Improved labelling of no-carrier-added I-123-MIBG and preliminary clinicalevaluation in patients with ventricular arrhythmias

Meta-[I-123]iodobenzylguanidine (I-123-MIBG) is currently used to assess my ocardial sympathetic innervation by single photon emission tomography (SPET ). In recent studies, an enhanced cardiac uptake of I-123-MIBG with high sp ecific activity has been reported, suggesting the clinical potential of no- carrier-added (n.c.a.) I-123-MIBG in the assessment of abnormalities in car diac sympathetic function. This paper describes the preparation of n.c.a. I -123-MIBG by non-isotopic Cu(I)-assisted [I-123]iododebromination and by [I -123]iododestannylation, both resulting in n.c.a. I-123-MIBG with radiochem ical yields of 88 +/- 6% and high specific activity (greater than or equal to 6.3 TBq.mu mol(-1)) in a total synthesis time of less than 50 min. The d iagnostic potential of n.c.a. I-123-MIBG (> 6.3 TBq.mu mol(-1)) was studied in 13 patients (nine patients with malignant ventricular arrhythmias and f our patients suspected of phaeochromocytoma) and compared to commercial I-1 23-MIBG (similar to 75 MBq.mu mol(-1)) using a dual-headed SPET camera (MUL TISPECT II). High specific activity results in higher I-123-MIBG uptake in the heart and in the liver in all patients. The calculated heart-to-lung an d heart-to-liver count ratios 4.5 h post-injection increased by 22 +/- 6% a nd 10 +/- 5% with n.c.a. I-123-MIBG compared to commercial I-123-MIBG respe ctively. In contrast, no significant correlation between the specific activ ity of I-123-MIBG and lung uptake could be established in this study. Analy sis of radioactivity in blood after the intravenous injection of n.c.a. and commercially available I-123-MIBG showed an initial rapid clearance of rad ioactivity from blood, followed by a plateau from 60 min onwards. Within th e first 24 h, more than 85% of the plasma activity was unchanged I-123-MIBG . The free I-123-iodide concentration determined 24 h post-injection was 2 +/- 1% with commercial I-123-MIBG and 3 +/- 2% with n.c.a. I-123-MIBG. In c onclusion, the results of this investigation indicate that n.f.a. I-123-MIB G is a promising clinical tool for imaging myocardial sympathetic dysfuncti on by SPET. High specific activity n.c.a. I-123-MIBG can now be prepared by simple one-step methods giving high radiochemical yields and high purity s uitable for clinical application. This encourages the further clinical vali dation of n.c.a. I-123-MIBG on a large scale. ((C) 1999 Lippincott Williams & Wilkins).