Showing papers in "Molecular Imaging and Biology in 2007"
TL;DR: About 1/4 of the cortical signal of both [ 11C]NNC 112 and [11C]SCH 23390 is due to binding to 5-HT2A receptors, indicating the need for more selective tracers for the D1 receptor.
Abstract: Purpose: [ 11 C]NNC 112 and [ 11 C]SCH 23390 are selective positron emission tomography (PET) tracers for visualizing dopamine D1 receptors. It is known that both have some affinity for serotonin 2A receptors, but previous studies have suggested this is negligible compared to D1 affinity. We sought to verify this property in vivo. Procedures: Two baboons were scanned to measure the selectivity of both tracers with a displacement paradigm. Four baboons were scanned to directly assess [ 11 C] NNC 112 affinity for both receptors. Results: In vivo ,D 1 to 5-HT2A selectivity is six to fourteenfold, not 100-fold as previously reported by other investigators. Conclusion: We conclude that about 1/4 of the cortical signal of both [ 11 C]NNC 112 and [ 11 C]SCH 23390 is due to binding to 5-HT2A receptors. If confirmed in humans, this suggests caution should be exercised when drawing conclusions from studies using either tracer. These results also indicate the need for more selective tracers for the D1 receptor.
97 citations
TL;DR: Radiation doses delivered during ultrafast micro-CT serial imaging in the mouse are low and are likely below the threshold to affect tumor growth.
Abstract: To determine the radiation dose to mouse cancer xenografts from serial micro-computed tomography (CT) examinations. A nude mouse with a 15-mm subcutaneous pancreatic cancer xenograft in the rightflank was used. Radiation exposure to the subcutaneous tumor and the mouse pancreas (to simulate an orthotopic pancreatic tumor model) was measured using lithium fluoride thermoluminescent dosimeters. Ultrafast micro-CT was performed using 80 kVp, 0.26 mA, 0.156 mm slice thickness, 256 slices, 0.7 mm Al filtration, and 60-second image acquisition time (15 mA second). Micro-CT imaging acquisitions were repeated four times. We measured consistently low tumor doses (0.014 to 0.02 Gy; average = 0.017 Gy) per scan. Orthotopic doses in the region of the pancreas were also consistently low (0.014 to 0.018 Gy; average = 0.016 Gy) per scan. Radiation doses delivered during ultrafast micro-CT serial imaging in the mouse are low and are likely below the threshold to affect tumor growth.
93 citations
TL;DR: Better understanding of physiological uptake throughout the body is valuable for improved interpretive accuracy and should be useful for future semi-automated comparisons to a normal SUV database.
Abstract: The purpose of this study was to map the distribution of 2-deoxy-2-[18F]fluoro-d-glucose (FDG) uptake in organs of patients with no known abnormalities in those tissues. We measured maximum and mean standardized uptake values (SUV) from FDG-positron emission tomography (PET)/computed tomography (CT) obtained from 98 patients (48 males and 50 females). Significant uptake (mean SUVmean > 2.5) was visualized in the cerebellum (8.0 ± 2.2), soft palate (2.92 ± 0.86), palatine tonsils (3.45 ± 1.4), lingual tonsils (3.08 ± 1.05), sublingual glands (3.3 ± 1.5), and testes (2.57 ± 0.56). Negative correlation for FDG uptake versus age was observed for the palatine tonsils, sublingual glands, and lungs (P < 0.001). Better understanding of physiological uptake throughout the body is valuable for improved interpretive accuracy and should be useful for future semi-automated comparisons to a normal SUV database.
87 citations
TL;DR: 60Cu-ATSM hypoxia was correlated with overexpression of VEGF, EGFR, COX-2, CA-9, an increase in apoptosis, and a poor outcome.
Abstract: To determine if hypoxia-related molecular markers are associated with 60Cu labeled diacetyl-bis (N
4-methylthiosemicarbazone); (60Cu-ATSM) imaging of tumor hypoxia in cervical cancer. Fifteen patients were enrolled in a prospective study and underwent evaluation of tumor hypoxia with positron emission tomography (PET) using 60Cu-ATSM. 60Cu-ATSM-PET imaging was compared with the expression of tissue molecular markers, which included vascular endothelial growth factor (VEGF), cyclo-oxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), carbonic anyhdrase IX (CA-9), and apoptotic index. Six patients had hypoxic tumors determined by 60Cu-ATSM, and nine had non-hypoxic tumors. The 4-year overall survival estimates were 75% for patients with non-hypoxic tumors and 33% for those with hypoxic tumors (p = 0.04). Overexpression of VEGF (p = 0.13), EGFR (p = 0.05), CA-9 (p = 0.02), COX-2 (p = 0.08), and the presence of apoptosis (p = 0.005) occurred in patients with hypoxic tumors. Cox proportional hazards modeling demonstrated hypoxia as determined by 60Cu-ATSM to be a significant independent predictor of tumor recurrence (p = 0.0287). 60Cu-ATSM hypoxia was correlated with overexpression of VEGF, EGFR, COX-2, CA-9, an increase in apoptosis, and a poor outcome.
