Showing papers in "European Journal of Nuclear Medicine and Molecular Imaging in 2005"

Brain glucose metabolism in the early and specific diagnosis of Alzheimer's disease. FDG-PET studies in MCI and AD.

Abstract: The demographics of aging suggest a great need for the early diagnosis of dementia and the development of preventive strategies. Neuropathology and structural MRI studies have pointed to the medial temporal lobe (MTL) as the brain region earliest affected in Alzheimer’s disease (AD). MRI findings provide strong evidence that in mild cognitive impairments (MCI), AD-related volume losses can be reproducibly detected in the hippocampus, the entorhinal cortex (EC) and, to a lesser extent, the parahippocampal gyrus; they also indicate that lateral temporal lobe changes are becoming increasingly useful in predicting the transition to dementia. Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) imaging has revealed glucose metabolic reductions in the parieto-temporal, frontal and posterior cingulate cortices to be the hallmark of AD. Overall, the pattern of cortical metabolic changes has been useful for the prediction of future AD as well as in distinguishing AD from other neurodegenerative diseases. FDG-PET on average achieves 90% sensitivity in identifying AD, although specificity in differentiating AD from other dementias is lower. Moreover, recent MRI-guided FDG-PET studies have shown that MTL hypometabolism is the most specific and sensitive measure for the identification of MCI, while the utility of cortical deficits is controversial. This review highlights cross-sectional, prediction and longitudinal FDG-PET studies and attempts to put into perspective the value of FDG-PET in diagnosing AD-like changes, particularly at an early stage, and in providing diagnostic specificity. The examination of MTL structures, which has so far been exclusive to MRI protocols, is then examined as a possible strategy to improve diagnostic specificity. All told, there is considerable promise that early and specific diagnosis is feasible through a combination of imaging modalities.

EANM/ESC procedural guidelines for myocardial perfusion imaging in nuclear cardiology

Abstract: The European procedural guidelines for radionuclide imaging of myocardial perfusion and viability are presented in 13 sections covering patient information, radiopharmaceuticals, injected activities and dosimetry, stress tests, imaging protocols and acquisition, quality control and reconstruction methods, gated studies and attenuation-scatter compensation, data analysis, reports and image display, and positron emission tomography. If the specific recommendations given could not be based on evidence from original, scientific studies, we tried to express this state-of-art. The guidelines are designed to assist in the practice of performing, interpreting and reporting myocardial perfusion SPET. The guidelines do not discuss clinical indications, benefits or drawbacks of radionuclide myocardial imaging compared to non-nuclear techniques, nor do they cover cost benefit or cost effectiveness.

The value of [18F]FDG-PET in the diagnosis of large-vessel vasculitis and the assessment of activity and extent of disease.

Abstract: Purpose This study was performed to investigate the value of 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) in the diagnosis of large-vessel vasculitis and the assessment of activity and extent of disease.

Radiolabelling DOTA-peptides with 68Ga.

Abstract: A new field of interest is the application of 68Ga-labelled DOTA-conjugated peptides for positron emission tomography (PET). The commercially available or house-made generators require time-consuming and tedious handling of the eluate. Radiolabelling at high specific activities without further purification is not possible, while high specific activities are necessary for peptides that potentially display pharmacological side-effects. Here we present the practical aspects and the results of radiolabelling DOTA-peptides with a TiO2-based commercially available 68Ge/68Ga generator. Reaction kinetics and parameters influencing the incorporation of the radionuclide at the highest achievable specific activity were investigated. Since high finger doses were anticipated during handling of the high beta-energy emitter 68Ga, finger dosimetric measurements were performed during radiolabelling and in vivo administration. Fractionated elution of the generator revealed that 80% of the radioactivity was recovered in 1 ml. Bi- and trivalent ionic contaminants that compete for the incorporation of the radionuclide were below 50 nM; thus further tedious and time-consuming purification was avoided. Radiolabelling was performed at pH 3.5–4. Plastic shielding (≥7-mm wall thickness) around the syringe during administration effectively eliminated the positrons. In rats 68GaCl3 had slow clearance from blood, while 68Ga-EDTA was rapidly cleared via the kidneys. Uptake of 68Ga-DOTATOC in somatostatin receptor-positive tissues was high, with no significant difference between 1 and 4 h post injection. DOTA-peptides for PET imaging can be labelled with 68Ga up to specific activities of 1 GBq per nmol within 20 min, enabling the clinical application of peptides that display potential pharmacological side-effects.

