A preliminary trial involving 22 glioblastoma patients at the University of Washington confirmed suspicions about the diminished success of radiotherapy when hypoxia permeates a glioblastoma tumor. Tissue was defined as hypoxic when the tumor-to-blood ratio of FMISO uptake was more than 1.2. The study, published in the May 2008 issue of Clinical Cancer Research, found that the presence of hypoxia before radiotherapy was associated with shorter tumor time to progression and patient survival.

ACRIN 6682 is a phase II trial of Cu-64 ATSM-PET/CT assessment of tumor hypoxia in cervical cancer. Dehdashti is the principal investigator. The prospective multicenter trial will assess the relationship between Cu-64 ATSM uptake in the primary cervical tumor and progression-free survival after chemoradiotherapy. One hundred women with invasive squamous cell cervical cancer who are scheduled to undergo radiation therapy and concurrent cisplatin chemotherapy will be examined.

Dehdashti published results of a preliminary study describing experience with 38 patients in 2008 (JNM 2008;49:210). Pretherapy Cu-60 ATSM-PET was performed, measuring tumor-to-muscle ratio before radiotherapy with chemotherapy follow-up in some cases. The response to therapy was followed for up to 79 months.

Hypoxia, measured with ATSM, had a dramatic effect on patient survival. More than 70% of patients with normoxic tumors, having an ATSM tumor-to-muscle ratio of less than 3.5, experienced progression-free survival in the 48 months after therapy. In contrast, only 30% of patients harboring hypoxic tumors, with a T/M ratio of more than 3.5, had not seen their cancers progress in the four-year period.

Cu-60 ATSM-PET has also shown promise in predicting the response and survival of patients undergoing neoadjuvant chemoradiation for advanced renal cancer. A pilot study, led by Dr. David Dietz at The Cleveland Clinic, suggests that ATSM-PET may be able to predict the response to neoadjuvant therapy before it is given. This could allow for tailoring treatment to the patient by perhaps directing likely nonresponders to clinical trials designed to increase the efficacy of standard rotational conformal radio-therapy, according to the authors.

Despite steady progress, both agents remain at a preliminary point in their development, according to Dr. Barry Siegel, chief of the nuclear medicine division at Mallinckrodt.

“We have a way to go, but we are on a path to having a hypoxia-imaging agent in clinical practice eventually,” he said.