Quantitative estimates of vascularity in solid tumors by non-invasive near-infrared spectroscopy.
We examined the relationship between non-invasive estimates of the tumor hemoglobin concentration by near-infrared spectroscopy (NIRS) and histological scores of tumor vascularity by Chalkley counts in seven tumor lines in nude mice [malignant gliomas: U87, U118, U373; small cell lung cancers (SCLC): 54A, 54B, DMS79; prostate cancer: MatLyLu (MLL)]. We also evaluated the effect of continuous anti-angiogenic treatment with TNP-470 on tumor hemoglobin concentration and tumor vascularity in U87 and MLL tumors. Non-invasive NIRS recordings were performed with a custom-built flash near-infrared spectrometer using light guide-coupled reflectance measurements at 800+/-10 nm. Chalkley counts were obtained from CD31-immunostained cryosections. The NIRS recordings in arbitrary absorbance units increased with tumor size in the individual tumors until a plateau was reached at approximately 150 mm(3). This plateau was relatively tumor line-specific. NIRS recordings at the plateau phase were strongly correlated (P<.001, n=71) to the histological vessel score (Chalkley count) of the same individual tumors excised immediately after the NIRS was performed. Non-invasive NIRS recordings of the highly vascularized gliomas (U87, U118, and U373) plus the MatLyLu tumor line were significantly higher than the three less vascularized SCLC tumor lines (P<.001). Continuous treatment with the anti-angiogenic compound TNP-470, an endothelial cell inhibitor, significantly retarded tumor growth in both U87 and MLL tumors, but all tumors eventually grew. When comparing treated and untreated tumors of similar size, both NIRS recordings and Chalkley counts were significantly lower in TNP-470-treated tumors (P<.05). In conclusion, the NIRS technique provides a non-invasive measure of the degree of vascularization in untreated tumors and the NIRS technique can measure modifications in tumor vascularization by anti-angiogenic therapy.
Kragh
M
M
Institute of Molecular Pathology, University of Copenhagen, 11 Frederik V Vej, Copenhagen DK-2100, Denmark.
Quistorff
B
B
Lund
E L
EL
Kristjansen
P E
PE
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D003510:Cyclohexanes; D004273:DNA, Neoplasm / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012717:Sesquiterpenes / Q000627:therapeutic use; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D004273:DNA, Neoplasm; D006454:Hemoglobins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol