. For combined PET/CT data, the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 98%, 97%, 100%, respectively. Specificity was significantly higher for PET/CT (P

PET of Vascular Endothelial Growth Factor Receptor Expression

Abstract: For solid tumors and metastatic lesions, tumor vascularity is a critical factor in assessing response to therapy. Here we report the first example, to our knowledge, of 64Cu-labeled vascular endothelial growth factor 121 (VEGF121) for PET of VEGF receptor (VEGFR) expression in vivo. Methods: VEGF121 was conjugated with 1,4,7,10-tetraazadodecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA) and then labeled with 64Cu for small-animal PET of mice bearing different sized U87MG human glioblastoma xenografts. Blocking experiments and ex vivo histopathology were performed to confirm the in vivo results. Results: There were 4.3 ± 0.2 DOTA molecules per VEGF121, and the VEGFR2 binding affinity of DOTA-VEGF121 was comparable to VEGF121. 64Cu labeling of DOTA-VEGF121 was achieved in 90 ± 10 min and the radiolabeling yield was 87.4% ± 3.2%. The specific activity of 64Cu-DOTA-VEGF121 was 3.2 ± 0.1 GBq/mg with a radiochemical purity of >98%. Small-animal PET revealed rapid, specific, and prominent uptake of 64Cu-DOTA-VEGF121 in small U87MG tumors (high VEGFR2 expression) but significantly lower and sporadic uptake in large U87MG tumors (low VEGFR2 expression). No appreciable renal clearance of 64Cu-DOTA-VEGF121 was observed, although the kidney uptake was relatively high likely due to VEGFR1 expression. Blocking experiments, immunofluorescence staining, and western blot confirmed the VEGFR specificity of 64Cu-DOTA-VEGF121. Conclusion: Successful demonstration of the ability of 64Cu-DOTA-VEGF121 to visualize VEGFR expression in vivo may allow for clinical translation of this radiopharmaceutical for imaging tumor angiogenesis and guiding antiangiogenic treatment, especially patient selection and treatment monitoring of VEGFR-targeted cancer therapy.

Imaging Prostate Cancer with 11C-Choline PET/CT

Abstract: The ability of 11C-choline and multimodality fusion imaging with integrated PET and contrast-enhanced CT (PET/CT) was investigated to delineate prostate carcinoma (PCa) within the prostate and to differentiate cancer tissue from normal prostate, benign prostate hyperplasia, and focal chronic prostatitis. Methods: All patients with PCa gave written informed consent. Twenty-six patients with clinical stage T1, T2, or T3 and biopsy-proven PCa underwent 11C-choline PET/CT after intravenous injection of 1,112 ± 131 MBq 11C-choline, radical retropubic prostatovesiculectomy, and standardized prostate tissue sampling. Maximal standardized uptake values (SUVs) of 11C-choline within 36 segments of the prostate were determined. PET/CT results were correlated with histopathologic results, prostate-specific antigen (PSA), Gleason score, and pT stage. Results: The SUV of 11C-choline in PCa tissue was 3.5 ± 1.3 (mean ± SD) and significantly higher than that in prostate tissue with benign histopathologic lesions (2.0 ± 0.6; P

Hypometabolism Exceeds Atrophy in Presymptomatic Early-Onset Familial Alzheimer's Disease

Abstract: The aim of the present study is to compare brain atrophy with hypometabolism as preclinical markers of Alzheimer9s disease (AD) by studying presymptomatic individuals from families with known early-onset autosomal dominant AD (FAD) carrying mutations in the Presenilin 1 gene. Methods: Seven asymptomatic at-risk FAD individuals (age, 35–49 y; 4 women; education ≥ 12 y) and 7 matched healthy control subjects received complete clinical, neuropsychologic, MRI, and 18F-FDG PET examinations. Regions of interest (ROIs: whole brain [WB], hippocampus [Hip], entorhinal cortex [EC], posterior cingulate cortex [PCC], inferior parietal lobule [IPL], and superior temporal gyrus (STG]) were drawn on the MRI scans of all subjects and used to measure volumes on MRI and glucose metabolism (MRglc) from the MRI-coregistered, atrophy-corrected PET scans. Results: Compared with controls and after correcting for head size, MRI volume reductions in FAD subjects were restricted to the IPL (18%, P

18F-FDG PET/CT for detecting nodal metastases in patients with oral cancer staged N0 by clinical examination and CT/MRI.

