Assessment of i.p. injection of [18F]fallypride for behavioral neuroimaging in rats.

Great progress has been made toward using small animal PET to assess neurochemical changes during behavior. [(18)F]fallypride (FAL) is a D(2)/D(3) antagonist that is sensitive to changes in endogenous dopamine, and, in theory, could be used to assess changes in dopamine during behavioral paradigms. Tail vein injections of tracer require restraint in awake animals, and catheter implantation is invasive and can cause logistical problems. Thus, administering tracer with i.p. injections (which are well-tolerated by rodents) would be preferable. The purpose of this study was to determine whether i.p. injection of FAL would produce striatal uptake similar to that seen with traditional i.v. tail vein injection protocols. Four male Sprague-Dawley rats underwent i.p. injection of FAL, followed by a 30-min uptake and subsequent dynamic image acquisition on the IndyPET III small animal scanner. Three of these rats also received traditional dynamic scanning with i.v. FAL injection via a tail vein. Two rats that received i.p. injection had moderate striatal uptake, with striatum/cerebellum ratios (SUVR) that were only ∼20% lower than ratios from i.v. scans. Two other rats had little to no uptake; SUVR values were ∼70% lower than i.v. SUVR. These latter two animals showed heavy bone uptake, evidence of defluorination of FAL. The results of this pilot study suggest that it may be possible to achieve striatal uptake of FAL after i.p. injection. However, this was not seen consistently across animals. Future studies are needed to validate, and then to optimize, the use of i.p. FAL for behavioral imaging protocols.

[11C]Choline as a PET biomarker for assessment of prostate cancer tumor models.

[(11)C]Choline has been evaluated as a positron emission tomography (PET) biomarker for assessment of established human prostate cancer tumor models. [(11)C]Choline was prepared by the reaction of [(11)C]methyl triflate with 2-dimethylaminoethanol (DMAE) and isolated and purified by solid-phase extraction (SPE) method in 60-85% yield based on [(11)C]CO(2), 15-20 min overall synthesis time from end of bombardment (EOB), 95-99% radiochemical purity and specific activity >0.8 Ci/micromol at end of synthesis (EOS). The biodistribution of [(11)C]choline was determined at 30 min post iv injection in prostate cancer tumor models C4-2, PC-3, CWR22rv, and LNCaP tumor-bearing athymic mice. The results showed the accumulation of [(11)C]choline in these tumors was 1.0% dose/g in C4-2 mouse, 0.4% dose/g in PC-3 mice, 3.2% dose/g in CWR22rv mice, and 1.4% dose/g in LNCaP mice; the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were 2.3 (T/M, C4-2), 1.4 (T/M, PC-3), 2.5 (T/M, CWR22rv), 1.2 (T/M, LNCaP) and 2.6 (T/B, C4-2), 2.6 (T/B, PC-3), 7.8 (T/B, CWR22rv), 3.2 (T/B, LNCaP), respectively. The micro-PET imaging of [(11)C]choline in prostate cancer tumor models was acquired from a C4-2, PC-3, CWR22rv, or LNCaP implanted mouse at 30 min post iv injection of 1 mCi of the tracer using a dedicated high resolution (<3 mm full-width at half-maximum) small FOV (field-of-view) PET imaging system, IndyPET-II scanner, developed in our laboratory, which showed the accumulation of [(11)C]choline in C4-2, PC-3, CWR22rv, or LNCaP tumor implanted in a nude athymic mouse. The initial dynamic micro-PET imaging data indicated the average T/M ratios were approximately 3.0 (C4-2), 2.1 (PC-3), 3.5 (CWR22rv), and 3.3 (LNCaP), respectively, which showed the tumor accumulation of [(11)C]choline in all four tumor models is high. These results suggest that there are significant differences in [(11)C]choline accumulation between these different tumor types, and these differences might offer some useful measure of tumor biological process.