82 citations
TL;DR: FDG-uptake was observed in the majority of clinically inflamed RA joints and in a few OA joints with no significant difference in uptake level, which may be due to secondary synovitis.
Abstract: Purpose
Previous positron emission tomography (PET) studies have shown increased 2-deoxy-2-[18F]fluoro-d-glucose (FDG) uptake in joints of patients with osteoarthritis (OA) and inflamed joints of patients with rheumatoid arthritis (RA). This study compares FDG uptake in joints of RA and OA patients and FDG-uptake with clinical signs of inflammation.
80 citations
TL;DR: A high-yield and fully automated synthesis of [18F]FDDNP—along with the synthesis and characterization of non-radioactive FDDNP, a fluorescent probe derived from 2-(1,1-dicyanopropenyl-2)-6-dimethylaminonaphthalene (DDNP)—are reported.
Abstract: The biomarker 2-(1-{6-[(2-[(18)F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([(18)F]FDDNP) is used as a positron emission tomography (PET) imaging probe for Alzheimer's disease and other neurodegenerative diseases. A high-yield and fully automated synthesis of [(18)F]FDDNP--along with the synthesis and characterization of non-radioactive FDDNP, a fluorescent probe derived from 2-(1,1-dicyanopropenyl-2)-6-dimethylaminonaphthalene (DDNP)--are reported. Radiofluorination of the tosyloxy precursor 2-{[6-(2,2-dicyano-1-methylvinyl)-2-naphthyl](methyl)amino}ethyl-4-methylbenzenesulfonate (DDNPTs) with K(18)F/Kryptofix 2.2.2. yielded chemically (>99%) and radiochemically (>99%) pure [(18)F]FDDNP in high radiochemical yields (40-60%; n> 120), with specific activities ranging from 4 to 8 Ci/mumol at the end of synthesis (90 minutes). Both remote, semiautomated and automated synthesis procedures are described. Either approach provides a reliable method for production of large quantities (110-170 mCi from 500 mCi of [(18)F]fluoride) of [(18)F]FDDNP allowing for multiple PET experiments in the same day or for distribution of the tracer from a single cyclotron facility to PET imaging centers at various geographical distances.
76 citations
TL;DR: Although further optimization of this fusion protein may be needed to improve in vivo performance, the diabody-GLΔ15 is a promising optical imaging probe for tumor detection in vivo.
Abstract: The bioluminescent protein Gaussia luciferase (GLuc) was fused to an anti-carcinoembryonic antigen (CEA) antibody fragment, the diabody, for in vivo optical tumor imaging. A 15-amino acid N-terminal truncation (GLDelta15) resulted in a brighter protein. Fusions of the anti-CEA diabody to full-length GLuc and GLDelta15 retained high affinity for the antigen, emitted light, and exhibited excellent enzymatic stability. In vivo optical imaging of tumor-bearing mice demonstrated specific targeting of diabody-GLDelta15 to CEA-positive xenografts, with a tumor/background ratio of 3.8 +/- 0.4 at four hours after tail-vein injection, compared to antigen-negative tumors at 1.3 +/- 0.1 (p = 0.001). MicroPET imaging using (124)I-diabody-GLDelta15 demonstrated specific uptake in the CEA-positive tumor (2.6% ID [injected dose]/g) compared to the CEA-negative tumor (0.4% ID/g) at 21 hours. Although further optimization of this fusion protein may be needed to improve in vivo performance, the diabody-GLDelta15 is a promising optical imaging probe for tumor detection in vivo.
75 citations
TL;DR: Evidence from positron emission tomography and functional magnetic resonance imaging studies suggests that expectations of symptom improvement are driven by frontal cortical areas, particularly the dorsolateral prefrontal, orbitofrontal, and anterior cingulate cortices.
Abstract: Neuroimaging studies have provided a major contribution to our understanding of the mechanisms of the placebo effect in neurological and psychiatric disorders. Expectation of symptom improvement has long been believed to play a critical role in the placebo effect, and is associated with increased endogenous striatal dopamine release in Parkinson’s disease and increased endogenous opioid transmission in placebo analgesia. Evidence from positron emission tomography and functional magnetic resonance imaging studies suggests that expectations of symptom improvement are driven by frontal cortical areas, particularly the dorsolateral prefrontal, orbitofrontal, and anterior cingulate cortices. The ventral striatum is involved in the expectation of rewarding stimuli and, together with the prefrontal cortex, has also been shown to play an important role in the placebo-induced expectation of therapeutic benefit. Understanding the mechanisms of the placebo effect has important implications for treatment of several medical conditions, including depression, pain, and Parkinson’s disease.