Effects of ROI definition and reconstruction method on quantitative outcome and applicability in a response monitoring trial

Abstract: Quantitative measurement of tracer uptake in a tumour can be influenced by a number of factors, including the method of defining regions of interest (ROIs) and the reconstruction parameters used. The main purpose of this study was to determine the effects of different ROI methods on quantitative outcome, using two reconstruction methods and the standard uptake value (SUV) as a simple quantitative measure of FDG uptake. Four commonly used methods of ROI definition (manual placement, fixed dimensions, threshold based and maximum pixel value) were used to calculate SUV (SUV[MAN], SUV15 mm, SUV50, SUV75 and SUVmax, respectively) and to generate “metabolic” tumour volumes. Test–retest reproducibility of SUVs and of “metabolic” tumour volumes and the applicability of ROI methods during chemotherapy were assessed. In addition, SUVs calculated on ordered subsets expectation maximisation (OSEM) and filtered back-projection (FBP) images were compared. ROI definition had a direct effect on quantitative outcome. On average, SUV[MAN], SUV15 mm, SUV50 and SUV75, were respectively 48%, 27%, 34% and 15% lower than SUVmax when calculated on OSEM images. No statistically significant differences were found between SUVs calculated on OSEM and FBP reconstructed images. Highest reproducibility was found for SUV15 mm and SUV[MAN] (ICC 0.95 and 0.94, respectively) and for “metabolic” volumes measured with the manual and 50% threshold ROIs (ICC 0.99 for both). Manual, 75% threshold and maximum pixel ROIs could be used throughout therapy, regardless of changes in tumour uptake or geometry. SUVs showed the same trend in relative change in FDG uptake after chemotherapy, irrespective of the ROI method used. The method of ROI definition has a direct influence on quantitative outcome. In terms of simplicity, user-independence, reproducibility and general applicability the threshold-based and fixed dimension methods are the best ROI methods. Threshold methods are in addition relatively independent of changes in size and geometry, however, and may therefore be more suitable for response monitoring purposes.

Pitfalls of FDG-PET for the diagnosis of osteoblastic bone metastases in patients with breast cancer

Abstract: Purpose The purpose of this study was to investigate the pitfalls of using 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for the evaluation of osteoblastic bone metastases in patients with breast cancer by comparing it with 99mTc-hydroxymethylene diphosphonate bone scintigraphy.

The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate

Abstract: Purpose Gastrointestinal stromal tumours (GIST) are mesenchymal neoplasms of the gastrointestinal tract that are unresponsive to standard sarcoma chemotherapy. Imaging of GIST patients is done with structural and functional methods such as contrast-enhanced helical computed tomography (ceCT) and positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG). The aim of this study was to compare the prognostic power of PET and ceCT and to evaluate the clinical role of PET/CT imaging.

Positron tomographic assessment of androgen receptors in prostatic carcinoma

Abstract: Purpose The purpose of this study was to evaluate the feasibility of androgen receptor (AR) imaging with 16β-[18F]fluoro-5α-dihydrotestosterone (FDHT) by positron emission tomography (PET) and to assess the binding selectivity of FDHT to AR in patients with prostate cancer.