Abstract: 18F-FDG PET has a high accuracy in staging head and neck cancer, but its role in patients with clinically and radiographically negative necks (N0) is less clear. In particular, the value of combined PET/CT has not been determined in this group of patients. Methods: In a prospective study, 31 patients with oral cancer and no evidence of lymph node metastases by clinical examination or CT/MRI underwent 18F-FDG PET/CT before elective neck dissection. PET/CT findings were recorded by neck side (left or right) and lymph node level. PET/CT findings were compared with histopathology of dissected nodes, which was the standard of reference. Results: Elective neck dissections (26 unilateral, 5 bilateral; a total of 36 neck sides), involving 142 nodal levels, were performed. Only 13 of 765 dissected lymph nodes harbored metastases. Histopathology revealed nodal metastases in 9 of 36 neck sides and 9 of 142 nodal levels. PET was TP in 6 nodal levels (6 neck sides), false-negative in 3 levels (3 neck sides), true-negative in 127 levels (23 neck sides), and false-positive in 6 levels (4 neck sides). The 3 false-negative findings occurred in metastases smaller than 3 mm or because of inability to distinguish between primary tumor and adjacent metastasis. TP and false-positive nodes exhibited similar standardized uptakes (4.8 ± 1.1 vs. 4.2 ± 1.0; P = not significant). Sensitivity and specificity were 67% and 85% on the basis of neck sides and 67% and 95% on the basis of number of nodal levels, respectively. If a decision regarding the need for neck dissection had been based solely on PET/CT, 3 false-negative necks would have been undertreated, and 4 false-positive necks would have been overtreated. Conclusion:18F-FDG PET/CT can identify lymph node metastases in a segment of patients with oral cancer and N0 neck. A negative test can exclude metastatic deposits with high specificity. Despite reasonably high overall accuracy, however, the clinical application of PET/CT in the N0 neck may be limited by the combination of limited sensitivity for small metastatic deposits and a relatively high number of false-positive findings. The surgical management of the N0 neck should therefore not be based on PET/CT findings alone.

Tissue Distribution of 18F-FDG-Labeled Peripheral Hematopoietic Stem Cells After Intracoronary Administration in Patients with Myocardial Infarction

Abstract: UNLABELLED Adult stem cell therapy is expected to improve left ventricular function in patients with myocardial infarction. Because of the low risk of arrhythmia and the maximal concentration at the target tissue, intracoronary infusion of stem cells is preferred. The aim of this study was to investigate the homing and tissue distribution of intracoronary injected peripheral hematopoietic stem cells labeled with 18F-FDG. METHODS Seventeen patients with myocardial infarction were included as the intracoronary injection group (14 males, 3 females; age, 58 +/- 12 y). Three patients underwent intravenous stem cell injection as the intravenous injection group (3 males, 0 females; age, 50 +/- 20 y). After mobilization with granulocyte colony-stimulating factor (G-CSF), peripheral stem cells were collected by means of apheresis. 18F-FDG labeling of stem cells was performed for 40 min with gentle intermittent mixing at 37 degrees C. The mean labeling efficiency was 72% (range, 46%-95%), and 44.4-175 MBq (1.2-5 mCi) of 18F-FDG-labeled stem cells were injected via an intracoronary catheter after stenting in infarct-related arteries. PET/CT images were obtained with a 3-dimensional acquisition mode 2 h after intracoronary infusion. RESULTS Two hours after intracoronary infusion, 1.5% (range, 0.2%-3.3%) of injected stem cells accumulated at the infarcted myocardium. Outside of the myocardium, spleen, liver, bladder, and bone marrow showed a high stem cell accumulation. The delayed image of a patient up to 20 h showed a prolonged residence of stem cells at the myocardium. Intravenous injection of stem cells showed a high initial lung uptake with no myocardial activity. CONCLUSION We have shown that 18F-FDG-labeled stem cell PET could be used to assess the tissue distribution and to measure the amount of stem cells at a target tissue. 18F-FDG-labeled stem cell PET can be used to measure and optimize the amount of stem cells injected.