71 citations
TL;DR: P-MRS can be used to study high-energy phosphate metabolites, providing an in vivo assessment of tissue bioenergetic status and the application of these techniques to patients with neurodegenerative disorders, including Parkinson’s disease, Alzheimer's disease, and amyotrophic lateral sclerosis is discussed.
Abstract: Unlike traditional, tracer-based methods of molecular imaging, magnetic resonance spectroscopy (MRS) is based on the behavior of specific nuclei within a magnetic field and the general principle that the resonant frequency depends on the nucleus’ immediate chemical environment. Most clinical MRS research has concentrated on the metabolites visible with proton spectroscopy and measured in specified tissue volumes in the brain. This methodology has been applied in various neurodegenerative disorders, most frequently utilizing measures of N-acetylaspartate as a neuronal marker. At short echo times, additional compounds can be quantified, including myo-inositol, a putative marker for neuroglia, the excitatory neurotransmitter glutamate and its metabolic counterpart glutamine, and the inhibitory neurotransmitter gamma-aminobutyric acid. 31P-MRS can be used to study high-energy phosphate metabolites, providing an in vivo assessment of tissue bioenergetic status. This review discusses the application of these techniques to patients with neurodegenerative disorders, including Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis.
66 citations
TL;DR: This study confirms the good results of FDG-PET/CT for residual/recurrent melanoma detection, as well as for distant metastases localization.
Abstract: 2-Deoxy-2-[F-18]fluoro-d-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is widely available as a powerful imaging modality, combining the ability to detect active metabolic processes and their morphologic features in a single exam. The role of FDG-PET is proven in a variety of cancers, including melanoma, but the estimates of sensitivity and specificity are based in the majority of the published studies on dedicated PET, not PET/CT. Therefore, we were prompted to review our experience with FDG-PET/CT in the management of melanoma. This is a retrospective study on 106 patients with melanoma (20–87 years old; average: 56.8 ± 15.9), who had whole-body FDG-PET/CT at our institution from January 2003 to June 2005. Thirty-eight patients (35.9%) were women and 68 patients (64.1%) were men. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed. All patients had the study for disease restaging. The primary tumor depth (Breslow’s thickness) at initial diagnosis was available for 76 patients (71.7%) and ranged from 0.4 to 25 mm (average: 3.56 mm). The anatomic level of invasion in the skin (Clark’s level) was determined for 70 patients (66%): 3, level II; 13, level III; 43, level IV; 11, level V. The administered dose of 18F FDG ranged from 9.8 to 21.6 mCi (average: 15.4 ± 1.8 mCi). FDG-PET/CT had a sensitivity of 89.3% [95% confidence interval (CI): 78.5–95] and a specificity of 88% (95% CI: 76.2–94.4) for melanoma detection. This study confirms the good results of FDG-PET/CT for residual/recurrent melanoma detection, as well as for distant metastases localization. PET/CT should be an integral part in evaluation of patients with high-risk melanoma, prior to selection of the most appropriate therapy.
62 citations
TL;DR: The extent of presynaptic nigrostriatal dopaminergic denervation can be quantified in PD and may serve as a diagnostic biomarker and dopaminergic receptor imaging may help to distinguish idiopathic PD from atypical parkinsonian disorders.
Abstract: Positron emission tomography (PET) or single photon emission computer tomography (SPECT) imaging provides the means to study neurochemical processes in vivo. These methods have been applied to examine monoaminergic and cholinergic changes in neurodegenerative disorders. These investigations have provided important insights into disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The most intensely studied monoaminergic transmitter is dopamine. The extent of presynaptic nigrostriatal dopaminergic denervation can be quantified in PD and may serve as a diagnostic biomarker. Dopaminergic receptor imaging may help to distinguish idiopathic PD from atypical parkinsonian disorders. Cholinergic denervation has been identified not only in AD but also in PD and more severely in parkinsonian dementia. PET or SPECT can also provide biomarkers to follow progression of disease or evaluate the effects of therapeutic interventions. Cholinergic receptor imaging is expected to play a major role in new drug development for dementing disorders.
TL;DR: The latest applications of brain mapping studies with univariate and multivariate statistical analyses on a voxel basis are reviewed to validate the reproducibility and reliability of unique spatial covariance patterns related with PD and HD.
Abstract: Brain imaging of cerebral blood flow and glucose metabolism has been playing key roles in describing pathophysiology of Parkinson’s disease (PD) and Huntington’s disease (HD), respectively Many biomarkers have been developed in recent years to investigate the abnormality in molecular substrate, track the time course of disease progression, and evaluate the efficacy of novel experimental therapeutics A growing body of literature has emerged on neurobiology of these two movement disorders in resting states and in response to brain activation tasks In this paper, we review the latest applications of these approaches in patients and normal volunteers at rest conditions The discussions focus on brain mapping studies with univariate and multivariate statistical analyses on a voxel basis In particular, we present data to validate the reproducibility and reliability of unique spatial covariance patterns related with PD and HD
TL;DR: PET imaging is sensitive to detect early changes associated with therapy in murine breast cancer models, and a flare reaction was observed 7 days after the initiation of therapy.
