In vivo imaging of insulin receptors by PET: Preclinical evaluation of iodine-125 and iodine-124 labelled human insulin

[A₁₄-*I]iodoinsulin was prepared for studies to assess the suitability of labeled iodoinsulin for positron emission tomography (PET). Iodine-125 was used to establish the methods and for preliminary studies in rats. Further studies and PET scanning in rats were carried out using iodine-124. Tissue and plasma radioactivity was measured as the uptake index (UI = {cpm·(g tissue)^-1}/{cpm injected·(g body weight)^-1}) at 1 to 40 min after intravenous injection of either [A₁₄-¹²⁵I]iodoinsulin or [A₁₄-¹²⁴I]iodoinsulin. For both radiotracers, initial clearance of radioactivity from plasma was rapid (T_1/2 ∼ 1 min), reaching a plateau (UI = 2.8) at ∼ 5 min which was maintained for 35 min. Tissue biodistributions of the two radiotracers were comparable; at 10 min after injection, UI for myocardium was 2.4, liver, 4.0, pancreas, 5.4, brain, 0.17, kidney, 22, lung, 2.3, muscle, 0.54 and fat, 0.28. Predosing rats with unlabelled insulin reduced the UI for myocardium (0.95), liver (1.8), pancreas (1.2) and brain (0.08), increased that for kidney (61) but had no effect on that for lung (2.5), muscle (0.50) or fat (0.34). Analysis of radioactivity in plasma demonstrated a decrease of [¹²⁵I]iodoinsulin associated with the appearance of labeled metabolites; the percentage of plasma radioactivity due to [¹²⁵I]iodoinsulin was 40% at 5 min and 10% at 10 min. The heart, liver and kidneys were visualized using [¹²⁴I]iodoinsulin with PET.