Microvascular permeability of albumin, vascular surface area, and vascular volume measured in human adenocarcinoma LS174T using dorsal chamber in SCID mice.
A novel method was developed to measure the effective permeability of microvessels in three-dimensional tumors. Two unique features characterized our approach: (i) Texas Red (with peak excitation and peak emission wavelengths of 596 and 615 nm, respectively) was used for macromolecular labeling, to minimize the absorption of fluorescence light by hemoglobin in blood. Thus the tumor tissue could be treated approximately as a uniform medium with respect to light absorption. (ii) The light absorption and scattering in tumor tissues were accounted for in relating the fluorescence intensity to the amount of Texas Red-labeled macromolecules extravasated. The vascular permeability of Texas Red-labeled bovine serum albumin in human tumor xenograft LS174T implanted in dorsal skin-fold chamber in severe combined immunodeficient mice was measured using this method. The average permeability-surface area product per unit volume (PS/V, x 10(-4) sec-1) and the average effective permeability (P, x 10(-7) cm/sec) were found to be 1.26 +/- 0.72 and 6.06 +/- 4.30, respectively; the fractional volume of tumor vessels (Vves/V, %) was found to be 9.2 +/- 2.9, and the total surface area of vessels per unit volume (S/V, cm2/cm3) was found to be 239 +/- 82. The errors in the estimation of these parameters are discussed. The method described here is general and can be adapted to study the microvascular permeability of superficial tumors in various organs in patients or animals.
Yuan
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Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Leunig
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Berk
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Jain
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RK
D000230:Adenocarcinoma / Q000098:blood supply* / Q000378:metabolism; D000818:Animals; D002199:Capillary Permeability; D003110:Colonic Neoplasms / Q000098:blood supply; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D051379:Mice; D016513:Mice, SCID; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D009391:Nephelometry and Turbidimetry; D019736:Prostheses and Implants; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*; D012867:Skin / Q000098:blood supply; D013047:Specific Pathogen-Free Organisms; D014183:Transplantation, Heterologous; D014743:Videotape Recording; D014966:Xanthenes / Q000493:pharmacokinetics
D005456:Fluorescent Dyes; D014966:Xanthenes; D012710:Serum Albumin, Bovine; C034657:Texas red