Adjuvant Photodynamic Therapy, Mediated via Topical Versus Systemic Administration of 5‐Aminolevulinic Acid for Control of Murine Mammary Tumor after Surgical Resection

• Published in: Photochemistry and photobiology Vol. 98; no. 1; pp. 117 - 126
• Main Authors: Carter, Shirron, Miller, Joann, Cramer, Gwendolyn, Yuan, Min, Guzman, Stacy, Putt, Mary E., Cengel, Keith A., Freedman, Gary M., Busch, Theresa M.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.01.2022
• Subjects: Administration, Topical; Aminolevulinic acid; Aminolevulinic Acid - pharmacology; Aminolevulinic Acid - therapeutic use; Animals; Breast cancer; Breast Neoplasms - drug therapy; Female; Humans; Leukocytes (neutrophilic); Lumpectomy; Mammary gland; Mice; Photochemotherapy; Photodynamic therapy; Photosensitization; Photosensitizing Agents - pharmacology; Photosensitizing Agents - therapeutic use; Protoporphyrin; Quality of Life; Toxicity; Tumors
• ISSN: 0031-8655; 1751-1097
• DOI: 10.1111/php.13482

Treatment de‐escalation is sought in the management of precursor lesions of early stage breast cancer, driving the appeal of adjuvant modalities to lumpectomy that reduce toxicity and minimally detract from patient quality of life. We investigate photodynamic therapy (PDT), with the photosensitizing prodrug, 5‐aminolevulinic acid (ALA), as adjuvant therapy to complete resection of murine mammary tumor (propagated from TUBO cells). ALA was delivered either systemically (oral, 250 mg kg−1) at 5 h before 632 nm illumination or topically (20% solution) to the resection site at 10 min before light delivery to 135 J cm−2. Treatment with either oral‐ALA‐PDT (oALA‐PDT) or topical‐ALA‐PDT (tALA‐PDT) to the mammary fat pad after TUBO complete resection (CR) produced long‐term tumor control with 90‐day complete response rates of 21% and 32%, respectively, compared to control rates of 0–5% in mice receiving only CR. Thus, CR/tALA‐PDT was equipotent to CR/oALA‐PDT despite ~10‐fold lower levels of ALA‐induced protoporphyrin XI as photosensitizer after topical versus oral‐ALA administration. CR/oALA‐PDT produced more vascular damage, greater proportion of tissue‐resident neutrophils and stronger inflammation when compared to CR/tALA‐PDT. Collectively, these data provide rationale for ongoing investigation of ALA‐PDT as adjuvant therapy after lumpectomy for increased probability of local control in the treatment of breast cancer. TUBO tumors of the murine mammary fat pad received complete resection (CR) followed by adjuvant photodynamic therapy (PDT). CR provided tumor control rates of only 0‐5%. CR followed by PDT with 5‐aminolevulinic acid (ALA) could achieve tumor control with either oral (oALA) or topical (tALA) ALA delivery. CR/oALA‐PDT with a 5 h interval between oALA administration and illumination achieved 21% tumor control. CR/tALA‐PDT with a 10 min topical exposure of the resection site to 20% ALA achieved 32% tumor control. The studies of this report support further investigation of PDT as adjuvant therapy to lumpectomy in treatment of breast cancer.