TAT-10: Development of Alpha-emitting At111-meta-astotbenzylguanidine (At211-MABG) as a Novel Therapeutic Agent for Malignant Pheochromocytoma

Kanazawa, Japan (UroToday.com) Malignant pheochromocytoma (PCC) has previously been treated with the beta-emitter I131 conjugated to meta-iodobenzylguanidine with only limited success since complete remission was quite low. This motivates the present study with alpha-emitting At211-MABG.

Both in vivo and in vitro studies were conducted with a rat cell line, PC12. PC12 uptake of At211-MABG was high and clonogenic growth was significantly (P<0.0001) suppressed with a single treatment of dose 0.2 kBq/ml. DNA double-strand breaks, cell cycle arrest at G2/M phase and cell death were all observed. In vivo studies biodistribution studies showed good tumor distribution and retention (29 +/- 9 % injected dose per gram of tissue (%ID/g) at 1 hour and 16 +/-6% %ID/g at 24 hours post injection. A single injection of At211-MABG (555 kBq/head) showed significant (P<0.01) tumor size reduction: relative volume at day 7 of  0.54 +/- 0.12 versus 1.86 +/- .60 % for the control group.

Side effects were tolerable. Radioactivity in normal organs (excepting adrenal and stomach) was timely cleared. No significant (P=0.881) weight reduction was observed at day 7.

Although dose-escalation studies remain, our data indicate that At211-MABG is a promising therapeutic agent for PCC.

Presented By: Yasuhiro Ohshima from Quantum Beam Science Research Directorate, National Institute for Quantum and Radiological Science and Technology, Takasaki, Japan

Written By: William Carithers, Lawrence Berkeley National Laboratory

at the 10th International Symposium on Targeted Alpha Therapy (TAT-10)  May 31 - June 1, 2017 - Kanazawa, Japan.
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