Direct comparison of 18F-FDG and 11C-methionine PET in suspected recurrence of glioma: sensitivity, inter-observer variability and prognostic value

Abstract: 18F-fluorodeoxyglucose (FDG) and 11C-methionine (MET) PET imaging studies allow the investigation of metabolism and amino acid transport in brain tumours. Their (relative) usefulness and prognostic value in suspected recurrence or progression of primary brain tumours after previous therapy is an issue of debate. The aim of this study was to compare directly both radioligands in this setting. Cerebral uptake of FDG and MET was determined sequentially on the same day in 30 patients (21 males, nine females; age 40.4±15.6 years), on average 4.0 years (range 0.1–18) after therapy for a primary brain tumour (23 grade II–IV astrocytomas, four oligodendrogliomas and three mixed oligo-astrocytomas). Images were acquired on a Siemens HR+ dedicated PET camera. Two observers scored FDG and MET scans independently. Semi-quantitative indices defined by the tumour (maximum)-to-background ratio were calculated based on manual ROI delineation and by using MET ROIs for FDG after automated co-registration. Patient follow-up was conducted until the last contact with inconspicuous clinical findings (average 41 months, range 12–62 months after PET) [(n=10)] or until death (n=20). Overall median survival was 15.0 months. MET showed pathologically increased uptake in 28/30 scans, and FDG in 17/30. The inter-observer agreement was 100% for MET and 73% for FDG. Using Kaplan-Meier survival analysis, significant differences were found for both FDG (cut-off 0.8, log-rank p=0.007) and MET (cut-off 2.2, log-rank p=0.014). The combination of FDG and MET information resulted in the highest prognostic accuracy (p=0.003), while MET alone was the best prognostic predictor in the subgroup of patients with primary astrocytoma (n=23). FDG and MET PET studies provide complementary prognostic information in patients with suspected brain tumour recurrence or progression after primary therapy. MET is considered the single agent of choice in the evaluation of these patients because of its sensitivity and clearer delineation of the suspected recurrence.

O-(2-[18F]fluorethyl)-L-tyrosine PET in the clinical evaluation of primary brain tumours.

Abstract: The aim of this study was to evaluate the differential uptake of O-(2-[18F]fluorethyl)-L-tyrosine (FET) in suspected primary brain tumours. Positron emission tomography (PET) was performed in 44 patients referred for the evaluation of a suspected brain tumour. Acquisition consisted of four 10-min frames starting upon i.v. injection of FET. Tumour uptake was calculated as the ratio of maximal tumour intensity to mean activity within a reference region (FETmax). FET uptake above the cortical level was observed in 35/44 lesions. All histologically confirmed gliomas and many other lesions showed FET uptake to a variable extent. No uptake was observed in nine lesions (one inflammatory lesion, one dysembryoplastic neuroepithelial tumour, one mature teratoma, six lesions without histological confirmation). An analysis of uptake dynamics was done in the patients with increased FET uptake (22 gliomas, three lymphomas, three non-neoplastic lesions, three lesions with unknown histology and four other primaries). Upon classification of tumours into low (i.e. WHO I and II) and high grade (i.e. WHO III and IV), a significant difference in FETmax between the two categories was observed only in the first image frame (0–10 min p.i.), with FETmax=2.0 in low-grade and 3.2 in high-grade tumours (p<0.05); no significant differences were found in frame 4 (30–40 min p.i.), with FETmax=2.4 vs 2.7. Similar results were obtained when the analysis was applied only to astrocytic tumours (2.0 vs 3.1 in the first frame; 2.4 vs 2.6 in the fourth frame). These initial results indicate that FET PET is a useful method to identify malignant brain lesions. It appears that high- and low-grade brain tumours exhibit a different uptake kinetics of FET. A kinetic analysis of FET PET may provide additional information in the differentiation of suspected brain lesions.

[18F]3'-deoxy-3'-fluorothymidine PET for the diagnosis and grading of brain tumors.

Abstract: The aim of this study was to evaluate the feasibility of using [18F] 3′-deoxy-3′-fluorothymidine (FLT) positron emission tomography (PET) for the diagnosis and grading of brain tumors.

