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 ([B₁₂H₁₂]^2-) as a boron cluster, a [⁶⁷Ga]Ga-DOTA derivative for nuclear medicine imaging, and an RGD peptide for tumor targeting. Moreover, we prepared a radioiodinated probe [¹²⁵I]17 in which I-125 is introduced into a closo-dodecaborate moiety of 16. [⁶⁷Ga]16 and [¹²⁵I]17 showed high stability and high uptake in cancer cells in vitro. Biodistribution experiments in tumor-bearing mice revealed similar biodistribution patterns between [⁶⁷Ga]16 and [¹²⁵I]17, such as a high uptake in the tumor and a low uptake in other non-target tissues. Meanwhile, [¹²⁵I]17 exhibited higher accumulation in most tissues, including the tumor, than [⁶⁷Ga]16, probably because of higher albumin binding. The higher the [¹²⁵I]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.