Abstract: We used small animal positron emission tomography (PET) imaging to monitor the time-course of tumor metabolic response to hormone and chemotherapy in a murine model of hormone-sensitive breast cancer. Estrogen receptor positive murine mammary carcinomas were inoculated in Balb/c mice. Small animal PET imaging using 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) was used to assess tumor metabolic activity. Imaging was done before and at days 1, 7, and 14 after the administration of doxorubicin, methotrexate, letrozole, or placebo. The tumor uptake of FDG was calculated from a region-of-interest drawn around the tumor. All treatments resulted in a decrease in tumor growth rate and end volume compared to untreated control. FDG uptake was also markedly decreased after treatment although a flare reaction was observed on PET at day 7, the intensity of which varied according to the treatment modality. PET imaging is sensitive to detect early changes associated with therapy in murine breast cancer models. A flare reaction was observed 7 days after the initiation of therapy.
TL;DR: This new experimental in vivo model supports the promise of using FLT- PET, as with FDG-PET, to monitor response to external radiotherapy and warrants further clinical studies to compare these two tracers especially in cancers treated with radiotherapy.
Abstract: Objective
The uptake of 3′-[18F]fluoro-3′-deoxythymidine (FLT), a proliferation marker, was measured before and during fractionated radiotherapy to evaluate the potential of FLT-positron emission tomography (PET) imaging as an indicator of tumor response compared to 2′-deoxy-2′-[18F]fluoro-d-glucose (FDG).
TL;DR: Investigation of the neural basis of motor and cognitive deficits in Parkinson’s disease using anatomical MRI to measure cortical atrophy and functional magnetic resonance imaging suggests that some cognitive deficits are attributable to direct cortical involvement by the disease.
Abstract: For the past 15 years, measurements of cerebral blood flow as an indicator of neuronal activity have been used to gain a better understanding of the neural basis of motor and cognitive deficits in Parkinson’s disease. The initial studies, using positron emission tomography, yielded results in keeping with the hypothesis that symptoms result from excessive cortical inhibition from cortico-striatal loops. However, subsequent studies with functional magnetic resonance imaging (fMRI) have shown that specific aspects of the paradigms used, such as the need to pay attention to one’s movements, have a significant impact on activation patterns, which may complicate the interpretation of results. Functional neuroimaging has also been used to investigate the causes of cognitive impairment in Parkinson’s disease. While some studies implicate dopamine loss in striatum, more recent investigations using anatomical MRI to measure cortical atrophy suggest that some cognitive deficits are attributable to direct cortical involvement by the disease.
TL;DR: FDG-PET provides additional information in a significant fraction of cases (54%) and could be used for restaging of patients with MTC and elevated levels of biomarkers (calcitonin).
Abstract: 2-Deoxy-2-[F-18]fluoro-d-glucose (FDG)-positron emission tomography (PET) has an established role in restaging of various cancers, including papillary and undifferentiated thyroid carcinoma. However, controversies exist regarding its ability to reliably assess recurrent medullary thyroid cancer (MTC). We were therefore prompted to review our experience with FDG-PET for detection of occult MTC. This is a retrospective study (Apr 1, 1997–Mar 31, 2004) of 13 patients with histologic diagnosis of MTC, who had PET examinations. The group included six men and seven women, 15–62 years old (average: 48 ± 13). The PET scan request was triggered by rising levels of calcitonin and negative anatomical imaging studies. Recurrent/metastatic disease was identified by PET in seven (54%) of the 13 patients. The lesions were located in superior mediastinum (4), cervical lymph nodes (3), thyroid bed (2), lung (1) and liver (1). The calcitonin levels ranged from 52 to 5,090 pg/ml (average: 1,996 pg/ml) in patients with negative PET scans and from 132 to 9,500 pg/ml (average: 3,757 pg/ml) in patients with positive studies. The sensitivity and specificity of FDG-PET for disease detection in this cohort were 85.7% (95% CI: 48.7–97.4) and 83.3 % (95 % CI: 43.6–96.9), respectively. Our findings suggest a significant role for FDG-PET in patients with suspected MTC recurrence, with sensitivity of 85.7% and specificity of 83.3% for disease detection. FDG-PET provides additional information in a significant fraction of cases (54%) and could be used for restaging of patients with MTC and elevated levels of biomarkers (calcitonin). Additional studies are necessary to further evaluate the role of FDG-PET in MTC.
TL;DR: Estimation of the individual component of the bone marrow is plausible using medical image segmentation with combined structure–function approach and can have potential research and clinical applications concerning the study of global metabolic activity of theindividual component and diagnosis of benign and malignant bone marrow disorders.