68Ga-DOTANOC: a first compound for PET imaging with high affinity for somatostatin receptor subtypes 2 and 5.

Abstract: Existing somatostatin-based radiotracers (e.g. In-DOTA TOC) have sole affinity for somatostatin receptor subtype 2 (sst2). This represents a drawback, given that sst1–5 have been shown to be over-expressed in different tumours, alone or concomitantly [1]. Our goal, therefore, was to develop radiopeptides with broader receptor subtype profiles. Ga-DOTANOC is a first compound for PET imaging with high affinity for sst2 and sst5 [2]. Its affinity profile (IC50 nM) for human sst1–5 is, respectively, >10,000, 1.9± 0.4, 40±5.8, 260±74 and 7.2±1.6. For comparison, the values for the standard compound, In-DOTATOC, are >10,000, 4.6±0.2, 120±26, 230±82 and 130±17. Here we present the 60 min p.i. Ga-DOTANOC PET images and the 21 h p.i. In-DOTATOC planar images of a 52-year-old patient with an advanced neuroendocrine tumour. The two examinations were performed within 4 weeks. During this time interval the patient received bisphosphonates. Preparation and application of Ga-DOTANOC PET and Ga-DOTATOC PET are comparable [3]. In the reported case study, the Ga-DOTANOC PET scan shows high radioligand uptake in the liver and bone metastases. Although many bone metastases appeared visually similar in the two scans, the right sixth rib and left occipital bone metastases (arrows) are much more visible on the Ga-DOTANOC PET scan. This selective difference cannot be explained simply by the advantages of the PET technique. The possible predominance of sst5 in these two bone metastases and the high sst5 affinity of GaDOTANOC are in fact the probable reasons for the high Ga-DOTANOC and low In-DOTATOC uptake. The enlarged liver and somatostatin receptor-positive organs such as the spleen (high uptake) and pituitary gland and thyroid (moderate uptake) are also visible. These normal organs, known to express more sst than just sst2, are better visualised with Ga-DOTANOC (see in particular the spleen). We conclude that Ga-DOTANOC is an excellent candidate for primary diagnostic and follow-up investigations in patients with suspected or proven somatostatin receptorpositive tumours. Furthermore, in this case, predictive imaging indicates that Yor Lu-DOTANOC has greater potential for treatment of this patient than Yor LuDOTATOC.

FDG-PET for preoperative staging of bladder cancer.

Abstract: The presence of lymph node involvement (N) and distant metastasis (M) in patients with invasive bladder carcinoma is a major determinant of survival and, therefore, a pivotal element in the therapeutic management. The aim of this prospective study was to evaluate the use of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in this indication. Whole-body FDG-PET and computed tomography (CT) were performed in 55 patients with non-metastatic invasive bladder cancer for preoperative staging. Correlative imaging of PET with CT was performed, leading to a PET(CT) result. The imaging results were compared with the gold standard, consisting of histopathology (lymphadenectomy, guided biopsy) or clinical follow-up for 12 months, and related to overall survival using the Kaplan-Meier method. The gold standard was available in 40 patients and indicated NM-positive disease in 15 patients (12 N lesions, 8 M lesions), and NM-negative disease in 25 patients. For the diagnosis of NM-positive disease, the sensitivity, specificity and accuracy of PET(CT) were 60%, 88% and 78%, respectively. Diagnostic discordances between PET(CT) and CT alone were found in 9/40 patients, among whom PET was correct in six (15%): three with true-positive and one with true-negative distant metastases, and two with true-negative lymph nodes. Median survival time of patients in whom PET(CT) indicated NM-positive disease was 13.5 months, compared with 32.0 months in the patients with a NM-negative PET(CT) (p=0.003). Addition of metabolism-based information provided by FDG-PET to CT in the preoperative staging of invasive bladder carcinoma yields a high diagnostic and prognostic accuracy.

