Hypoxia and Perfusion Measurements in Human Tumors—Initial Experience with Pimonidazole and IUdR

• Published in: Acta oncologica 2001, Vol.40 (8), p.924-928
• Main Authors: BEGG, Adrian C, JANSSEN, Hilde, SCIOT, Raf, HAUSTERMANS, Karin M. G, SPRONG, Debbie, HOFLAND, Ingrid, BLOMMESTIJN, Gerard, RALEIGH, James A, VARIA, Mahesh, BALM, Alfons, VAN VELTHUYZEN, Loes, DELAERE, Pierre
• Format: Article
• Language: English
• Subjects: Antibodies; Biological and medical sciences; Biopsy; Blood vessels; Diffusion; Esophageal Neoplasms - blood supply; Esophageal Neoplasms - physiopathology; Female; Head and Neck Neoplasms - blood supply; Head and Neck Neoplasms - physiopathology; Host-tumor relations. Immunology. Biological markers; Humans; Hypoxia - physiopathology; Idoxuridine - administration & dosage; Idoxuridine - pharmacokinetics; Image analysis; Kinetics; Male; Medical imaging; Medical sciences; Nitroimidazoles - administration & dosage; Nitroimidazoles - pharmacokinetics; Nucleic Acid Synthesis Inhibitors - administration & dosage; Nucleic Acid Synthesis Inhibitors - pharmacokinetics; Parameter estimation; Radiation-Sensitizing Agents - administration & dosage; Radiation-Sensitizing Agents - pharmacokinetics; Radiotherapy; Rectal Neoplasms - blood supply; Rectal Neoplasms - physiopathology; Regional Blood Flow; Specimen Handling; Surgery; Tumors; Uterine Cervical Neoplasms - blood supply; Uterine Cervical Neoplasms - physiopathology
• ISSN: 0284-186X; 1651-226X
• DOI: 10.1080/02841860152708198

We describe our preliminary studies on the development of methods to measure hypoxia in standard paraffin sections of human tumors. Three parameters were investigated. First, image analysis of tumor vascularity yielded the parameter diffusion limited fraction (DLF), which is the amount of tumor tissue greater than a fixed distance from the nearest blood vessel. Secondly, the amount of tumor tissue stained with antibodies against bound reduced products of the bioreductive marker pimonidazole was assessed. Finally, the fraction of blood vessels showing no surrounding tumor tissue labeled with IUdR, a cell kinetic marker, was measured. DLF and pimonidazole monitor primarily chronic hypoxia, while it is hypothesized that the IUdR-negative fraction monitors acute hypoxia. Feasibility was demonstrated in a series of 10 esophageal and 10 rectal tumors (no drug administration), 10 cervix tumors (pimonidazole) and 14 head and neck tumors (pimonidazole and IUdR). Significant differences between tumors were found for all parameters. DLF correlated significantly with the pimonidazole fraction when all images of all tumors were included, although mean values per tumor showed no correlation. The IUdR-negative fraction did not correlate with either of the other two parameters. We conclude that it is feasible to measure hypoxia-related, and possibly perfusion-related, parameters on paraffin sections for predictive purposes, although each method needs further validation. Each parameter will be correlated with outcome in a larger study on head and neck tumors treated with surgery with or without postoperative radiotherapy.