Multifunctional Targeted Radiotherapy System for Induced Tumours Expressing Gastrin-releasing Peptide Receptors

The gastrin-releasing peptide receptor (GRP-r) is overexpressed in breast and prostate cancer, and Lys3-bombesin is a peptide that binds with high affinity to the GRP-r. HIV Tat(49-57) is a cell-penetrating peptide that reaches the DNA. In cancer cells,177Lu shows efficient cross-fire effect, while 99mTc that is internalised to cancer cell nuclei acts as an effective system of targeted radiotherapy because of the Auger and IC electron emissions near the DNA. The aim of this research was to prepare a multifunctional system of 177Lu-and 99mTc-labelled gold nanoparticles (AuNPs) that were conjugated to Tat(49-57)-Lys3-bombesin (Tat-BN) and to evaluate the radiation absorbed dose to GRP receptor-positive PC3 tumours that were induced in mice. Cys-Gly-Cys-Tat-BN (CGC-Tat-BN), 1,4,7,10- tetraazacyclododecane-N,N',N'',N'''-tetraacetic-Gly-Gly-Cys (DOTA-GGC) and hydrazinonicotinyl-Phe-Cys-Phe-Trp-Lys-Thr-Cys- Thr-(ol) (HYNIC-TOC) peptides were conjugated to AuNPs to prepare a multifunctional system by means of a spontaneous reaction of the thiol groups of cysteine. TEM, UV-Vis, XPS and Far-IR spectroscopy techniques demonstrated that AuNPs were functionalised with peptides through interactions with the -SH groups. The99mTc labelling was performed via the HYNIC-TOC ligand, and the 177Lu labelling was performed through DOTA-GGC. The radiochemical purity was 96 ± 2%. The 177Lu-absorbed dose per injected activity that was delivered to the PC3 tumours was 7.9 Gy/MBq, and the 99mTc-absorbed dose that was delivered to the nuclei was 0.53 Gy/MBq. The 177Lu/99mTc-AuNP-Tat-BN system showed properties suitable for a targeted radionuclide therapy of tumours expressing GRP receptors due to the energy deposition from β-emissions and the Auger and IC electron emissions near the DNA.