Abstract: Aims
The aim of this study was to introduce a new concept for accurate measurement of the global metabolic activity of the red marrow by combining segmented volumetric data from structural imaging techniques such as magnetic resonance imaging (MRI) and quantitative metabolic information provided by functional modalities such as positron emission tomography (PET).
TL;DR: It is demonstrated that a full kinetic analysis of the FDG kinetics in NSCLC is helpful for the classification into short or long survival and may be used to identify those patients who may benefit from this palliative chemotherapeutic protocol.
Abstract: Introduction
Dynamic positron emission tomography (PET) studies with 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) were performed in patients with advanced nonsmall cell lung cancer (NSCLC) who received palliative chemotherapy to evaluate the impact of full kinetic analysis and assess its value with regard to short or long survival.
TL;DR: It is suggested that FDG metabolic activity of the red marrow in the extremities decline significantly with normal aging, while that of the axial skeleton show minimal decrease related to this biologic phenomenon.
Abstract: The objective of the study was to determine age-related changes occurring in red marrow with regard to its distribution and the degree of its metabolic activity by whole-body 2-deoxy-2-[F-18]fluoro-d-glucose (FDG)-positron emission tomography (PET). This retrospective study included 112 patients (56 male, 56 female, mean age 40 years, range 2–85) who underwent whole-body FDG-PET scans for assessment of disorders that were determined not to affect red marrow activity. These patients were categorized into the following groups with equal gender distribution: 0–15 years (12 individuals), 16–25 years (20), 26–35 years (10), 36–45 years (20), 46–55 years (14), 56–65 years (16), 66–75 years (14), and 76–85 years (6). Whole-body FDG-PET images were performed at 60 min after the intravenous administration of 0.14 mCi/kg of FDG. By employing a dedicated whole-body PET scanner. Maximal standardized uptake value (SUVmax) was calculated from three consecutive transverse sections of the upper thirds of the humeri and femora, manubrium of the sternum, 12th thoracic and 5th lumbar vertebra and anterior superior iliac crests of the pelvis. All available results from other imaging examinations [magnetic resonance imaging (MRI), computed tomography (CT), and conventional radiolography], laboratory data, biopsies, and the clinical course of these subjects were reviewed to make certain that the bone marrow sites examined were free of any known pathologies. SUVmax in the extremities showed significant decline with aging (correlation coefficient of −0.60 to −0.67, p < 0.01). In contrast, a weak correlation was noted in the axial skeletal activity with advancing age (correlation coefficient of −0.28 to −0.48, p < 0.05). These data suggest that FDG metabolic activity of the red marrow in the extremities decline significantly with normal aging, while that of the axial skeleton show minimal decrease related to this biologic phenomenon. These findings are of value in assessing the effects of hematological and other disorders in the distribution and the metabolic activity of this important tissue and testing therapeutic interventions that are employed for treating such maladies.
TL;DR: The literature on the use of PET and MRI in animal models of Parkinson's disease, Huntington’s disease, and Alzheimer's disease is reviewed, and the strengths and limitations of brain imaging inAnimal models of neurodegenerative diseases are evaluated.
Abstract: Animal models have been used extensively to understand the etiology and pathophysiology of human neurodegenerative diseases, and are an essential component in the development of therapeutic interventions for these disorders. In recent years, technical advances in imaging modalities such as positron emission tomography (PET) and magnetic resonance imaging (MRI) have allowed the use of these techniques for the evaluation of functional, neurochemical, and anatomical changes in the brains of animals. Combining animal models of neurodegenerative disorders with neuroimaging provides a powerful tool to follow the disease process, to examine compensatory mechanisms, and to investigate the effects of potential treatments preclinically to derive knowledge that will ultimately inform our clinical decisions. This article reviews the literature on the use of PET and MRI in animal models of Parkinson’s disease, Huntington’s disease, and Alzheimer’s disease, and evaluates the strengths and limitations of brain imaging in animal models of neurodegenerative diseases.
TL;DR: In Parkinson’s disease (PD), there is degeneration of the cholinergic, noradrenergic, and serotonergic systems in addition to dopaminergic projections, and neuronal loss in PD is associated with microglial activation.
Abstract: In Parkinson’s disease (PD), there is degeneration of the cholinergic, noradrenergic, and serotonergic systems in addition to dopaminergic projections. Function of these non-dopaminergic systems can be imaged with positron emission tomography (PET) and single photon emission computed tomography (SPECT) and correlated with motor and nonmotor symptomatology. In addition, neuronal loss in PD is associated with microglial activation. The role of microglia in driving the disease process remains uncertain. This review presents and discusses current findings in these areas.
TL;DR: An early identification of treatment success or failure by molecular imaging could significantly influence patient management by providing more objective decision criteria for evaluation of specific therapeutic strategies and helps to close the gap between in vitro and in vivo integrative biology of disease.
