⁶⁸Ga-labeled PSMA-targeting carbon nanotubes

Objectives Suitably derivatized inhibitors of prostate-specific membrane antigen (PSMA) provide excellent imaging agents with high target specificity. The goal of this study was to develop carbon nanotube-based agents that can serve as delivery systems for imaging and therapy of PSMA-positive tumors.

Methods Water soluble dextran-modified ultra-short nanotubes (12 groups of dextran/nm) were functionalized with multiple copies of PMSA-targeting ligand. In the first approach we modified nanotubes with urea-linker-DOTA by conjugation through chelating agents. Alternatively, PSMA-targeting ligands and DOTA chelators were attached separately to nanotubes. PSMA-targeting nanotubes were washed out and dialyzed to removed free substrates and analyzed by FT-IR. Radiolabeling with ⁶⁸Ga was performed in 0.5 M NaOAc pH = 4.1 at 95^oC for 15 min (⁶⁸Ge/⁶⁸Ga generator ITG), followed by washout with acetate buffer and analysis using ITLC. ⁶⁹Ga-labeled urea-nanotubes were analyzed using ICP-MS. Radiochemical stability was determined by incubation of washed-out nanotubes in PBS (1X), Ham’s F12 media, and FBS.

Results Modification of nanotubes proceeded in PBS buffer at room temperature using NHS-modified urea or in situ activation of DOTA-urea ligands using EDC and sulfo-NHS and was completed after 12-24h. ⁶⁸Ga-radiolabeling was performed with RCY higher than 98%. In vitro stability of ⁶⁸Ga-radiolabeled nanotube conjugates was greater than 90.1 ± 2.1% intact in PBS and over 81.5 ± 0.7% intact in media at 3 h by iTLC.

Conclusions Nanotube-PSMA inhibitor conjugates were synthesized and labeled with high yield and stability and will be evaluated as imaging agents for PSMA-positive tumors