Quantitative Estimates of Vascularity in Solid Tumors by Non-Invasive Near-Infrared Spectroscopy

Abstract

We examined the relationship between non-invasive estimates of the tumor hemoglobin concentration by near-infrared spectroscopy (NIBS) 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, 5413, DMS79; prostate cancer: MatLyLu (MILL) ]. We also evaluated the effect of continuous anti-angiogenic treatment with TNP-470 on tumor hemoglobin concentration and tumor vascularity in U87 and MILL tumors. Non-invasive LAIRS recordings were performed with a custom-built flash near-infrared spectrometer using light guidecoupled reflectance measurements at 800±10 nm. Chalkley counts were obtained from CD31-immunostained cryosections. The LAIRS recordings in arbitrary absorbance units increased with tumor size in the individual tumors until a plateau was reached at approximately 150 mm3. This plateau was relatively tumor line-specific. LAIRS 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 LAIRS was performed. Non-invasive LAIRS 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 MILL tumors, but all tumors eventually grew. When comparing treated and untreated tumors of similar size, both LAIRS recordings and Chalkley counts were significantly lower in TNP-470-treated tumors (P<.05). In conclusion, the LAIRS technique provides a non-invasive measure of the degree of vascularization in untreated tumors and the LAIRS technique can measure modifications in tumor vascularization by anti-angiogenic therapy.

Keywords

• LAIRS
• Chalkley counts
• tumor angiogenesis
• TNP-470
• nude mice