Photodynamic Therapy Is an Effective Adjuvant Therapy for Image-Guided Surgery in Prostate Cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2020-01, Vol.80 (2), p.156-162
• Main Authors: Wang, Xinning, Ramamurthy, Gopolakrishnan, Shirke, Aditi A, Walker, Ethan, Mangadlao, Joey, Wang, Ziying, Wang, Yu, Shan, Lingpeng, Schluchter, Mark D, Dong, Zhipeng, Brady-Kalnay, Susann M, Walker, Natalie K, Gargesha, Madhusudhana, MacLennan, Gregory, Luo, Dong, Sun, Rongcan, Scott, Bryan, Roy, Debashish, Li, Jing, Basilion, James P
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Surface - metabolism; Antineoplastic Agents - administration & dosage; Cell Line, Tumor; Chemotherapy, Adjuvant - methods; Glutamate Carboxypeptidase II - antagonists & inhibitors; Glutamate Carboxypeptidase II - metabolism; Humans; Injections, Intravenous; Male; Margins of Excision; Mice; Molecular Imaging - methods; Neoplasm Recurrence, Local - pathology; Neoplasm Recurrence, Local - prevention & control; Photochemotherapy - methods; Prostate - diagnostic imaging; Prostate - pathology; Prostate - surgery; Prostatectomy - methods; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; Surgery, Computer-Assisted - methods; Xenograft Model Antitumor Assays
• ISSN: 0008-5472; 1538-7445; 1538-7445
• DOI: 10.1158/0008-5472.CAN-19-0201

Local and metastatic relapses of prostate cancer often occur following attempted curative resection of the primary tumor, and up to 66% of local recurrences are associated with positive margins. Therefore, technologies that can improve the visualization of tumor margins and adjuvant therapies to ablate remaining tumor tissues are needed during surgical resection of prostate adenocarcinoma. Photodynamic agents have the potential to combine both fluorescence for image-guided surgery (IGS) and photodynamic therapy (PDT) to resect and ablate cancer cells. The objective of this study was to determine the utility of a targeted PDT agent for IGS and adjuvant PDT. Using a previously developed prostate-specific membrane antigen (PSMA)-targeted PDT agent, PSMA-1-Pc413, we showed that PSMA-1-Pc413 selectively highlighted PSMA-expressing tumors, allowing IGS and more complete tumor resection compared with white light surgery. Subsequent PDT further reduced tumor recurrence and extended animal survival significantly. This approach also enabled identification of tumor cells in lymph nodes. In summary, this study presents a potential new treatment option for patients with prostate cancer undergoing surgery, which improves tumor visualization and discrimination during surgery, including identification of cancer in lymph nodes. SIGNIFICANCE: These findings present a photodynamic agent that can be used for both photodynamic therapy and image-guided surgery, allowing better visualization of tumor margins and elimination of residual tumor tissues.