Imaging is too often looked at as an afterthought rather than an integral part of clinical cancer trials, according to Michael M. Graham, MD, PhD, president of SNM, the molecular imaging society.
"Imaging has to be built in at the front end because it's relatively expensive," Dr. Graham told a roomful of radiation oncologists. "If you get a trial going, get the funding, and then go talk to your nuclear medicine person and ask for PET images, he's going to tell you that each image will cost around $1,500. They don't like to give those scans away. But if you ask from the start, you can build those costs into the budget."
And it would be a worthwhile expenditure, as metabolic imaging can truly advance the diagnosis, staging, and response assessment, said Dr. Graham, who is also the director of nuclear medicine and a professor of radiology at the University of Iowa in Iowa City.
At the 2010 ASTRO Multidisciplinary Head and Neck Cancers Symposium in Chandler, Ariz., Dr. Graham outlined the three areas where metabolic imaging is up and coming for head and neck cancers: metabolism, hypoxia, and receptors.
There are a number of molecular imaging agents that can be used to view metabolic pathways of cancer, with 18F-fluorodeoxyglucose (FDG) leading the pack. FDG measures glycolysis, and the radiotracer has proven itself many times over in head and neck cancer.
Dr. Graham cited a meta-analysis of FDG-PET and FDG-PET/CT in head and neck cancer, which found that the molecular modalities had an accuracy of 91% to 98% for the detection of lymph node metastases compared with CT (60% to 90% accuracy). In addition, PET imaging changed patient management in 30% to 57% of the cases (J Clin Oncol online, August 20, 2009).
Another glucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG), has interesting possibilities, Dr. Graham said. This fluorescent agent was recently used successfully as a topical agent in ex vivo tissue and could be useful for surgeons to pinpoint malignant tissue. "It's an example of imaging that is not necessarily nuclear or radioactive," he said (Int J Cancer 124:2634-2642, 2009).
Other metabolism-measuring agents that home in on tumor metabolism are 3'-deoxy-3'-[18F]-fluorothymidine (FLT), which measures DNA synthesis; 1-[11C]-acetate for lipid synthesis; and amino acids for protein synthesis.
11C -acetate "is a simple molecule that gets into a lot of metabolic pathways," Dr. Graham explained. "In tumors, it gets primarily into the lipid synthesis pathway and its uptake in tumors is a marker of lipid synthesis. It has turned out to be particularly useful in prostate cancer."
A study out of Umea University Hospital in Sweden used 11C-acetate PET imaging (ACE-PET) for staging head and neck cancer and found that it was as good as, if not better than, FDG at detecting lesions (Eur J Nucl Med Mol Imaging 34:651-657, 2007).
"But before you run out and ask your nuclear medicine people to start doing 11C-acetate imaging, you want to recognize that 11C-acetate has a half-life of 20 minutes. Also, it's made on a cyclotron and you have to have the synthesis equipment ready to go. It's not the simplest [agent to produce], but it may be an interesting approach," he said.
For DNA synthesis, FLT is a radiotracer to watch. Korean investigators used FLT-PET before and after treatment with gefitinib (Iressa) in patients with advanced adenocarcinoma of the lung. They reported that pretreatment standard uptake value (SUVmax) of the tumors did not differ between responders and nonresponders to treatment. At seven days after initiation of therapy, the percent changes in SUVmax were significantly different between the two groups (Clin Cancer Res 14:7423-7429, 2008).