Coronary CT Angiography

Abstract: Advances in multidetector CT (MDCT) technology with submillimeter slice collimation and high temporal resolution permit contrast-enhanced imaging of coronary arteries and coronary plaque during a single breath hold. Appropriate patient preparation, detailed technical and technological knowledge with regard to recognition of typical imaging artifacts (such as beam hardening or motion artifacts), and the adequate choice of postprocessing techniques to detect stenosis and plaque are prerequisites to achieving diagnostic image quality. A growing number of studies have suggested that 64-slice coronary CT angiography is highly accurate for the exclusion of significant coronary artery stenosis (>50% luminal narrowing), with negative predictive values of 97%-100%, in comparison with invasive selective coronary angiography. In addition, several studies have indicated that MDCT also can detect calcified and noncalcified coronary atherosclerotic plaques, especially in proximal vessel segments, showing a good correlation with intracoronary ultrasound. Studies on clinical utility, cost, and cost-effectiveness are now warranted to demonstrate whether and how this technique can change and improve the current management of patients with suspected or confirmed coronary artery disease.

Focal thyroid lesions incidentally identified by integrated 18F-FDG PET/CT: clinical significance and improved characterization.

Abstract: In this retrospective study, we investigated whether the 18F-FDG uptake pattern and CT findings improved the accuracy over the standardized uptake value (SUV) for differentiating benign from malignant focal thyroid lesions incidentally found on 18F-FDG PET/CT. We also defined the prevalence of these lesions and their risk for cancer. Methods:18F-FDG PET/CT was performed on 1,763 subjects without a previous history of thyroid cancer from May 2003 to June 2004. Two nuclear medicine physicians and 1 radiologist interpreted PET/CT images, concentrating on the presence of focal thyroid lesions, the maximum SUV of the thyroid lesion, the pattern of background thyroid 18F-FDG uptake, and the CT attenuation pattern of the thyroid lesion. Results: The prevalence of focal thyroid lesions on PET/CT was 4.0% (70/1,763). Diagnostic confirmation was done on 44 subjects by ultrasonography (US)-guided fine-needle aspiration (n = 29) or US with clinical follow-up (n = 15). Among 49 focal thyroid lesions in these 44 subjects, 18 focal thyroid lesions of 17 subjects were histologically proven to be malignant (papillary cancer in 16, metastasis from esophageal cancer in 1, non–Hodgkin9s lymphoma in 1). Therefore, the cancer risk of focal thyroid lesions was 36.7% on a lesion-by-lesion basis or 38.6% on a subject-by-subject basis. The maximum SUV of malignant thyroid lesions was significantly higher than that of benign lesions (6.7 ± 5.5 vs. 10.7 ± 7.8; P

18F-FDG PET Is an Early Predictor of Pathologic Tumor Response to Preoperative Radiochemotherapy in Locally Advanced Rectal Cancer

Abstract: 18F-FDG PET is a useful tool for assessing the effects of chemo- or radiotherapy. The aim of this study was to correlate the change in tumor 18F-FDG standardized uptake value (SUV) during and after preoperative radiochemotherapy, with the pathologic response achieved in locally advanced rectal cancer (LARC) patients. Methods: Thirty-three patients with LARC underwent total mesorectal excision after preoperative treatment, including 3 cycles of oxaliplatin, raltitrexed, 5-fluorouracil, and folinic acid during pelvic radiotherapy (45 Gy). Staging procedures included endoscopic ultrasound, MRI, and CT. 18F-FDG PET scans were performed at baseline and 12 d after starting radiochemotherapy (intermediate) in all patients. Seventeen patients also had a presurgical scan. For each scan, mean and maximum SUVs were measured. The percentages of SUV decrease from baseline to intermediate (early change) and to presurgical scan (overall change) were assessed and correlated with pathologic response classified as tumor regression grade (TRG). Results: Eighteen tumors (55%) showed complete (TRG1) or subtotal regression (TRG2) and were classified as responders, whereas 15 cases (45%; TRG3 or TRG4) were considered nonresponders. The early median decrease of tumor SUV significantly differed between responders (−62%; range, −44% to −100%) and nonresponders (−22%; range, −2% to −48%). A significant correlation was also found between TRGs and early SUV changes (P

