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  • Title: Receptor imaging with atrial natriuretic peptide. Part 1: High specific activity iodine-123-atrial natriuretic peptide.
    Author: Lambert R, Willenbrock R, Tremblay J, Bavaria G, Langlois Y, Hogan K, Tartaglia D, Flanagan RJ, Hamet P.
    Journal: J Nucl Med; 1994 Apr; 35(4):628-37. PubMed ID: 8151387.
    Abstract:
    METHODS: Atrial natriuretic peptide (ANP) was labeled in high specific activity using 123I (p,2n). The biodistribution of 123I-ANP was studied in green vervet monkeys by gamma scintigraphy and in rats by dissection and gamma counting. Iodine-125-ANP was also studied in monkeys by in vitro autoradiography. RESULTS: Iodine-123-ANP showed rapid blood clearance with localization to ANP receptors in the kidneys and lungs, which accounted for 35% of total uptake. In vivo competition imaging studies using cold ANP99-126 and C-ANP102-121 proved that uptake is receptor mediated and allowed imaging of the differential biodistribution of A/B and C-ANP receptor families. Thus, it was possible through the use of selective receptor occupation to prevent uptake in certain organs and to effectively steer the labeled ANP to others. The observed biodistribution patterns were confirmed by an in vitro study using 125I-ANP in the same monkeys, which correlated the scintigraphic images with receptor distribution. An in vivo biodistribution study in rats showed a profound effect of specific activity on biodistribution, with a cutoff for receptor uptake at less than 3000 Ci/mmole. CONCLUSION: Gamma scintigraphy with 123I-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 accumulation (%dose/organ approximately 20% or greater) in receptors. The key to receptor imaging with peptides is high specific activity. Labeled ANP offers potential as a diagnostic tool for diabetic nephropathy, particularly for quantifying the involvement of glomerular disease.
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