A topical fluorescent molecular contrast agent, PARPi-FL (a poly[adenosine diphosphate ribose] polymerase 1 [PARP1] inhibitor–targeted fluorescent contrast agent) detected basal cell carcinoma through intact skin in as little as 5 minutes in ex vivo human tissues, according to new preclinical research published by Ricanati et al in The Journal of Nuclear Medicine. Data confirmed that PARPi-FL is nontoxic to the skin and does not cause systemic side effects, making it a potential tool for the diagnosis and management of basal cell carcinoma.
Basal cell carcinoma is the most common skin cancer, and early treatment typically leads to excellent outcomes. Definitive diagnosis, however, depends on biopsy, which is invasive, can delay diagnosis by weeks to months, and may require patients to return for treatment after histopathologic confirmation.
Emerging nonsurgical therapies for early basal cell carcinomas could be delivered at the bedside, but they require noninvasive diagnostic tools with high accuracy, said co-senior study author Manu Jain, MD, a research pathologist and optical imaging specialist in dermatology at Memorial Sloan Kettering Cancer Center. The new study investigated the feasibility of using fluorescent confocal microscopy with PARPi-FL for enhancing basal cell carcinoma detection in the clinical setting.
Investigators evaluated the optimal dose, application time, and diagnostic performance of PARPi-FL using ex vivo human tissues, including specimens from plastic surgery, Mohs surgery (basal cell carcinomas), and fresh excisions (benign and basal cell carcinomas). They also investigated the feasibility of topical application using gauze and real-time in vivo imaging with a commercial fluorescent confocal microscope device in tumor-bearing mice. Preclinical toxicology studies were conducted to determine safety as well.
A minimal topical dose of 10 μM applied for 2 to 5 minutes via gauze achieved sufficient dermal penetration. PARPi-FL generated a strong fluorescent signal in basal cell carcinoma lesions, with significantly weaker signals in benign tissues, supporting its diagnostic capability. Furthermore, preclinical data confirmed that PARPi-FL was safe for topical application, said co-senior study author Ashish Dhir, PhD, DABT, senior pharmacology and toxicology manager in the Office of Entrepreneurship and Commercialization at Memorial Sloan Kettering Cancer Center.
Incorporating this targeted dye into in vivo imaging could significantly improve diagnostic accuracy; reduce unnecessary biopsies of benign lesions; and enable timely, noninvasive treatment for basal cell carcinoma, noted Dr. Jain. Importantly, since PARP1 is also overexpressed in melanoma, these results support the feasibility of potentially extending this approach to melanoma, offering a promising tool for distinguishing malignant from benign pigmented lesions without biopsy.
Disclosure: For full disclosures of the study authors, visit jnm.snmjournals.org.
