Objective: To evaluate the hypoxia-avid agent 99mTc-HL91 (99mTc labeled 4, 9-diaza-3, 3, 10, 10-tetramethyldodecan-2, 11-dione dioxime) as the tracer of tumor "hot spot" imaging and the influence of tumor necrosis on the image.
Methods: After injection of 99mTc-HL91, 6 nude mice bearing human breast cancer MCF-7 and 18 nude mice bearing human pancreatic adenocarcinoma were subjected to gamma camera imaging, postmortem analysis, and autoradiography and imaging of tumor sections.
Results: The image of tumor was identified 1 hour after injection of 99mTc-HL91. Images demonstrated gradually increased 99mTc-HL91 uptake in the tumor 1-12 hours after injection (P < 0.05-0.001). Six hours after injection, the radioactivity ratios of tumor to thorax and tumor to head were higher than 2.1. Six hours after injection, the radioactivity ratios of tumor to brain, muscle, blood, heart, lung and kidney in pancreatic adenocarcinoma bearing nude mice were 101.0 +/- 114.7, 30.0 +/- 30.3, 19.9 +/- 21.9, 14.4 +/- 15.1, 3.71 +/- 2.41 and 0.46 +/- 0.26, respectively, and the radioactivity ratios in breast cancer MCF-7 bearing nude mice were close to these figures. The radioactivity of non-necrotic tumor was 3.77 times that of necrotic tumor. However, the radioactivity ratios of tumor to liver, intestine and stomach were lower than 1.3. Autoradiographs and images of tumor sections showed that the radioactivity was higher in the region of solid tumor than in the necrotic region.
Conclusion: 99mTc-HL91 via gamma camera positively identifies regional tumor in nude mice bearing human cancer. 99mTc-HL91 retention is lower in necrotic tumor than in non-necrotic tumor. The low radioactivity ratio of tumor to abdominal organs limits the application of 99mTc-HL91 in detecting abdominal tumors.