PET imaging of AT₁R with [¹⁸F]FPyKYNE-Losartan: Dosimetry studies in rats

Objectives Hyperactivity of the renin-angiotensin-system (RAS) alters angiotensin II type I receptor (AT₁R) expression. [¹⁸F]FPyKYNE-Losartan exhibited binding selectivity for AT₁R over AT2R in vivo in rat kidneys, and rapid metabolism in rat and pig plasma. This work investigated the biodistribution and radiation dosimetry of [¹⁸F]FPyKYNE-Losartan.

Methods Sprague-Dawley rats injected iv with 0.5 mCi [¹⁸F]FPyKYNE-Losartan were sacrificed at 5, 15, 30 and 60 min after injection (n=6 each). Whole tissues were counted for activity (decay-corrected), weighed and calculated as %ID/g. Radioactivity of carcass was used as the remainder for dosimetry calculations. Residence times (Bq-h/Bq) were obtained by integration of organ activity curves vs. time, then converted into human equivalent values, to obtain effective doses (ED) using ICRP 60 and 103 protocols.

Results Except for gastrointestinal contents and urine which increased over time, rapid uptake of [¹⁸F]FPyKYNE-Losartan was observed in tissues gradually decreasing 5 min following tracer injection. Liver showed the highest uptake (~80% at 5 min and 60-70% by 60 min) and accounted for more than 36% of the ED in both sexes. Thus, the hepatobiliary system and the kidneys are responsible for eliminating [¹⁸F]FPyKYNE-Losartan. Gender averaged ED calculated using ICRP 60 and 103 was 0.030 and 0.031 mSv/MBq, respectively, which is comparable to other ¹⁸F-tracers such as [¹⁸F]FDG. Tissue and whole body dose values are below the 3-5 rem safety limits recommended by the FDA.

Conclusions [¹⁸F]FPyKYNE-Losartan has an acceptable dosimetry profile and is within safe limits for use in human studies. These findings further support its potential application as an AT₁R PET tracer.