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Proceedings Paper

Long-circulating prostate-specific membrane antigen-targeted NIR phototheranostic agent
Author(s): Marta Overchuk; Kara M. Harmatys; Martha P. F. Damen; Juan Chen; Martin G. Pomper; Gang Zheng
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Paper Abstract

Targeted photodynamic therapy (PDT) combined with image-guided surgical resection is a promising strategy for precision cancer treatment. Targeting the prostate-specific membrane antigen (PSMA) has drawn significant attention due to its marked overexpression in a variety of malignant tissues, most notably in prostate cancer. Recently, we reported the design of a pyropheophorbide-based long-circulating PSMA-targeted phototheranostic agent for multimodal PET/fluorescence imaging and potent PDT of prostate cancer. While this agent is effective in a subcutaneous mouse model, the non-optimal optical properties of pyropheophorbide (Qy absorption maximum at 671 nm) pose a limitation for treatment of deep-seated solid tumors. To further advance PSMA-targeted PDT and enable effective treatment to the deeper layers of tumor tissue, we developed a bacteriochlorophyll-based PSMA-targeted photosensitizer (BPP) which consists of three building blocks: 1) a urea-based PSMA-affinity ligand, 2) a peptide linker to prolong plasma circulation time, and 3) a bacteriochlorophyll photosensitizer for NIR fluorescence imaging (Qy absorption maximum at 750 nm). BPP demonstrated effective cell internalization as well as PDT activity in PSMA-expressing PC3-PIP cells. Furthermore, this agent possesses excellent targeting selectivity in vivo as demonstrated in a dual PSMA-positive and PSMA-negative subcutaneous tumor model. The peptide linker in BPP allowed for its long plasma circulation time (12.65 hours), which enabled its effective tumor accumulation. Overall, bright NIR fluorescence of BPP enables effective image guidance for surgical resection, while the combination of its superb targeting and strong PDT activity allows for potent and precise photodynamic treatment of deep-seated tumors.

Paper Details

Date Published: 7 August 2019
PDF: 6 pages
Proc. SPIE 11070, 17th International Photodynamic Association World Congress, 110704J (7 August 2019); doi: 10.1117/12.2525622
Show Author Affiliations
Marta Overchuk, Princess Margaret Cancer Ctr. (Canada)
Univ. of Toronto (Canada)
Kara M. Harmatys, Princess Margaret Cancer Ctr. (Canada)
Martha P. F. Damen, Princess Margaret Cancer Ctr. (Canada)
Univ. of Amsterdam (Netherlands)
Juan Chen, Univ. of Toronto (Canada)
Martin G. Pomper, Johns Hopkins Medical School (United States)
Gang Zheng, Princess Margaret Cancer Ctr. (Canada)
Univ. of Toronto (Canada)

Published in SPIE Proceedings Vol. 11070:
17th International Photodynamic Association World Congress
Tayyaba Hasan, Editor(s)

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