Abstract P2-01-20: The non-invasive treatment for sentinel lymph node metastasis by photodynamic therapy using a verteporfin solubilized phospholipid polymer aggregate
Authors: K Shimada, S Matsuda, H Jinno, T Konno, A Ito, T Arai, K Ishihara, Y Kitagawa
Journal: Cancer Research (2017)

Abstract Introduction: Sentinel lymph node biopsy (SLNB) has become a standard procedure for axillary lymph node evaluation in clinically node-negative breast cancer patients. Recent trial suggested that patients with 1or 2 sentinel lymph nodes (SLNs) involvement could be treated with SLNB alone. Although SLNB is much less invasive procedure comparing with axillary lymph node dissection (ALND), it is still associated with complications such as lymph edema, numbness and pain. Photodynamic therapy (PDT) against cancer is a non-invasive optical therapeutic method in which the topical or systemic delivery of photosensitizing drugs is followed by its subsequent activation with broadband red light. In this study, the usefulness of PDT for treating SLN metastasis was evaluated in murine model. Materials and Methods: Verteporfin, a hydrophobic photosensitizer (PS) forms a soluble conjugate in aqueous medium with a water-soluble and amphiphilic PMB polymer as a solubilizer. The PMB forms stable and well-dispersed molecular aggregate when its concentration is over 1.0 mg/mL based on the hydrophobic interactions among polymer chains. The verteporfin can form conjugate (PMB-vertepoffin) with hydrophobic domain in the PMB aggregate. The PMB-verteporfin was injected at dorsum manus of BALB/c nude mice. The concentrations of verteporfin in tissues were determined by measuring the fluorescence emitted at 700 nm (with excitation at 430 nm). To develop a murine SLN metastasis model, 5 x 105 human epidermoid carcinoma A431 cells with stable expression of GFP were injected to the forearm of BALB/c nude mice. Seven days after inoculation of cancer cells, 20 μL of PMB-verteporfin was injected at dorsum manus of BALB/c nude mice and 75 J of light energy was delivered using a 640 nm diode laser for a total treatment time of 1 min. Fifty-three mice were randomly assigned to the combination of PMB-verteporfin injection and light exposure (A), light exposure alone (B), PMB-verteporfin injection alone (C), and no treatment (D) groups. Ten days after PDT, brachial lymph nodes, which were considered as SLNs were harvested and evaluated by stereoscopic fluorescence microscope. And, DNA was extracted from harvested lymph node. Human Alu family sequence was detected by 7300 Real Time PCR system (Applied Biosystems, Carlsbad CA USA) to estimate metastatic volume. Results: The concentration of verteporfin in SLN was siginificantly higher than other organs including lung, liver, kidney and brachial skin. The group A significantly reduced the SLN metastasis (13%) comparing with , group B (57%), group C (46%) and group D (52%). The Ct value in a PCR of the combination of group A (Ct=29.17) significantly reduced the SLN metastasis comparing with group B (Ct=22.45, p=0.018), group C (Ct=25.58, p=0.018) and group D (Ct=25.54, p=0.005). Conclusions: These data suggested that PDT using PMB as a nanotransporter of verteporfin could be a minimally invasive treatment of SLN metastasis in breast cancer, and represent a potential alternative procedure to SLNB. Citation Format: Shimada K, Matsuda S, Jinno H, Konno T, Ito A, Arai T, Ishihara K, Kitagawa Y. The non-invasive treatment for sentinel lymph node metastasis by photodynamic therapy using a verteporfin solubilized phospholipid polymer aggregate [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-20.