Targeted Theranostic <sup>111</sup>In/Lu-Nanotexaphyrin for SPECT Imaging and Photodynamic Therapy
Miffy H. Y. Cheng, Marta Overchuk, Maneesha A. Rajora, Jenny W. H. Lou, Ying Chen, Martin G. Pomper, Juen Chen, Gang Zheng
Abstract
Theranostic nanoparticles aim to integrate diagnostic imaging and therapy to facilitate image-guided treatment protocols. Herein, we present a theranostic nanotexaphyrin for prostate-specific membrane antigen (PSMA)-targeted radionuclide imaging and focal photodynamic therapy (PDT) accomplished through the chelation of metal isotopes (In, Lu). To realize nanotexaphyrin’s theranostic properties, we developed a rapid and robust 111In/Lu-nanotexaphyrin radiolabeling method using a microfluidic system that achieved a high radiochemical yield (>90%). The optimized metalated nanotexaphyrin displayed excellent chemical, photo, and colloidal stabilities, potent singlet oxygen generation, and favorable plasma circulation half-life in vivo (t1/2 = 6.6 h). Biodistribution, including tumor accumulation, was characterized by NIR fluorescence, SPECT/CT imaging, and γ counting. Inclusion of the PSMA-targeting ligand enabled the preferential accumulation of 111In/Lu-nanotexaphyrin in PSMA-positive (PSMA+) prostate tumors (3.0 ± 0.3%ID/g) at 48 h with tumor vs prostate in a 2.7:1 ratio. In combination with light irradiation, the PSMA-targeting nanotexaphyrin showed a potent PDT effect and successfully inhibited PSMA+ tumor growth in a subcutaneous xenograft model. To the best of our knowledge, this study is the first demonstration of the inherent metal chelation-driven theranostic capabilities of texaphyrin nanoparticles, which, in combination with PSMA targeting, enabled prostate cancer imaging and therapy.