Triazole Appending Agent (TAAG): A New Synthon for Preparing Iodine-Based Molecular Imaging and Radiotherapy Agents

Alla Darwish; Megan Blacker; Nancy Janzen; Stephanie M Rathmann; Shannon Czorny; Shawn M Hillier; John L Joyal; John W Babich; John F Valliant

doi:10.1021/ml300003v

Triazole Appending Agent (TAAG): A New Synthon for Preparing Iodine-Based Molecular Imaging and Radiotherapy Agents

ACS Med Chem Lett. 2012 Feb 18;3(4):313-6. doi: 10.1021/ml300003v. eCollection 2012 Apr 12.

Authors

Alla Darwish¹, Megan Blacker², Nancy Janzen¹, Stephanie M Rathmann¹, Shannon Czorny¹, Shawn M Hillier³, John L Joyal³, John W Babich³, John F Valliant¹

Affiliations

¹ Department of Chemistry and Chemical Biology, McMaster University , 1280 Main Street West, Hamilton, Ontario L8S 4L8, Canada.
² Centre for Probe Development and Commercialization, McMaster University , 1280 Main Street West Hamilton, Ontario L8S 4K1, Canada.
³ Molecular Insight Pharmaceuticals , 160 Second Street, Cambridge, Massachusetts 02142, United States.

Abstract

A new prosthetic group referred to as the triazole appending agent (TAAG) was developed as a means to prepare targeted radioiodine-based molecular imaging and therapy agents. Tributyltin-TAAG and the fluorous analogue were synthesized in high yield using simple click chemistry and the products labeled in greater than 95% RCY with (123)I. A TAAG derivative of an inhibitor of prostate-specific membrane antigen was prepared and radiolabeled with (123)I in 85% yield where biodistribution studies in LNCap prostate cancer tumor models showed rapid clearance of the agent from nontarget tissues and tumor accumulation of 20% injected dose g(-1) at 1 h. The results presented demonstrate that the TAAG group promotes minimal nonspecific binding and that labeled conjugates can achieve high tumor uptake and exquisite target-to-nontarget ratios.

Keywords: SPECT; imaging; iodine; radiochemistry; radiopharmaceuticals.