Comparison of 68Ga-FAPI and 18F-FDG PET/CT in metastases of papillary thyroid carcinoma

The recent development of quinoline-based PET tracers that act as fibroblast-activation-protein inhibitors (FAPIs) demonstrated promising preclinical and clinical results. FAP is overexpressed by cancer-associated fibroblasts of several tumor entities. Here, we quantify the tumor uptake on 68Ga-FAPI PET/CT of various primary and metastatic tumors to identify the most promising indications for future application. Methods:68Ga-FAPI PET/CT scans were requested by various referring physicians according to individual clinical indications that were considered insufficiently covered by 18F-FDG PET/CT or other imaging modalities. All PET/CT was performed 1 h after injection of 122-312 MBq of 68Ga-FAPI-04. We retrospectively identified 80 patients with histopathologically proven primary tumors or metastases or radiologically unequivocal metastatic lesions of histologically proven primary tumors. Tumor uptake was quantified by SUVmax and SUVmean (60% isocontour). Results: Eighty patients with 28 different tumor entities (54 primary tumors and 229 metastases) were evaluated. The highest average SUVmax (>12) was found in sarcoma, esophageal, breast, cholangiocarcinoma, and lung cancer. The lowest 68Ga-FAPI uptake (average SUVmax < 6) was observed in pheochromocytoma, renal cell, differentiated thyroid, adenoid cystic, and gastric cancer. The average SUVmax of hepatocellular, colorectal, head-neck, ovarian, pancreatic, and prostate cancer was intermediate (SUV 6-12). SUV varied across and within all tumor entities. Because of low background in muscle and blood pool (SUVmax < 2), the tumor-to-background contrast ratios were more than 3-fold in the intermediate and more than 6-fold in the high-intensity uptake group. Conclusion: Several highly prevalent cancers presented with remarkably high uptake and image contrast on 68Ga-FAPI PET/CT. The high and rather selective tumor uptake may open up new applications for noninvasive tumor characterization, staging examinations, or radioligand therapy.

We evaluated the potential usefulness of [68Ga]Ga-DOTA-FAPI-04 positron emission tomography/computed tomography (PET/CT) for the diagnosis of primary and metastatic lesions in various types of cancer, compared with [18F] FDG PET/CT.

For over 40 years, 18F-FDG has been the dominant PET tracer in neurology, cardiology, inflammatory diseases, and, most particularly, oncology. Combined with the ability to perform whole-body scanning, 18F-FDG has revolutionized the evaluation of cancer and has stifled the adoption of other tracers, except in situations where low avidity or high background activity limits diagnostic performance. The strength of 18F-FDG has generally been its ability to detect disease in the absence of structural abnormality, thereby enhancing diagnostic sensitivity, but its simultaneous weakness has been a lack of specificity due to diverse pathologies with enhanced glycolysis. Radiotracers that leverage other hallmarks of cancer or specific cell-surface targets are gradually finding a niche in the diagnostic armamentarium. However, none have had sufficient sensitivity to realistically compete with 18F-FDG for evaluation of the broad spectrum of malignancies. Perhaps, this situation is about to change with development of a class of tracers targeting fibroblast activation protein that have low uptake in almost all normal tissues but high uptake in most cancer types. In this review, the development and exciting preliminary clinical data relating to various fibroblast activation protein-specific small-molecule inhibitor tracers in oncology will be discussed along with potential nononcologic applications.