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

J Med Chem. 2022 Dec 22;65(24):16741-16753. doi: 10.1021/acs.jmedchem.2c01586. Epub 2022 Dec 13.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins
  • Animals
  • Boron Compounds / therapeutic use
  • Boron Neutron Capture Therapy* / methods
  • Cell Line, Tumor
  • Iodine Radioisotopes
  • Mice
  • Neoplasms* / diagnostic imaging
  • Neoplasms* / radiotherapy
  • Precision Medicine
  • Tissue Distribution

Substances

  • dodecaborate
  • arginyl-glycyl-aspartic acid
  • Iodine-125
  • Iodine Radioisotopes
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • Boron Compounds
  • Albumins