18f-fluoroethyl-l-tyrosine and alovudine

The radiolabeled amino acid O-(2-(18)F-fluoroethyl)-L-tyrosine (FET) and thymidine analogue 3'-deoxy-3'-(18)F-fluorothymidine (FLT) are widely used for positron emission tomography (PET) brain tumor imaging; however, comparative studies are scarce. The aim of this study therefore was to compare FLT and FET PET for the assessment of anti-VEGF response in glioblastoma xenografts.. Xenografts with confirmed intracranial glioblastoma were treated with anti-VEGF therapy (B20-4.1) or saline as control. Weekly bioluminescence imaging (BLI), FLT and FET PET/CT were used to follow treatment response. Tracer uptake of FLT and FET was quantified using maximum standardized uptake (SUVmax) values and tumor-to-background ratios (TBRs). Survival, the Ki67 proliferation index and micro-vessel density (MVD) were evaluated.. In contrast to FLT TBRs, FET TBRs were significantly lower as early as one week after treatment initiation in the anti-VEGF group as compared to the control group. Following two weeks of treatment, both FLT and FET TBRs were significantly lower in the anti-VEGF group. In contrast, no significant difference between the treatment groups was detected using BLI. Furthermore, we found a significantly lower MVD in the anti-VEGF group as compared to the control group. However, we found no difference in the Ki67 proliferation index or mean survival time.. FET appears to be a more sensitive tracer than FLT to measure early response to anti-VEGF therapy with PET. Advances in knowledge and implications for patient care FET PET appears to be an early predictor of anti-VEGF efficacy. Confirmation of these results in clinical studies is needed.

Topics: Animals; Bevacizumab; Brain Neoplasms; Cell Transformation, Neoplastic; Dideoxynucleosides; Female; Glioblastoma; HEK293 Cells; Humans; Mice; Microvessels; Positron-Emission Tomography; Survival Analysis; Tyrosine; Vascular Endothelial Growth Factor A

Diagnostic investigations with positron-emitting radiopharmaceuticals are dominated by (18)F-fluorodeoxyglucose ((18)F-FDG), but other radiopharmaceuticals are also commercially available or under development. Five of them, which are all clinically important, are (18)F-fluoride, (18)F-fluoroethyltyrosine ((18)F-FET), (18)F-deoxyfluorothymidine ((18)F-FLT), (18)F-fluorocholine ((18)F-choline) and (11)C-raclopride. To estimate the potential risk of stochastic effects (mainly lethal cancer) to a population, organ doses and effective dose values were updated for all five radiopharmaceuticals. Dose calculations were performed using the computer program IDAC2.0, which bases its calculations on the ICRP/ICRU adult reference voxel phantoms and the tissue weighting factors from ICRP publication 103. The biokinetic models were taken from ICRP publication 128. For organ doses, there are substantial changes. The only significant change in effective dose compared with previous estimations was a 46 % reduction for (18)F-fluoride. The estimated effective dose in mSv MBq(-1) was 1.5E-02 for (18)F-FET, 1.5E-02 for (18)F-FLT, 2.0E-02 for (18)F-choline, 9.0E-03 for (18)F-fluoride and 4.4E-03 for (11)C-raclopride.

Topics: Carbon Isotopes; Choline; Dideoxynucleosides; Female; Fluorodeoxyglucose F18; Humans; Kinetics; Male; Phantoms, Imaging; Positron-Emission Tomography; Raclopride; Radiation Dosage; Radiometry; Radiopharmaceuticals; Software; Stochastic Processes; Tyrosine

Multiple sclerosis (MS) is a heterogeneous disease with respect to lesion pathology, course of disease, and treatment response. Imaging modalities are needed that allow better definition of MS lesions in vivo. The aim of this study was to establish an MRI- and PET/CT-based imaging modality and to evaluate approved and promising PET tracers in experimental autoimmune encephalomyelitis (EAE), the animal model of MS.. MRI and PET/CT scans were obtained in Dark agouti rats with EAE and healthy control rats. The PET tracers 2-(18)F-fluoro-2-deoxy-d-glucose ((18)F-FDG), 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), and O-(2-(18)F-fluoro-ethyl)-l-tyrosine ((18)F-FET) were used as surrogate markers of glucose utilization, proliferative activity, and amino acid transport and protein biosynthesis. Immediately after the PET/CT scan, animals were sacrificed for autoradiography, histologic work-up, or RNA expression analysis.. EAE lesions were predominantly located in the spinal cord. With MRI, we were able to detect inflammatory lesions in diseased rats, which correlated well with inflammatory infiltrates as determined by histology. Increased (18)F-FDG uptake was observed in spinal cord lesions in all diseased rats. Further investigation by volume-of-interest analysis demonstrated a correlation between the density of histologically proven cellular infiltrates and the (18)F-FDG signal intensity in PET (F(DF=3) = 5.9, P = 0.001) and autoradiography (F(DF=3) = 4.2, P = 0.008). With (18)F-FET and (18)F-FLT, no definite uptake could be observed on PET scans, whereas autoradiography showed slight radiotracer accumulation in some lesions.. Spinal cord inflammatory lesions in the EAE model can be noninvasively visualized in vivo using MRI and (18)F-FDG PET/CT. Localized (18)F-FDG uptake correlates better with a histologically proven abundance of inflammatory cells as a critical marker of disease activity than MRI. Neither (18)F-FET nor (18)F-FLT seems to be a suitable marker for the in vivo detection of inflammatory lesions.

Topics: Animals; Cell Proliferation; Dideoxynucleosides; Encephalomyelitis, Autoimmune, Experimental; Female; Fluorodeoxyglucose F18; Inflammation; Positron-Emission Tomography; Rats; Spinal Cord; Tyrosine