Targeted Theranostic 111In/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

doi:10.1021/acs.molpharmaceut.1c00819

Targeted Theranostic ¹¹¹In/Lu-Nanotexaphyrin for SPECT Imaging and Photodynamic Therapy

Mol Pharm. 2021 Dec 30. doi: 10.1021/acs.molpharmaceut.1c00819. Online ahead of print.

Authors

Miffy H Y Cheng¹, Marta Overchuk¹, Maneesha A Rajora^{1

2}, Jenny W H Lou^{1

3}, Ying Chen⁴, Martin G Pomper⁴, Juen Chen¹, Gang Zheng^{1

2

3}

Affiliations

¹ Princess Margaret Cancer Centre, University Health Network, 101 College Street, PMCRT 5-354, Toronto, Ontario M5G 1L7, Canada.
² Institute of Biomedical Engineering, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada.
³ Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada.
⁴ Johns Hopkins Medical School, 1550 Orleans Street, 492 CRB II, Baltimore, Maryland 21287, United States.

PMID: 34965727
DOI: 10.1021/acs.molpharmaceut.1c00819

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 (t_1/2 = 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.

Keywords: SPECT/CT imaging; indium; lutetium; nanoparticle; photodynamic therapy; texaphyrin-lipid.