Prostate cancer: a comparative study of 11C-choline PET and MR imaging combined with proton MR spectroscopy

Abstract: Purpose Prostate cancer is difficult to visualise in its early stages using current imaging technology. The present study aimed to clarify the utility of 11C-choline PET for localising and evaluating cancer lesions in patients with prostate cancer by conducting a prospective comparison with magnetic resonance (MR) imaging combined with proton MR spectroscopy.

PET/CT with intravenous contrast can be used for PET attenuation correction in cancer patients.

Abstract: If the CT scan of a combined PET/CT study is performed as a full diagnostic quality CT scan including intravenous (IV) contrast agent, the quality of the joint PET/CT procedure is improved and a separate diagnostic CT scan can be avoided. CT with IV contrast can be used for PET attenuation correction, but this may result in a bias in the attenuation factors. The clinical significance of this bias has not been established. Our aim was to perform a prospective clinical study where each patient had CT performed with and without IV contrast agent to establish whether PET/CT with IV contrast can be used for PET attenuation without reducing the clinical value of the PET scan. A uniform phantom study was used to document that the PET acquisition itself is not significantly influenced by the presence of IV contrast medium. Then, 19 patients referred to PET/CT with IV contrast underwent CT scans without, and then with contrast agent, followed by an 18F-fluorodeoxyglucose whole-body PET scan. The CT examinations were performed with identical parameters on a GE Discovery LS scanner. The PET data were reconstructed with attenuation correction based on the two CT data sets. A global comparison of standard uptake value (SUV) was performed, and SUVs in tumour, in non-tumour tissue and in the subclavian vein were calculated. Clinical evaluation of the number and location of lesions on all PET/CT scans was performed twice, blinded and in a different random order, by two independent nuclear medicine specialists. In all patients, the measured global SUV of PET images based on CT with IV contrast agent was higher than the global activity using non-contrast correction. The overall increase in the mean SUV (for two different conversion tables tested) was 4.5±2.3% and 1.6±0.5%, respectively. In 11/19 patients, focal uptake was identified corresponding to malignant tumours. Eight out of 11 tumours showed an increased SUVmax (2.9±3.1%) on the PET images reconstructed using IV contrast. The clinical evaluation performed by the two specialists comparing contrast and non-contrast CT attenuated PET images showed weighted kappa values of 0.92 (doctor A) and 0.82 (doctor B). No contrast-introduced artefacts were found. This study demonstrates that CT scans with IV contrast agent can be used for attenuation correction of the PET data in combined modality PET/CT scanning, without changing the clinical diagnostic interpretation.

Hybrid SPECT/CT: a new era for SPECT imaging?

