Biodistribution and radiation dosimetry of the PET radiotracer Folate-NOTA-Al-[F-18] in Rhesus monkey.

2016 
1362 Objectives Imaging of the folate receptor (FR) is important for assessing treatment options of patients with FR-expressing cancers, and has been primarily accomplished with the FR-targeting SPECT tracer [Tc-99m]-EC20 (Fisher, et al., 2008). However, clinical PET provides superior spatial resolution, shorter scan times, and greater dynamic imaging capabilities than SPECT. The PET tracer Folate-NOTA-Al-[F-18] has been shown to successfully target FR in vivo (Meng, et al., 2016). In this study, the in vivo biodistribution of Folate-NOTA-Al-[F-18] was compared to [Tc-99m]-EC20, and radiation dosimetry estimates for humans were obtained. Methods Rhesus monkeys (N=3) were scanned with both radiotracers. Monkeys were fasted and maintained under anesthesia with propofol. Following a CT scan, PET data were acquired for 180 minutes following IV administration of Folate-NOTA-Al-[F18] (137-178 MBq, 1.9-2.5 μg), while SPECT data were acquired for 150 min, starting 60 min after administration of [Tc-99m]-EC20 (390-399 MBq, 39-48 μg). Venous blood samples were taken throughout the study and metabolite-corrected blood levels of radiotracer were calculated. Regions of interest (ROI) were drawn for liver, kidney cortex, lumbar spine, lung, small intestine, spleen, bladder, and heart muscle, and average radiotracer uptake from ~60-150 minutes for each ROI was calculated. Absorbed radiation doses were calculated using OLINDA/EXM v1 (Organ Level Internal Dose Assessment) with adult human model inputs. Results PET and SPECT images revealed similar biodistribution for the two radiotracers (Table 1). Based on a mixed-effect model analysis, significant differences in accumulation between radiotracers were detected for spleen, (p= 0.02), heart muscle (p = 0.03), and lumbar spine (p = 0.05). Dosimetry analysis of Folate-NOTA-Al-[F-18] found that the critical organ for males was the testes, while for females the urinary bladder wall was the critical organ. A conservative estimate of the recommended maximum allowable dose of folate-NOTA-Al-[F-18] for clinical research subjects (U.S) is 197 MBq per dose and 328 MBq per year for males, and 235 MBq per dose and 704 MBq per year for females. Conclusions Folate-NOTA-Al-[F-18] showed similar biodistribution to [Tc-99m]-EC20 in Rhesus monkey, and an analysis of radiation dosimetry indicated that human studies will be feasible. These results add support for the PET radiotracer Folate-NOTA-Al-[F-18] as a viable alternative [Tc-99m]-EC20 for FR imaging.
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