Vascularity and uptake of photosensitizer in small human tumor nodules: Implications for intraperitoneal photodynamic therapy

Purpose: i.p. spread of cancers is a common clinical problem, with limited treatment options leading to morbidity and death. i.p. photodynamic therapy (IP-PDT) combines maximal surgical debulking of gross tumor with intraoperative light delivery to the peritoneum after preoperative i.v. injection of photosensitizer to treat residual disease. An issue of concern in IP-PDT is the potential lack of photosensitizer uptake by residual small tumor nodules (STNs) ≤5 mm in maximum diameter and by microscopic residual disease caused by incomplete development of a vascular supply. This study examined the existence of vasculature and Photofrin (PF) uptake in STNs in 12 patients in a Phase II clinical trial for IP-PDT. Experimental Design : Patients received PF 2.5 mg/kg i.v. 48 h before surgery. STNs obtained during surgery were cryosectioned, immunostained for platelet/endothelial cell adhesion molecule 1, and analyzed by light microscopy. Mean vascular densities in STNs were determined by counting microvessels within a ×200 field (0.28 mm 2 area). Sections were also examined for PF uptake by fluorescence image analysis using an epifluorescence microscope and IPLab Spectrum software. Results: Data obtained showed that tumors as small as 1 mm in diameter stained positive for platelet/endothelial cell adhesion molecule 1 and contained PF. A negative control from a patient not given PF showed no detectable fluorescence. The average of all mean vascular densities in STNs was determined to be 100 ± 29. Conclusions: We conclude that STNs, as small as 1 mm in diameter, have a functional vasculature, because these tumors show PF uptake after i.v. delivery. Both properties are crucial for the treatment of residual STNs by IP-PDT after surgical debulking.