Abstract: In recent years the use of medical images in healthcare has grown considerably, mainly due to the rapid evolution of imaging techniques. Now, it is usual for patients to be imaged several times, and a great number of imaging studies are generated. For physicians, it is essential to relate one image to another before rendering an interpretation. Medical images allow the assessment of both the anatomical condition and the functional status of the patient; fusion imaging combines morphological studies with functional ones, thereby overcoming the drawbacks of both modalities and emphasising their individual strengths. In many clinical scenarios, images from different studies are compared by visual analysis, with the observer mentally synthesising the various findings. This intellectual process is very important, but it has been greatly facilitated by the recent development of dual-modality integrated imaging systems (SPECT/CT and PET/CT), which provide functional and anatomical images in the same scanning session, with the acquired images co-registered by means of the hardware [1]. While integrated SPECT/CT applications are not yet so important as those of PET/CT, the first published studies have demonstrated that SPECT/CT can be very useful, because it is able to provide further information of clinical value in several circumstances, and especially in the imaging of tumours. In fact, despite the growing applications of PETand PET/CT in oncology, there is still much that can be done using single-photon emitting radiopharmaceuticals. Currently, more potent SPECT/CT systems are being introduced, incorporating state-of-the-art SPECT with multi-slice CT (up to 16 slices), which allows the acquisition of diagnostic CT images. Until recently, however, only one commercial system with SPECT/CT capability has been available. This hybrid imaging device combines a dual-detector, variable angle gamma camera with a lowdose X-ray tube, attached to the same gantry. This system enables, in a sequential interchangeable sequence, the acquisition, together with SPECT data, of cross-sectional X-ray transmission images, which accurately locate the anatomical sites of radiotracer uptake. The CT data can also be used for attenuation and scatter correction of the emission images [2]. After acquisition, matching emission and transmission data are quickly fused, generating images of SPECT data superimposed on the corresponding anatomical planes. The main drawback of the above-described hybrid device is its low-dose CT scan, which provides low-resolution images that are useful for spatial localisation and fusion with SPECT data but cannot substitute for high-resolution diagnostic CT. Nevertheless, this system is able to provide adequate information for the precise assessment of SPECT findings in most studies. In those cases with insufficient information to permit localisation of a site of radiopharmaceutical uptake, the low-resolution CT images are still useful to define more precisely the appropriate slices to review from a diagnostic quality CT or MR scan, i.e. those slices that match up with the area of interest. Moreover, it is worth noting that the radiation burden due to CT in this device is only about 0.5 mSv, because the X-ray tube operates at 2.5 mA [3]; this aspect is particularly important when a patient has formerly been submitted to a diagnostic CT scan, and it should be taken into due account. When we started working with our SPECT/CT system in 2001, the first question we asked ourselves was whether this hybrid device could be really useful in improving SPECT interpretation. Therefore, to investigate the additional value of SPECT/CT imaging compared with SPECT alone, we began to analyse SPECT images in isolation and then re-evaluated them with the addition of fused images. Based on the results of the first studies performed, we concluded that this new technology can be routinely employed, facilitating the interpretation of SPECT imaging. In fact, in a series of 81 consecutive patients evaluated for various clinical situations, using different radiopharmaceuticals, SPECT/CT improved upon SPECT analysis alone in 41% of cases: it provided correct localisation of SPECT findings in 23 patients, allowed the exclusion of disease at sites of physiological radiotracer uptake in eight cases and defined the functional significance of CT lesions in two patients [4]. These preliminary findings were in accordance with the results of the first clinical paper published on the use of SPECT/CT, which reported a similar improvement in Editorial

11C-methionine PET as a prognostic marker in patients with glioma: comparison with 18F-FDG PET.

Abstract: Purpose The purpose of this study was to compare the prognostic value of 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in glioma patients.

Cancer radioimmunotherapy with alpha-emitting nuclides.

Abstract: In lymphoid malignancies and in certain solid cancers such as medullary thyroid carcinoma, somewhat mixed success has been achieved when applying radioimmunotherapy (RIT) with β-emitters for the treatment of refractory cases. The development of novel RIT with α-emitters has created new opportunities and theoretical advantages due to the high linear energy transfer (LET) and the short path length in biological tissue of α-particles. These physical properties offer the prospect of achieving selective tumoural cell killing. Thus, RIT with α-emitters appears particularly suited for the elimination of circulating single cells or cell clusters or for the treatment of micrometastases at an early stage. However, to avoid non-specific irradiation of healthy tissues, it is necessary to identify accessible tumoural targets easily and rapidly. For this purpose, a small number of α-emitters have been investigated, among which only a few have been used for in vivo preclinical studies. Another problem is the availability and cost of these radionuclides; for instance, the low cost and the development of a reliable actinium-225/bismuth-213 generator were probably determining elements in the choice of bismuth-213 in the only human trial of RIT with an α-emitter. This article reviews the literature concerning monoclonal antibodies radiolabelled with α-emitters that have been developed for possible RIT in cancer patients. The principal radio-immunoconjugates are considered, starting with physical and chemical properties of α-emitters, their mode of production, the possibilities and difficulties of labelling, in vitro studies and finally, when available, in vivo preclinical and clinical studies.

Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent.

Abstract: Purpose The purpose of the study was to evaluate [18F]fluoromisonidazole (FMISO) PET in advanced head and neck cancer during hypoxia-targeting therapy.

