Novel amino-acid PET tracer may increase specificity for certain cancers

A first-in-human study of (D)-18F-fluoromethyltyrosine (D-18F-FMT), a tyrosine derivative, is being evaluated for diagnostic imaging of non-small cell lung cancer (NSCLC) as well as head and neck squamous cell cancers (HNSCC). Results show that it could provide some differentiation in a space dominated by FDG, according to a study published Sept. 25 in the Journal of Nuclear Medicine.

Amino-acid imaging is being touted as an elevated technique compared to metabolic imaging with FDG-PET. While FDG has been used widely with great benefit for cancer imaging, it tends to underwhelm when it comes to specificity due to tracer uptake in non-cancerous tissues.

“Especially, the well-known accumulation of F-18 FDG in inflammatory lesions—indistinguishable from tumor accumulation—can lead to over-staging of patients,” wrote Irene A. Burger, MD, from the division of nuclear medicine and department of medical radiology at the University Hospital of Zurich, Switzerland, and colleagues. “One well-established concept for improved tumor specificity is the increased expression of amino acid transporters in transformed cancer cells, leading to increased accumulation of amino acids in tumor cells.”

However, the jury is still out regarding the sensitivity of FMT when compared to FDG. A total of 18 patients were included in the prospective, multi-site study. Of these subjects, 10 had biopsy-confirmed NSCLC and the remaining eight had HNSCC. All were scanned with FDG PET/CT within 21 days prior to undergoing FMT PET/CT imaging.

Results of the study compared the sensitivity and specificity of both FDG and FMT. Scanning with FDG PET/CT revealed 52 positive tumors, of which 42 were malignant. Of these 42 malignant tumors, 32 were caught by FMT PET/CT and 10 lesions showed no tracer uptake greater than the blood pool.

This means that FDG led to true-positives in 42 lesions, false positives in 10 lesions and two false negatives. In contrast, the use of FMT resulted in 34 true positives, 8 true negatives, 10 false negatives and two false positives. Overall, the accuracy of both techniques was gauged at 78 percent. Individual lesion-based detection rate for FDG was 95 percent, and for FMT, 77 percent.

With additional study, FMT PET/CT may have some predictive value over FDG, as spiked FMT tumor-to-blood ratio was associated with poor overall survival, whereas FDG had no such correlation. 

“The results showed a trend toward a lower sensitivity for D-18F-FMT than F-18 FDG along with a higher specificity due to the lack of uptake in inflammatory tissues,” the authors concluded. “This finding may lead to improved clinical management of patients in areas with endemic granulomatous disease.”

Additional studies in larger patient populations are needed to validate this research and make way for regulatory approval.