Novel Functional Renal PET Imaging With 18F-FDS in Human Subjects.

The novel PET probe 2-deoxy-2-F-fluoro-D-sorbitol (F-FDS) has demonstrated favorable renal kinetics in animals. We aimed to elucidate its imaging properties in 2 human volunteers. F-FDS was produced by a simple 1-step reduction from F-FDG. On dynamic renal PET, the cortex was delineated and activity gradually transited in the parenchyma, followed by radiotracer excretion. No adverse effects were reported. Given the higher spatiotemporal resolution of PET relative to conventional scintigraphy, F-FDS PET offers a more thorough evaluation of human renal kinetics. Due to its simple production from F-FDG, F-FDS is virtually available at any PET facility with radiochemistry infrastructure.

Rerouting the metabolic pathway of (18)F-labeled peptides: the influence of prosthetic groups.

Current translational cancer research is directed to the development of high affinity peptide ligands for targeting neuropeptide receptors overexpressed in different types of cancer. Besides their desired high binding affinity to the receptor, the suitability of radiolabeled peptides as targeting vectors for molecular imaging and therapy depends on additional aspects such as high tumor-to-background ratio, favorable clearance pattern from nontarget tissue, and sufficient metabolic stability in vivo. This study reports how a switch from the prosthetic group, N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB), to 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) effects the metabolic pathway of an (18)F-labeled bombesin derivative, QWAV-Sar-H-FA01010-Tle-NH2. (18)F-Labeled bombesin derivatives represent potent peptide ligands for selective targeting of gastrin-releasing peptide (GRP) receptor-expressing prostate cancer. Radiosynthesis of (18)F-labeled bombesin analogues [(18)F]FBz-Ava-BBN2 and [(18)F]FDG-AOAc-BBN2 was achieved in good radiochemical yields of ~50% at a specific activity exceeding 40 GBq/µmol. Both nonradioactive compounds FBz-Ava-BBN2 and FDG-AOAc-BBN2 inhibited binding of [(125)I]Tyr(4)-bombesin(1-14) in PC3 cells with IC50 values of 9 and 16 nM, respectively, indicating high inhibitory potency. Influence of each prosthetic group was further investigated in PC3 mouse xenografts using dynamic small animal PET imaging. In comparison to [(18)F]FBz-Ava-BBN2, total tumor uptake levels were doubled after injection of [(18)F]FDG-AOAc-BBN2 while renal elimination was increased. Blood clearance and in vivo metabolic stability were similar for both compounds. The switch from [(18)F]SFB to [(18)F]FDG as the prosthetic group led to a significant reduction in lipophilicity which resulted in more favorable renal clearance and increased tumor uptake. The presented single step radiolabeling-glycosylation approach represents an innovative strategy for site-directed peptide labeling with the short-lived positron emitter (18)F while providing a favorable pharmacokinetic profile of (18)F-labeled peptides.

Combination of biomarkers: PET [18F]flutemetamol imaging and structural MRI in dementia and mild cognitive impairment.

BACKGROUND: The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aß accumulation and neuronal degeneration or injury. OBJECTIVE: It was the aim of this study to compute hippocampus volume from MRI and a neocortical standard uptake value ratio (SUVR) from [(18)F]flutemetamol PET and investigate the performance of these biomarkers when used individually and when combined. METHODS: Fully automated methods for hippocampus segmentation and for computation of neocortical SUVR were applied to MR and scans with the investigational imaging agent [(18)F]flutemetamol in a cohort comprising 27 AD patients, 25 healthy volunteers (HVs) and 20 subjects with amnestic mild cognitive impairment (MCI). Clinical follow-up was performed 2 years after the initial assessment. RESULTS: Hippocampus volumes showed extensive overlap between AD and HV cases while PET SUVRs showed clear group clustering. When both measures were combined, there was a relatively compact cluster of HV scans and a less compact AD cluster. MCI cases had a bimodal distribution of SUVRs. [(18)F]Flutemetamol-positive MCI subjects showed a large variability in hippocampus volumes, indicating that these subjects were in different stages of neurodegeneration. Some [(18)F]flutemetamol-negative MCI scans had hippocampus volumes that were well below the HV range. Clinical follow-up showed that 8 of 9 MCI to AD converters came from the [(18)F]flutemetamol-positive group. CONCLUSION: Combining [(18)F]flutemetamol PET with structural MRI provides additional information for categorizing disease and potentially predicting shorter time to progression from MCI to AD, but this has to be validated in larger longitudinal studies.

18F-FDG PET-TAC en mononucleosis por citomegalovirus / 18F-FDG PET-CT in cytomegalovirus-induced mononucleosis

Mujer de 51 años con fiebre elevada, astenia y pérdida de peso de 3 semanas de evolución. Antecedente de carcinoma de mama y metástasis hepática. La exploración física demostró pequeñas adenopatías no dolorosas en ambas cadenas latero cervicales. El análisis de sangre registró 9.200 leucocitos con 69% de linfocitos y elevación de enzimas hepáticas. Las determinaciones serológicas así como los hemocultivos y urocultivos fueron negativos, siendo únicamente positiva la determinación de IgM anti-CMV. El marcador tumoral CEA estaba ligeramente elevado. Una exploración 18F-FDG PET/TAC demostró adenopatías hipermetabólicas cervicales bilaterales y celiacas, hepatoesplenomegalia e incremento difuso de la captación de 18F-FDG esplénica. Estas alteraciones se relacionaron con la infección por CMV. La evolución de la paciente fue favorable siendo diagnosticada de mononucleosis por CMV. El diagnóstico clínico e inmunológico adecuado de la mononucleosis infecciosa en pacientes mayores de 40 años es importante para evitar procedimientos diagnósticos innecesarios(AU)