Comparative Evaluation of 18F-FDG PET and 67Ga Scintigraphy in Patients with Sarcoidosis

Abstract: 67Ga scintigraphy has been used for years in sarcoidosis for diagnosis and the extent of the disease. However, little information is available on the comparison of 18F-FDG PET and 67Ga scintigraphy in the assessment of sarcoidosis. The purpose of this study was to compare the uptake of 18F-FDG and 67Ga in the evaluation of pulmonary and extrapulmonary involvement in patients with sarcoidosis. Methods: Eighteen patients with sarcoidosis were examined. 18F-FDG PET was performed at 1 h after injection of 185−200 MBq 18F-FDG. 67Ga whole-body planar and thoracic SPECT images were acquired 72 h after injection of 111 MBq 67Ga. We evaluated 18F-FDG and 67Ga uptake visually and semiquantitatively using standardized uptake values (SUVs) and the ratio of lesion to normal lumbar spine (L/N ratio), respectively. The presence of pulmonary and extrapulmonary lesions was evaluated histopathologically or by the radiologic findings. Results: Five patients had only pulmonary lesions, 12 patients had both pulmonary and extrapulmonary lesions, and 1 patient had only an extrapulmonary lesion. Both 67Ga planar and SPECT images detected 17 of 21 (81%) clinically observed pulmonary sites. The mean ± SD of the L/N ratio was 1.97 ± 1.09. 67Ga planar images detected 15 of 31 (48%) clinically observed extrapulmonary sites. The mean ± SD of the L/N ratio was 1.17 ± 0.33. 18F-FDG PET detected all 21 (100%) clinically observed pulmonary sites. The mean ± SD of the SUV was 7.40 ± 2.48. 18F-FDG PET detected 28 of 31 (90%) clinically observed extrapulmonary sites. The mean ± SD of the SUV was 5.90 ± 2.75. Conclusion: The results of this clinical study suggest that 18F-FDG PET can detect pulmonary lesions to a similar degree as 67Ga scintigraphy. However, 18F-FDG PET appears to be more accurate and contributes to a better evaluation of extrapulmonary involvement in sarcoidosis patients.

SPECT-Guided CT for Evaluating Foci of Increased Bone Metabolism Classified as Indeterminate on SPECT in Cancer Patients

Abstract: Hybridcameras combiningSPECT andspiral CToffertheopportunity to obtain a diagnostic-quality CT image of scintigraphically suggestivelesionsthatdirectlycorrelateswiththeSPECTimage. The field of view of the CT scan can be adapted on the basis of the SPECT findings (‘‘SPECT-guided CT’’). The aim of the presentstudy was to investigate the value of SPECT-guided CT in the assessment of foci of increased bone metabolism classified as indeterminate on SPECT. Methods:Of 272 consecutively examined patients with histologically confirmed malignancy who underwent bone scintigraphy, 112 (41%) required further workup by SPECT because a definite diagnosis could not be established using whole-body planar scintigraphy alone. In 57 of these patients, SPECT was accompanied by inline CT over the body region of interest; the remaining 55 subjects underwent only stand-alone SPECT for logistic reasons. The 57 SPECT/CT studieswere retrospectively evaluated by readers who were unaware of the clinical pretest probability and the findings on the planar scans. In total, 52 lesions in 44 patients were rated as indeterminate on the SPECT images. Afterwards, the corresponding SPECT/CT images were analyzed and the findings previously rated as indeterminate were classified either as definitely benign, indeterminate, or definitely malignant. Results: Of the 52 indeterminate findings on SPECT, 33 (63%) could be correlated with benign findings on CT. These findings involved mostly osteochondrosis, spondylosis, and spondylarthrosis of the spine. Fifteen lesions (29%) could be correlated with osteolysis or sclerotic metastases on CT. Even after analysis of the SPECT/CT images,4lesions (8%) remained indeterminate. These lesions were in the ribs and the scapula. Conclusion: SPECT-guided CT was able to clarify more than 90% of SPECT findings classified as indeterminate in an analysis that was masked as to clinical pretest probability and the planar scanfindings. Further studies carefully

