title: Triazole Appending Agent (TAAG): A New Synthon for Preparing Iodine-Based Molecular Imaging and Radiotherapy Agents.
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.
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University , 1280 Main Street West, Hamilton, Ontario L8S 4L8, Canada.
authors.forename: Alla
authors.initials: A
authors.lastname: Darwish
authors.affiliation: Centre for Probe Development and Commercialization, McMaster University , 1280 Main Street West Hamilton, Ontario L8S 4K1, Canada.
authors.forename: Megan
authors.initials: M
authors.lastname: Blacker
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University , 1280 Main Street West, Hamilton, Ontario L8S 4L8, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Janzen
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University , 1280 Main Street West, Hamilton, Ontario L8S 4L8, Canada.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Rathmann
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University , 1280 Main Street West, Hamilton, Ontario L8S 4L8, Canada.
authors.forename: Shannon
authors.initials: S
authors.lastname: Czorny
authors.affiliation: Molecular Insight Pharmaceuticals , 160 Second Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Hillier
authors.affiliation: Molecular Insight Pharmaceuticals , 160 Second Street, Cambridge, Massachusetts 02142, United States.
authors.forename: John L
authors.initials: JL
authors.lastname: Joyal
authors.affiliation: Molecular Insight Pharmaceuticals , 160 Second Street, Cambridge, Massachusetts 02142, United States.
authors.forename: John W
authors.initials: JW
authors.lastname: Babich
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University , 1280 Main Street West, Hamilton, Ontario L8S 4L8, Canada.
authors.forename: John F
authors.initials: JF
authors.lastname: Valliant
keywords: SPECT; imaging; iodine; radiochemistry; radiopharmaceuticals