Abstract: As the research on cellular changes has shed invaluable light on the pathophysiology and biochemistry of brain tumors, clinical and experimental use of molecular imaging methods is expanding and allows quantitative assessment. The term molecular imaging is defined as the in vivo characterization and measurement of biologic processes at the cellular and molecular level. Molecular imaging sets forth to probe the molecular abnormalities that are the basis of disease rather than to visualize the end effects of these molecular alterations and, therefore, provides different additional biochemical or molecular information about primary brain tumors compared to histological methods “classical” neuroradiological diagnostic studies. Common clinical indications for molecular imaging contain primary brain tumor diagnosis and identification of the metabolically most active brain tumor reactions (differentiation of viable tumor tissue from necrosis), prediction of treatment response by measurement of tumor perfusion, or ischemia. The interesting key question remains not only whether the magnitude of biochemical alterations demonstrated by molecular imaging reveals prognostic value with respect to survival, but also whether it identifies early disease and differentiates benign from malignant lesions. Moreover, an early identification of treatment success or failure by molecular imaging could significantly influence patient management by providing more objective decision criteria for evaluation of specific therapeutic strategies. Specially, as molecular imaging represents a novel technology for visualizing metabolism and signal transduction to gene expression, reporter gene assays are used to trace the location and temporal level of expression of therapeutic and endogenous genes. Molecular imaging probes and drugs are being developed to image the function of targets without disturbing them and in mass amounts to modify the target’s function as a drug. Molecular imaging helps to close the gap between in vitro and in vivo integrative biology of disease.
TL;DR: In vitro imaging techniques in the neurodegenerative diseases are described as a complement to in vivo positron emission tomography and single photon emission computed tomography imaging.
Abstract: Neurodegeneration induces various changes in the brain, changes that may be investigated using neuroimaging techniques. The in vivo techniques are useful for the visualization of major changes, and the progressing abnormalities may also be followed longitudinally. However, to study and quantify minor abnormalities, neuroimaging of postmortem brain tissue is used. These in vitro methods are complementary to the in vivo techniques and contribute to the knowledge of pathophysiology and etiology of the neurodegenerative diseases. In vitro radioligand autoradiography has given great insight in the involvement of different neuronal receptor systems in these diseases. Data on the dopamine and cholinergic systems in neurodegeneration are discussed in this review. Also, the amyloid plaques are studied using in vitro radioligand autoradiography. Using one of the newer methods, imaging matrix-assisted laser desorption ionization mass spectrometry, the distribution of a large number of peptides and proteins may be detected in vitro on brain cryosections. In this overview, we describe in vitro imaging techniques in the neurodegenerative diseases as a complement to in vivo positron emission tomography and single photon emission computed tomography imaging.
TL;DR: Increased FDG uptake was observed in HCCs that were the least differentiated and correlated with a lower k4 / k3 ratio than the hepatic tissues and were moderately differentiated.
Abstract: Purpose
The Eastern woodchuck (Marmota monax) is considered as a naturally occurring animal model of hepatocellular carcinoma (HCC). The performance of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) for imaging HCC on the woodchuck using Positron emission tomography (PET) was investigated in this study.
TL;DR: These data support the hypothesis that focal hypometabolism involves primarily lateal neocortical rather than mesial temporal structures in ‘MRI-negative PET-positive TLE.’
Abstract: Purpose
Some patients with temporal lobe epilepsy (TLE) lack evidence of hippocampal sclerosis (HS) on MRI (HS-ve). We hypothesized that this group would have a different pattern of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG)-positron emission tomography (PET) hypometabolism than typical mesial TLE/HS patients with evidence of hippocampal atrophy on magnetic resonance imaging (MRI) (HS+ve), with a lateral temporal neocortical rather than mesial focus.
TL;DR: PET tracers aimed at interrogating cholinergic, serotonergic, opiate, benzodiazepine, and inflammatory pathways as well as PET tracers that illuminate amyloid plaques and neurofibrillary tangles in AD are detailed.
Abstract: The symptomatology and known pathology of Alzheimer's disease are restricted to the central nervous system. This review details studies of PET tracers aimed at interrogating cholinergic, serotonergic, opiate, benzodiazepine, and inflammatory pathways as well as PET tracers that illuminate amyloid plaques and neurofibrillary tangles in AD. Progress has been remarkable. Together with studies of brain structure with MRI and of functional regional brain activity, e.g., through measures of blood flow and glucose metabolic rate, molecular imaging promises to dramatically alter our understanding of the structural and physiological abnormalities underlying AD symptomatology. A more immediate impact on the diagnosis and treatment evaluation of AD patients in clinical trials is predicted while the possibility of personalized treatment or prevention of AD may not be that far away.
