PET with 62Cu-ATSM, 62Cu-PTSM identifies hypoxia, perfusion in pulmonary lesions

Evaluating lung masses by visualizing hypoxia and perfusion is feasible with copper-diacetyl-bis (62Cu-ATSM) and copper-pyruvaldehyde-bis (62Cu-PTSM) PET scans, according to a study published in the November issue of the American Journal of Roentgenology.

Lung cancer has the highest cancer-related mortality and is the second most common malignancy in men and women in the U.S. Most solid tumors are commonly characterized by hypoxia, which prompts resistance to treatment, enhances tumor progression, and reduces patient survival. There is current difficulty in distinguishing malignancies from false-positives, and hypoxia may be used as a potential imaging target because it is one of the signatures of malignancy.

“Recently, novel molecular imaging techniques using 62Cu-ATSM have been used to image tissue hypoxia. These techniques take advantage of several positron-emitting copper isotopes, including 60Cu, 61Cu, 62Cu, and 64Cu, which vary in positron energy and half-life,” wrote Tian Zhang, MD, of the Duke University Medical Center in North Carolina. 62Cu-PTSM, on the other hand, is reduced by mitochondria and is retained in most issues, so it can be used as a marker of tissue perfusion.

Though PET has been studied with these radioisotopes already, examining tumor hypoxia concurrently with image tumor perfusion has not been previously done. Thus, Zhang and colleagues designed a study to explore the feasibility and utility of 62Cu-ATSM and 62Cu-PTSM PET in characterizing both tissue hypoxia and perfusion.

Ten patients from Duke University Medical Center were originally studied using 62Cu-ATSM and 62Cu-PTSM PET scans to characterize tumors based on perfusion and hypoxia. However, several limitations eventually whittled the study population down to six patients. Proteomic arrays looking at specific proangiogenic, survival, and proinflammatory targets were also assessed.

Results revealed that visualization of areas with hypoxia normalized for perfusion was possible. All examined tumors demonstrated some hypoxia. Even given the small sample size, a positive relationship was seen between epidermal growth factor levels and 62Cu-ATSM -detected hypoxia.  

“The 62Cu-ATSM-to-62Cu-PTSM ratio could possibly improve characterization of hypoxia, particularly in different areas of pulmonary lesions,” wrote the study’s authors. “Given the practical nature of PET in both cost and time efficiency when compared with MRI, we suggest that the 62Cu-ATSM and 62Cu-PTSM techniques provide a potentially clinically useful tool in imaging both tissue hypoxia and perfusion.”