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Receptor Imaging with Atrial Natriuretic Peptide Part 1: High Specific Activity Iodine-123-Atrial Natriuretic Peptide

Centre de Recherche, Department of Nuclear Medicine, Department of Surgery, Department of Medicine, Hôtel-Dieu de Montréal, Université de Montréal
Radiopharmaceutical Research and Development, Merck Frosst Canada Inc., Montréal, Québec, Canada

Correspondence: For correspondence or reprints contact: Dr. Pavel Hamet, Centre de Recherche Hôtel Dieu de Montréal, 3850 rue St-Urbain, Pavillon Marie de la Ferre, Montréal, Québec H2W 1T8, Canada.

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 ANP^99-126 and C-ANP^102-121 proved that uptake is receptor mediated and allowed imaging of the differential biodistributlon 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 recaptor 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 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.

Key Words: atrial natriuretic peptide • receptor imaging

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