Dosimetry in Peptide Radionuclide Receptor Therapy: A Review

Abstract: The potential of targeted therapy with radiolabeled peptides has been reported in several clinical trials. Although there have been many improvements in dose estimation, a general and reliable dosimetric approach in peptide receptor radionuclide therapy (PRRT) is still a matter of debate. This article reviews the methods for PRRT dosimetry and the results presented in the literature. Radiopharmaceutical characteristics, data processing, dosimetric outcomes, and methods to protect critical organs are reported. The biological effective dose, based on the linear quadratic model, is also described.

Early Tumor Response to Hsp90 Therapy Using HER2 PET: Comparison with 18F-FDG PET

Abstract: We compared 68Ga-DOTA-F(ab′)2-herceptin (DOTA is 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid [HER2 PET]) and 18F-FDG PET for imaging of tumor response to the heat shock protein 90 (Hsp90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17AAG). Methods: Mice bearing BT474 breast tumor xenografts were scanned with 18F-FDG PET and HER2 PET before and after 17AAG treatment and then biweekly for up to 3 wk. Results: Within 24 h after treatment, a significant decrease in HER2 was measured by HER2 PET, whereas 18F-FDG PET uptake, a measure of glycolysis, was unchanged. Marked growth inhibition occurred in treated tumors but became evident only by 11 d after treatment. Thus, Her2 downregulation occurs independently of changes in glycolysis after 17AAG therapy, and Her2 reduction more accurately predicts subsequent tumor growth inhibition. Conclusion: HER2 PET is an earlier predictor of tumor response to 17AAG therapy than 18F-FDG PET.

Analysis of 18F-FET PET for Grading of Recurrent Gliomas: Is Evaluation of Uptake Kinetics Superior to Standard Methods?

Abstract: The aim of the present study was to evaluate whether extended analyses of O-(2-18F-fluoroethyl)-l-tyrosine (FET) uptake kinetics provide results superior to those of standard tumor-to-background ratios in predicting tumor grade in patients with pretreated gliomas. Methods: Dynamic 18F-FET PET studies (0–40 min after injection of 180 MBq of 18F-FET) were performed on 45 glioma patients with suspected tumor recurrence after multimodal treatment. For the standard method, tumoral maximal standardized uptake value (SUVmax) and the ratio to the background were derived from a summed image 20–40 min after injection. Dynamic data evaluation comprised several approaches: first, SUV within a 90% isocontour threshold (SUV90) and the respective ratio to the background calculated for each time frame between 5 and 40 min after injection; second, the time to peak analysis; and third, various parameters accounting for the individual time course of 18F-FET uptake. Results were correlated with the histopathologic findings of MRI/PET-guided stereotactic biopsies and were evaluated with respect to their discriminatory power to separate low- from high-grade tumors using receiver-operating characteristic (ROC) analyses. Results: The parameters taking into account the individual time course of 18F-FET uptake were able to differentiate low-grade from high-grade recurrent astrocytomas with high diagnostic accuracy, reaching the best differentiation with a sensitivity and specificity of 92% and an area under the ROC curve (AUC) of 0.94. For the other parameters, the respective values were considerably lower (time to peak: 85% sensitivity and 88% specificity; SUV90-to-background ratio for single-frame evaluation of the early-uptake phase: 100% sensitivity, 62% specificity, and 0.81 AUC). The lowest performance was provided by the standard method (SUVmax: 73% sensitivity, 54% specificity, and 0.60 AUC; SUVmax-to-background ratio: 62% sensitivity, 62% specificity, and 0.59 AUC). Time–activity curves (5–40 min after injection) slightly and steadily increased in tumor-free patients and in low-grade tumors, whereas high-grade tumors showed an early peak around 10–15 min after injection followed by a decrease. Conclusion: This study has shown differences in the dynamics of 18F-FET uptake between recurrent low- and high-grade gliomas. Therefore, parameters addressing the different kinetic behaviors allow discrimination with high diagnostic power between these 2 prognostically different groups. Thus, the techniques introduced here are clearly superior to the yet most widely used standard method.

