Hypoxia imaging: four biomarkers go head to head
Four up-and-coming radiotracers to target areas of under-oxygenation, which indicates dying tissues and possible tumor proliferation, were compared and found to have similar biodistribution and uptake, according to a study published Feb. 3 in the Journal of Nuclear Medicine.
Researchers including Sean D. Carlin, PhD, from the department of radiochemistry and imaging sciences service at Memorial Sloan-Kettering Cancer Center in New York City, evaluated and Cu-64 diacetyl-bis(N4-methylsemicarbazone) (ATSM), F-18 fluoromisonidazole (FMISO), F-18 flortanidazole (HX4) and F-18 fluoroazomycin arabinoside (FAZA) using preclinical PET imaging systems and validated PET imaging with fluorescence immunohistochemistry and autoradiography. PET with one of the four tracers was performed on nine mice models. While Cu-64 ATSM showed the most tumor uptake using PET, further investigation showed that the tracer may not be ideal for hypoxia imaging and in fact showed an inverse uptake pattern when compared to the fluorine-based agents.
“Cu-64 ATSM showed the highest tumor accumulation and little renal clearance,” wrote Carlin et al. “However, the lack of correlation between Cu-64 ATSM distribution and immunohistochemistry hypoxia markers casts some doubt on the hypoxia selectivity of Cu-64 ATSM.”
Hypoxia PET imaging was compared with digital radiographs “pixel by pixel” as well as immunohistochemistry stains. All of the fluorine-based biomarkers revealed higher uptake in the presence of pimonidazole and in areas of CA staining. Maximum standardized uptake values were gauged at about 0.65 for HX4, 0.76 for FMISO and 0.41 for FAZA. For Cu-64 ATSM, it was 1.26. The jury is still out regarding which of the four will be best used to pinpoint areas of strangled tissues.
“Variations in tumor standardized uptake value and normal tissue distribution may determine the most appropriate clinical setting for each tracer,” wrote the authors.
Further study is required to determine best practices when choosing a biomarker for hypoxia PET imaging.