TL;DR: This paper demonstrates the application of mutual information based coregistration of radionuclide and magnetic resonance imaging (MRI) in an effort to use multimodality imaging for noninvasive localization of stem cells grafted in the infarcted myocardium in rats.
Abstract: This paper demonstrates the application of mutual information based coregistration of radionuclide and magnetic resonance imaging (MRI) in an effort to use multimodality imaging for noninvasive localization of stem cells grafted in the infarcted myocardium in rats. Radionuclide imaging such as single photon emission computed tomography (SPECT) or positron emission tomography (PET) inherently has high sensitivity and is suitable for tracking of labeled stem cells, while high-resolution MRI is able to provide detailed anatomical and functional information of myocardium. Thus, coregistration of PET or SPECT images with MRI will map the location and distribution of stem cells on detailed myocardium structures. To validate this coregistration method, SPECT data were simulated by using a Monte Carlo-based projector that modeled the pinhole-imaging physics assuming nonzero diameter and photon penetration at the edge. Translational and rotational errors of the coregistration were examined with respect to various SPECT activities, and they are on average about 0.50 mm and 0.82 degrees , respectively. Only the rotational error is dependent on activity of SPECT data. Stem cells were labeled with (111)Indium oxyquinoline and grafted in the ischemic myocardium of a rat model. Dual-tracer small-animal SPECT images were acquired, which allowed simultaneous detection of (111)In-labeled stem cells and of [(99m)Tc]sestamibi to assess myocardial perfusion deficit. The same animals were subjected to cardiac MRI. A mutual-information-based coregistration method was then applied to the SPECT and MRIs. By coregistration, the (111)In signal from labeled cells was mapped into the akinetic region identified on cine MRIs; the regional perfusion deficit on the SPECT images also coincided with the akinetic region on the MR image.
TL;DR: RGD-PEG-AdLuc abrogated the native CAR tropism and exhibited significantly enhanced transduction efficiency of integrin-positive tumors than AdLuc through intravenous administration, providing a robust platform for site-specific gene delivery and noninvasive monitoring of the transgene delivery efficacy and homing.
Abstract: Purpose
The goal of this study is to demonstrate the feasibility of chemically modified human adenovirus (Ad) vectors for tumor retargeting.
TL;DR: In this article, the authors quantify sensitivity to W, encourage SUV correction with an approach minimally differing from tradition, and show what improvements in the SUV coefficient of variation (CV) for a population can be expected.
Abstract: Known errors in the standardized uptake value (SUV) caused by variations in subject weights W encountered can be corrected by lean body mass or body surface area (bsa) algorithms replacing W in calculations However this is infrequently done The aims of the work here are: quantify sensitivity to W, encourage SUV correction with an approach minimally differing from tradition, and show what improvements in the SUV coefficient of variation (cv) for a population can be expected Selected for analyses were 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) SUV data from positron emission tomography (PET) and PET/computed tomography (CT) scans at the University of Tennessee as well as from the literature A weight sensitivity index was defined as −n=slope of ln(SUV/W) vs lnW The portion of the SUV variability due to this trend is removed by using the defined $${\text{SUV}}_{n} = {Q \times W^{n} \times W_{{{\text{avg}}}} ^{{1 - n}} } \mathord{\left/ {\vphantom {{Q \times W^{n} \times W_{{{\text{avg}}}} ^{{1 - n}} } {{\text{ID}}}}} \right \kern-
ulldelimiterspace} {{\text{ID}}}$$
, or a virtually equal SUV
m
using $$w = n:{\text{SUV}}_{m} = Q \times {{\left( {wW + {\left( {1 - w} \right)}W_{{{\text{avg}}}} } \right)}} \mathord{\left/ {\vphantom {{{\left( {wW + {\left( {1 - w} \right)}W_{{{\text{avg}}}} } \right)}} {{\text{ID}}}}} \right \kern-
ulldelimiterspace} {{\text{ID}}}$$
, with Q and ID being tissue specific-activity and injected dose $$F = {{\left( {{\text{cv}}\,{\text{of}}\,{\text{SUV}}_{n} \,or\,{\text{of}}\,{\text{SUV}}_{m} } \right)}} \mathord{\left/ {\vphantom {{{\left( {{\text{cv}}\,{\text{of}}\,{\text{SUV}}_{n} \,or\,{\text{of}}\,{\text{SUV}}_{m} } \right)}} {{\left( {{\text{cv}}\,{\text{of}}\,{\text{traditional}}\,{\text{SUV}}} \right)}}}} \right \kern-
ulldelimiterspace} {{\left( {{\text{cv}}\,{\text{of}}\,{\text{traditional}}\,{\text{SUV}}} \right)}}$$
measures performance Adapting to animal studies’ tradition, $${\% W_{m} ID} \mathord{\left/ {\vphantom {{\% W_{m} ID} {wt}}} \right \kern-
ulldelimiterspace} {wt} = 100 \times {\text{SUV}}_{m}$$
is preferred over the conventional $${\% {\text{ID}}} \mathord{\left/ {\vphantom {{\% {\text{ID}}} {wt}}} \right \kern-