Empiric Radioactive Iodine Dosing Regimens Frequently Exceed Maximum Tolerated Activity Levels in Elderly Patients with Thyroid Cancer

Abstract: Although 131I-iodine (RAI) therapy is a mainstay in the treatment of metastatic thyroid cancer, there is controversy regarding the maximum activity that can safely be administered without dosimetric determination of the maximum tolerable activity (MTA). At most institutions, a fixed empiric dosing strategy is often used, with administered activities ranging from 5.55 to 9.25 GBq (150–250 mCi). In our experience with dosimetry, we have observed that this empiric dosing strategy often results in administered RAI activities exceeding the MTA safety limit of 200 cGy (rads) to the blood or bone marrow in many patients with metastatic thyroid cancer. Methods: We retrospectively analyzed 535 hypothyroid dosimetry studies performed as part of routine clinical care in 328 patients with apparently normal renal function. Results: The MTA was less than 5.18 GBq (140 mCi) in 3%, less than 7.4 GBq (200 mCi) in 8%, and less than 9.25 GBq (250 mCi) in 19%. Analysis of MTA values by age at the time of dosimetry revealed little change in the MTA until the age of 70 y, when a significant decrease occurred. An empiric administered activity of 7.4 GBq (200 mCi) would exceed the MTA in 8%−15% of patients less than 70 y old and 22%−38% of patients 70 y old or older. However, administration of 9.25 GBq (250 mCi) would exceed the MTA in 22% of patients less than 70 y old and 50% of patients 70 y old or older. Factors associated with a lowering of MTA to less than 9.25 GBq (250 mCi) were age at dosimetry greater than 45 y, the female sex, subtotal thyroidectomy, and RAI-avid diffuse bilateral pulmonary metastases. Conclusion: Administered RAI activities of less than 5.18 GBq (140 mCi) rarely exposed blood to more than 200 cGy except in the very elderly. However, administered activities of 7.4–9.25 GBq (200–250 mCi) frequently exceeded the calculated MTA in patients 70 y old or older. Therefore, dosimetry-guided RAI therapy may be preferable to fixed-dose RAI treatment strategies in older patients with thyroid cancer and in patients with RAI-avid diffuse bilateral pulmonary metastases, even when renal function is normal.

The 2006 Henry N. Wagner Lecture: Of Mice and Men (and Positrons)—Advances in PET Imaging Technology

Abstract: There have been major advances in PET technology that cumulatively have helped improve image quality, increased the range of applications for PET, and contributed to the more widespread use of PET. Examples of these technologic advances include whole-body imaging, 3-dimensional imaging, new scintillator materials, iterative reconstruction algorithms, combined PET/CT, and preclinical PET. New advances on the immediate horizon include the reintroduction of time-of-flight PET, which takes advantage of the favorable timing properties of newer scintillators; the integration of PET and MRI scanners into a dual-modality imaging system; and the possibility of further significant improvements in spatial resolution in preclinical PET systems. Sensitivity remains a limiting factor in many PET studies. Although, conceptually, huge gains in sensitivity are still possible, realizing these gains is thwarted largely by economic rather than scientific concerns. Predicting the future is fraught with difficulty; nonetheless, it is apparent that ample opportunities remain for new development and innovation in PET technology that will be driven by the demands of molecular medicine, notably sensitive and specific molecular diagnostic tools and the ability to quantitatively monitor therapeutic entities that include small molecules, peptides, antibodies, nanoparticles, DNA/RNA, and cells.