The case of a 51 years-old woman with high fever, asthenia and weight loss of three weeks of evolution is presented. She had a personal history of breast cancer and liver metastases. The physical examination showed small painless enlarged lymph nodes in both latero-cervical chains. The blood analysis showed 9200 leukocytes with 69% of lymphocytes and elevated liver enzymes. Serological determinations as well as repeated blood and urine culture were negatives, only the anti-CMV IgM determination being positive. The CEA tumor marker was slightly elevated. PET/CT demonstrated hypermetabolic enlarged lymph nodes in the bilateral cervical chains and in celiac region, hepatosplenomegaly and diffusely increased 18F-FDG uptake in the spleen. These alterations were associated with CMV infection. Her evolution was favorable, and she was diagnosed of CMV mononucleosis. The appropriate clinical and immunological diagnosis of IM in patients aged over 40 years is important to avoid unnecessary diagnostic procedures(AU)

18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial.

OBJECTIVE: The most widely studied positron emission tomography ligand for in vivo beta-amyloid imaging is (11)C-Pittsburgh compound B ((11)C-PIB). Its availability, however, is limited by the need for an on-site cyclotron. Validation of the (18)F-labeled PIB derivative (18)F-flutemetamol could significantly enhance access to this novel technology. METHODS: Twenty-seven patients with early-stage clinically probable Alzheimer disease (AD), 20 with amnestic mild cognitive impairment (MCI), and 15 cognitively intact healthy volunteers (HVs) above and 10 HVs below 55 years of age participated. The primary endpoint was the efficacy of blinded visual assessments of (18)F-flutemetamol scans in assigning subjects to a raised versus normal uptake category, with clinical diagnosis as the standard of truth (SOT). As secondary objectives, we determined the correlation between the regional standardized uptake value ratios (SUVRs) for (18)F-flutemetamol and its parent molecule (11)C-PIB in 20 of the AD subjects and 20 of the MCI patients. We also determined test-retest variability of (18)F-flutemetamol SUVRs in 5 of the AD subjects. RESULTS: Blinded visual assessments of (18)F-flutemetamol scans assigned 25 of 27 scans from AD subjects and 1 of 15 scans from the elderly HVs to the raised category, corresponding to a sensitivity of 93.1% and a specificity of 93.3% against the SOT. Correlation coefficients between cortical (18)F-flutemetamol SUVRs and (11)C-PIB SUVRs ranged from 0.89 to 0.92. Test-retest variabilities of regional SUVRs were 1 to 4%. INTERPRETATION: (18)F-Flutemetamol performs similarly to the (11)C-PIB parent molecule within the same subjects and provides high test-retest replicability and potentially much wider accessibility for clinical and research use.

Glucose transporter protein-independent tumor cell accumulation of fluorine-18-AFDG, a lipophilic fluorine-18-FDG analog.

UNLABELLED: Fluorine-18-fluorodeoxyglucose (FDG) is used clinically for tumor diagnosis, but its mechanism of accumulation in tumor cells is complicated because two factors, glucose transporter protein (GLUT) and hexokinase, govern [18F]FDG uptake directly. We selected a lipophilic [18F]FDG analog, 1,3,4,6-tetra-acetyl-2-[18F]-2-deoxy-D-glucose ([18F]AFDG), to regulate the effects of hexokinase and evaluated its characteristics in an in vitro cell culture system. METHODS: Fluorine-18-AFDG was synthesized by the method used to produce [18F]FDG, as an intermediate of [18F]FDG. Fluorine-18-AFDG uptake study was performed with LS180 tumor cells, and its metabolites were also investigated by thin-layer chromatography. To evaluate the relationship between [18F]AFDG and GLUT, we also examined [18F]AFDG uptake in the presence of cytochalasin B or with increased medium glucose concentration. The effects of lowered temperature (4 degrees C) on [18F]AFDG uptake were also investigated. RESULTS: Fluorine-18-AFDG (lipophilicity: octanol/water = 3.5) uptake was 3.3-fold higher than that of [18F]FDG. Metabolic analysis showed that [18F]AFDG was extremely stable in the incubation medium but was quickly hydrolyzed and metabolized to 2-fluoro-[18F]-2-deoxy-D-glucose-6-phosphate ([18F]FDG-6P) in tumor cells. Fluorine-18-FDG-6P accounted for approximately 45% of the total radioactivity after a 60-min incubation of [18F]AFDG. Incubation with 50 microM cytochalasin B did not affect [18F]AFDG uptake. In medium with double the control glucose level, [18F]FDG uptake was decreased by about 50%, but [18F]AFDG uptake was not affected. Fluorine-18-AFDG uptake and [18F]FDG-6P production did not show saturation and increased linearly with addition of a 10-fold higher concentration of [18F]AFDG. Lowered incubation temperature caused decreased [18F]AFDG uptake due to reduced [18F]FDG-6P production. CONCLUSION: Fluorine-18-AFDG rapidly penetrated the cell membrane as a result of its high lipophilicity and was metabolized to [18F]FDG-6P within cells. Fluorine-18-AFDG was thus characterized as "GLUT-independent [18F]FDG."