ECE2015 Oral Communications Adrenal 1 (5 abstracts)
[123/131I] azetidinylamide a novel radiotracer for diagnosis and treatment of adrenocortical tumours -- from bench to bedside
Stefanie Hahner 1 , Britta Heinze 1 , Ken Herrmann 2 , Andreas K Buck 2 , Christina Blümel 2 , Heribert Hänscheid 2 , Joachim Brumberg 2 , David Michelmann 1 , Lukas Nannen 1 , Martin Ries 1 , Martin Fassnacht 1 , Bruno Allolio 1 & Andreas Schirbel 2
1University Hospital Wuerzburg, Dept of Medicine I, Endocrinology and Diabetology, Wuerzburg, Germany; 2University Hospital Wuerzburg, Dept. of Nuclear Medicine, Wuerzburg, Germany.
Background: We have recently introduced [123/131I]iodometomidate (IMTO) which selectively binds to the adrenocortical enzymes aldosterone synthase and 11ß-hydroxylase as SPECT tracer. IMTO has been proven to be useful for molecular adrenal imaging and radiotherapy in adrenal cancer (ACC). As IMTO is rapidly inactivated by endogenous esterases which may impair target tissue to background activity and therapeutic efficacy, >50 new IMTO derivatives have been designed and tested. For the new compound [123/131I] azetidinylamide (IMAZA), comparable inhibition of CYP11B enzyme activity and a higher metabolic stability after incubation with liver microsomes was proven in vitro compared to IMTO.
Methods: IMAZA was subsequently analysed regarding its intracellular uptake in NCI-h295 cells and binding to mitochondrial membranes. In vivo biodistribution of [125I]IMAZA was investigated in CD1 mice. Toxicity testing did not show toxic side effects at standard doses. In four patients with advanced ACC [123I]MAZA or [131I]MAZA was used for diagnostic evaluation of radiotherapy as a treatment option on a compassionate use basis and in three patients dosimetry and therapy was performed. 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 biodistribution experiments in CD1 mice, [125I]IMAZA showed a higher, more selective and longer lasting adrenal uptake compared to [125I]IMTO in vivo. Accordingly, first clinical data show higher metabolic stability in vivo with rapid clearance of unbound tracer. This significantly improved target to background ratios for [123/131I]IMAZA resulting in highly improved imaging quality and calculated tumour doses up to 180 Gy in treated patients.
Conclusion: [123/131I]azetidinylamide is a highly promising radiotracer for molecular adrenal imaging and radiotherapy of adrenocortical carcinoma. The highly specific and lasting uptake in the target tissue lead to superior imaging quality and therapeutic potential compared to IMTO.
Disclosure: This work was supported by the IZKF Wuerzburg (Grant no. F124) and by the Else Kröner-Fesenius Stiftung (Grant no. 2010_EKES.29 and Grant no. 2013_A213).
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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