RECEPTOR IMAGING WITH ATRIAL-NATRIURETIC-PEPTIDE .1. HIGH SPECIFIC ACTIVITY IODINE-123-ATRIAL NATRIURETIC PEPTIDE

Atrial natriuretic peptide (ANP) was labeled in high specific activity using I-123 (p,2n). The biodistribution of I-123-ANP was studied in g reen vervet monkeys by gamma scintigraphy and in rats by dissection an d gamma counting. Iodine-125-ANP was also studied in monkeys by in vit ro autoradiography. Results: Iodine-123-ANP showed rapid blood clearan ce with localization to ANP receptors in the kidneys and lungs, which accounted for 35% of total uptake. In vivo competition imaging studies using cold ANP(99-126) and C-ANP(102-121) proved that uptake is recep tor mediated and allowed imaging of the differential biodistribution o f A/B and C-ANP receptor families. Thus, it was possible through the u se of selective receptor occupation to prevent uptake in certain organ s and to effectively steer the labeled ANP to others. The observed bio distribution patterns were confirmed by an in vitro study using I-125- ANP in the same monkeys, which correlated the scintigraphic images wit h receptor distribution. An in vivo biodistribution study in rats show ed a profound effect of specific activity on biodistribution, with a c utoff for receptor uptake at less than 3000 Ci/mmole. Conclusion: Gamm a scintigraphy with I-123-ANP permits the imaging of ANP receptors in vivo. In contrast to receptor imaging with either organic molecules or antibodies, ANP provides rapid first-pass uptake and substantial accu mulation (% dose/organ approximate to 20% or greater) in receptors. Th e key to receptor imaging with peptides is high specific activity. Lab eled ANP offers potential as a diagnostic tool for diabetic nephropath y, particularly for quantifying the involvement of glomerular disease.