Vascularity and uptake of photosensitizer in small human tumor nodules: implications for intraperitoneal photodynamic therapy.
OBJECTIVE
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) < or =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.


METHODS
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 x200 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.
Menon
C
C
Harrison Department of Surgical Research, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
Kutney
S N
SN
Lehr
S C
SC
Hendren
S K
SK
Busch
T M
TM
Hahn
S M
SM
Fraker
D L
DL
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000032:analysis; D003131:Combined Modality Therapy; D017323:Dihematoporphyrin Ether / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D010778:Photochemotherapy / Q000009:adverse effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis
D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017323:Dihematoporphyrin Ether