Localisation and mechanism of renal retention of radiolabelled somatostatin analogues.

Abstract: Purpose Radiolabelled somatostatin analogues, such as octreotide and octreotate, are used for tumour scintigraphy and radionuclide therapy. The kidney is the most important critical organ during such therapy owing to the reabsorption and retention of radiolabelled peptides. The aim of this study was to investigate in a rat model both the localisation and the mechanism of renal uptake after intravenous injection of radiolabelled somatostatin analogues. The multi-ligand megalin/cubilin receptor complex, responsible for reabsorption of many peptides and proteins in the kidney, is an interesting candidate for renal endocytosis of these peptide analogues.

The uptake of 3′-deoxy-3′-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels

Abstract: The aim of this study was to investigate the role of thymidine kinase 1 (TK1) protein in 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) positron emission tomography (PET) studies. We investigated the in vivo kinetics of [18F]FLT in TK1+/− and TK1−/− L5178Y mouse lymphoma tumours that express different levels of TK1 protein. [18F]FLT-derived radioactivity, measured by a dedicated small animal PET scanner, increased within the tumours over 60 min. The area under the normalised tumour time–activity curve were significantly higher for the TK1+/− compared with the −/− variant (0.89±0.02 vs 0.79±0.03 MBq ml−1 min, P=0.043; n=5 for each tumour type). Ex vivo gamma counting of tissues excised at 60 min p.i. (n=8) also revealed significantly higher tumour [18F]FLT uptake for the TK1+/− variant (6.2±0.6 vs 4.6±0.4%ID g−1, P=0.018). The observed differences between the cell lines with respect to [18F]FLT uptake were in keeping with a 48% higher TK1 protein in the TK1+/− tumours versus the −/− variant (P=0.043). On average, there were no differences in ATP levels between the two tumour variants (P=1.00). A positive correlation between [18F]FLT accumulation and TK1 protein levels (r=0.68, P=0.046) was seen. Normalisation of the data for ATP content further improved the correlation (r=0.86, P=0.003). This study shows that in vivo [18F]FLT kinetics depend on TK1 protein expression. ATP may be important in realising this effect. Thus, [18F]FLT-PET has the potential to yield specific information on tumour proliferation in diagnostic imaging and therapy monitoring.

Primer on molecular imaging technology

Abstract: A wide range of technologies is available for in vivo, ex vivo, and in vitro molecular and cellular imaging. This article focuses on three key in vivo imaging system instrumentation technologies used in the molecular imaging research described in this special issue of Eur J Nucl Med Mol Imaging: positron emission tomography, single-photon emission computed tomography, and bioluminescence imaging. For each modality, the basics of how it works, important performance parameters, and the state-of-the-art instrumentation are described. Comparisons and integration of multiple modalities are also discussed. The principles discussed in this article apply to both human and small animal imaging.

PET imaging of brain with the β-amyloid probe, [11C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer’s disease

Abstract: Purpose The purpose of this study was to evaluate the capacity of [11C]6-OH-BTA-1 and positron emission tomography (PET) to quantify β-amyloid (Aβ) plaques in the Tg2576 mouse model of Alzheimer’s disease (AD).

Imaging DNA synthesis with [18F]FMAU and positron emission tomography in patients with cancer

Abstract: Purpose FMAU (1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)thymine) is a thymidine analog that can be phosphorylated by thymidine kinase and incorporated into DNA. This first-in-human study of [18F]FMAU was conducted as a pilot in patients to determine its biodistribution and suitability for imaging DNA synthesis in tumors using positron emission tomography (PET).

The additional value of PET/CT over PET in FDG imaging of oesophageal cancer

Abstract: Purpose The aim of this study was to assess the value of combined PET/CT compared with PET reviewed side-by-side with CT, in patients with oesophageal cancer, before and after surgery.

