Exp Clin Endocrinol Diabetes 2015; 123 - P09_17
DOI: 10.1055/s-0035-1547710

[123/131I](R)-1-[1-(4-iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinylamide (IMAZA) – A novel radiotracer for diagnosis and treatment of adrenocortical tumours – From bench to bedside

B Heinze 1, A Schirbel 2, K Herrmann 3, A Buck 3, C Blümel 3, H Hänscheid 2, D Michelmann 4, L Nannen 4, M Fassnacht 5, B Allolio 6, S Hahner 4
  • 1Universitätsklinikum Würzburg; Medizinische Klinik I; Endokrinologie und Diabetologie
  • 2Universitätsklinikum Würzburg; Department of Nuclear Medicine
  • 3Dept of Nuclear Medicine; University Hospital Würzburg
  • 4Universitätsklinikum Würzburg; Medizinische Klinik I; Endokrinologie und Diabetologie
  • 5Universitätsklinikum Würzburg; Medizinische Klinik I; Schwerpunkt Endokrinologie
  • 6Medizinische Klinik und Poliklinik I; Endokrinologie und Diabetologie; Universitätsklinikum Würzburg

Objective: [123/131I]Iodometomidate (IMTO), which selectively binds to the aldosterone synthase (CYP11B2) and 11ß-hydroxylase (CYP11B1), has been proven to be useful for molecular imaging in adrenal incidentalomas and radiotherapy in adrenocortical carcinoma (ACC). Due to the observation that IMTO is rapidly inactivated by endogenous esterases which may impair target tissue to background activity ratios and accordingly therapeutic efficacy, > 50 new IMTO derivatives have been designed. [123/131I](IMAZA) showed comparable inhibition of CYP11B enzyme activity and a higher metabolic stability after incubation with liver microsomes in vitro compared to IMTO.

Methods: IMAZA was subsequently analysed regarding its intracellular uptake in NCI-h295 cells and binding to mitochondrial membranes. Biodistribution of [125I]IMAZA was investigated in male CD1 mice. In 4 patients with advanced ACC [123I]IMAZA or [131I]IMAZA were used for diagnostic evaluation of radiotherapy as a treatment option on a compassionate use basis. Blood levels of tracer and metabolites were determined by radio-HPLC.

Results: In comparison to [125I]IMTO, [125I]IMAZA demonstrated higher uptake in adrenocortical cells and higher accumulation in the mitochondrial subfraction. In CD1 mice, [125I]IMAZA showed a higher, more selective and longer lasting adrenal uptake compared to [125I]IMTO in vivo. Toxicity testing did not show toxic side effects at standard doses. First clinical data show higher metabolic stability in vivo with rapid clearance of unbound tracer. This significantly improved tumour to background ratios for [123/131I]IMAZA resulting in improved imaging quality and dose ratios of tumour to body up to 5 times higher as compared to IMTO.

Conclusion: [123/131I]IMAZA is a highly promising radiotracer for molecular adrenal imaging and radiotherapy of adrenocortical carcinoma. The highly specific uptake in the target tissue lead to superior imaging quality and therapeutic potential compared to IMTO.