ulldelimiterspace} {wt} = 100 \times Q \mathord{\left/ {\vphantom {Q {{\text{ID}}}}} \right \kern-
ulldelimiterspace} {{\text{ID}}}$$
For FDG in adults $$n = w = 044 \pm 003{\left( {{\text{s}}{\text{e}}} \right)}$$
from averaging over most tissues In children, however, $$n = w = 067 \pm 005$$
Tissues have the same index if their influx constants are independent of W Suggested, therefore, is a very simplified $${\text{SUV}}_{m} = Q \times \frac{1}{2}{{\left( {W + W_{{{\text{avg}}}} } \right)}} \mathord{\left/ {\vphantom {{{\left( {W + W_{{{\text{avg}}}} } \right)}} {{\text{ID}}}}} \right \kern-
ulldelimiterspace} {{\text{ID}}}$$
, which is dimensionless and keeps the same population averages as traditional SUVs It achieves $$F = {\left( {{1 - 0011} \mathord{\left/ {\vphantom {{1 - 0011} {{\left( {{\text{cv}}\,{\text{of}}\,{\text{SUV}}} \right)}^{2} }}} \right \kern-
ulldelimiterspace} {{\left( {{\text{cv}}\,{\text{of}}\,{\text{SUV}}} \right)}^{2} }} \right)}^{{1 \mathord{\left/ {\vphantom {1 2}} \right \kern-
ulldelimiterspace} 2}}$$
Hence, for cv’s of SUVs below ∼1/3 improvements over tradition are possible, leading to F’s<095 Accounting additionally for height, as in SUVbsa, gives very little improvement over the simplified approach here and gives essentially the same F’s as SUV
m
Introduced here is a weight index useful in reducing variability and further understanding the SUV Addressing weight sensitivity is appropriate where the cv of the SUVs is below about 1/3 Proposed is the very simple approach of using an average of an adult patient’s weight and ∼70 kg for FDG SUV calculations Unlike other approaches the dimensionless population average of SUV
m
s is unchanged from tradition
TL;DR: Both intercostal muscle and prominent RV uptake in FDG-PET can be associated with a spectrum of causes (including both obstructive and restrictive airway diseases) that lead to breathing exertion and are important markers, which could signify underlying pulmonary disease and pulmonary hypertension.
Abstract: The present study was undertaken to investigate the significance of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) uptake in the intercostal muscles (ICM) and prominent visualization of right ventricle (RV) in FDG-positron emission tomography (PET) scans and its implications. Patients identified to have FDG uptake in the ICM with or without prominent visualization of the RV either incidentally or in the background of an existing explanatory cause at the time of FDG-PET studies were included in this retrospective study. These patients had undergone FDG-PET either for ruling out malignancy or for disease monitoring purposes in setting a proven malignancy. We reviewed the clinical and investigational records (including computed tomography [CT] thorax, chest X-ray, 2-D echo and pulmonary function tests, and arterial blood gas analysis) of the group with incidental FDG uptake for revelation of a pathology explaining such uptake. A total of 14 cases with 16 FDG-PET studies were identified from the retrospective examination of case records. One patient had three FDG-PET at different time points of his disease course. The patient population included 13 males and one female with age range 46–88 years. The patients were classified into two groups: (1) cases with isolated ICM uptake (n = 10); (2) cases with both ICM and RV uptake (n = 4). Among 10 patients with isolated ICM uptake, in six patients it was a serendipitous observation, whereas four patients had existing explanatory cause at the time of FDG-PET. The causes found to be associated included COPD, asthma, recent heart failure, interstitial lung disease (post external radiotherapy) and pulmonary embolism, atelectasis with pleural effusion. In all four cases with associated RV uptake, there was evidence of pulmonary hypertension (PH). Among these, in one patient this was a serendipitous observation. He had evidence of interstitial lung disease (ILD) in CT thorax, and 2-D echo showed moderate PH. The remaining three patients had cor pulmonale secondary to COPD, pneumoconiosis, and Swyer James Syndrome with associated severe PH. The SUVmax ratio of the RV-to-LV free wall ranged from 0.53 to 1.04 in the cases with prominent RV uptake. One patient had multiple FDG-PET studies and have shown reduction of RV uptake in the last scan consistent with the clinical impression of improvement of cor pulmonale. Both intercostal muscle and prominent RV uptake in FDG-PET can be associated with a spectrum of causes (including both obstructive and restrictive airway diseases) that lead to breathing exertion. These are important markers, which could signify underlying pulmonary disease and pulmonary hypertension, respectively. Associated prominent RV uptake strongly indicates presence of pulmonary hypertension and the uptake in the right heart can subserve a valuable surrogate marker in the treatment- monitoring scenario of a known PH.