RGD Peptide-Conjugated Dodecaborate with the Ga-DOTA Complex: A Preliminary Study for the Development of Theranostic Agents for Boron Neutron Capture Therapy and Its Companion Diagnostics.

A boron neutron capture therapy (BNCT) system, using boron-10-introduced agents coupled with companion diagnostics, is anticipated as a promising cancer theranostic. Thus, this study aimed to synthesize and evaluate a probe closo -dodecaborate-(Ga-DOTA)-c(RGDfK) ( 16 ) [Ga = gallium, DOTA =1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, and c(RGDfK) = cyclo(arginine-glycine-aspartate-d-phenylalanine-lysine] containing closo -dodecaborate ([B 12 H 12 ] 2- ) as a boron cluster, a [ 67 Ga]Ga-DOTA derivative for nuclear medicine imaging, and an RGD peptide for tumor targeting. Moreover, we prepared a radioiodinated probe [ 125 I] 17 in which I-125 is introduced into a closo -dodecaborate moiety of 16 . [ 67 Ga] 16 and [ 125 I] 17 showed high stability and high uptake in cancer cells in vitro . Biodistribution experiments in tumor-bearing mice revealed similar biodistribution patterns between [ 67 Ga] 16 and [ 125 I] 17 , such as a high uptake in the tumor and a low uptake in other non-target tissues. Meanwhile, [ 125 I] 17 exhibited higher accumulation in most tissues, including the tumor, than [ 67 Ga] 16 , probably because of higher albumin binding. The higher the [ 125 I] 17 accumulation in the tumor, the more desirable it is for BNCT, with the possibility that the iodo- closo -dodecaborate site may work as an albumin binder.