Influence of blood glucose level, age and fasting period on non-pathological FDG uptake in heart and gut

Abstract: Purpose Increased, non-pathological FDG uptake in myocardium, stomach and bowel is frequently observed while performing clinical positron emission tomography (PET) studies. This “physiological” increased FDG uptake is not related to (oncological) disease and is unwanted since it may interfere with correct image reading. We evaluated the role of several patient-related factors that may have an influence on this phenomenon.

Physiological 18F-FDG uptake in the ovaries and uterus of healthy female volunteers.

Abstract: Good knowledge of physiological 18F-fluorodeoxglucose (18F-FDG) uptake in the healthy population is of great importance for the correct interpretation of 18F-FDG positron emission tomography (PET) images of pathological processes. The purpose of this study was to investigate the physiological 18F-FDG uptake in the ovaries and uterus of healthy female volunteers. One hundred and 33 healthy females, 78 of whom were premenopausal (age 37.2±6.9 years) and 55 postmenopausal (age 55.0±2.7 years), were examined using whole-body 18F-FDG PET and pelvic magnetic resonance (MR) imaging. Focal 18F-FDG uptake in the ovaries and uterus was evaluated visually and using standardised uptake value (SUVs). Anatomical and morphological information was obtained from MR images. Distinct ovarian 18F-FDG uptake with an SUV of 3.9±0.7 was observed in 26 premenopausal women out of 32 examined during the late follicular to early luteal phase of the menstrual cycle. Eighteen of the 32 women also showed focal 18F-FDG uptake in the endometrium, with an SUV of 3.3±0.3. On the other hand, all nine women in the first 3 days of the menstrual cycle demonstrated intense 18F-FDG uptake in the endometrium, with an SUV of 4.6±1.0. No physiological 18F-FDG uptake was observed in the ovaries or uterus of any postmenopausal women. In women of reproductive age, 18F-FDG imaging should preferably be done within a week before or a few days after the menstrual flow phase to avoid any misinterpretation of pelvic 18F-FDG PET images.

In vivo uptake of [11C]choline does not correlate with cell proliferation in human prostate cancer

Abstract: Purpose Prostate cancer is the second leading cause of death from cancer among US men. Positron emission tomography (PET) with [11C]choline has been shown to be useful in the staging and detection of prostate cancer. The background of the increased uptake of choline in human prostate cancer is not completely understood. The aim of this study was to prospectively investigate the relationship between the [11C]choline uptake and the cell proliferation in human prostate cancer.

18F-FDG PET in children with lymphomas

Abstract: Purpose The aim of this study was to retrospectively evaluate the performance of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) in children with lymphomas, at various stages of their disease.

FDG-PET is able to detect pancreatic carcinoma in chronic pancreatitis

Abstract: 2-(18F)-Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is an imaging technique which enables detection of malignancies. FDG-PET has been established as a tool for the diagnosis of pancreatic carcinoma (CA). Early detection is mandatory as cure can only be achieved in non-advanced disease. This is, however, very difficult with conventional radiological techniques. Patients with chronic pancreatitis (CP) are at risk of developing CA. A simple, reliable screening method for malignant degeneration is highly desirable. We set out to investigate whether FDG-PET is able to detect CA in the setting of CP and can fulfil a potential role in the early detection of CA in CP. FDG-PET was performed in 77 CP patients and in six patients with CP complicated by CA (CP + CA). We included 26 CA patients as a positive control. A positive scan was defined as focal FDG accumulation in the pancreas region. In 67 of the 77 CP (87%) patients, pancreatic FDG accumulation was absent. Six patients had significant accumulation. In CA, 24/26 patients had a positive PET. Five out of the six patients with CP + CA had focal uptake, while minor uptake was seen in one patient. FDG-PET was positive in almost all CA patients and CP + CA patients. FDG-PET was negative in the large majority (87%) of CP patients, which suggests that a positive PET scan in CP patients must lead to efforts to exclude a malignancy. These data suggest that FDG-PET has a potential role as a diagnostic tool for detecting CA in longstanding CP.