Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts of several tumor entities. The recent development of quinoline-based PET tracers that act as FAP inhibitors (FAPIs) demonstrated promising results preclinically and already in a few clinical cases. Consequently, these tracers are now applied in our hospital to amend the diagnostics of cancer patients facing the limitations of standard examinations. Here, we analyze the tissue biodistribution and preliminary dosimetry of 2 members of this new class of PET radiopharmaceutical. Methods: A preliminary dosimetry estimate for ⁶⁸Ga-FAPI-2 and ⁶⁸Ga-FAPI-4 was based on 2 patients examined at 0.2, 1, and 3 h after tracer injection using the QDOSE dosimetry software suit. Further PET/CT scans of tumor patients were acquired 1 h after injection of either ⁶⁸Ga-FAPI-2 (n = 25) or ⁶⁸Ga-FAPI-4 (n = 25); for 6 patients an intraindividual related ¹⁸F-FDG scan (also acquired 1 h after injection) was available. For the normal tissue of 16 organs, a 2-cm spheric volume of interest was placed in the parenchyma; for tumor lesions, a threshold-segmented volume of interest was used to quantify SUV_mean and SUV_maxResults: Similar to literature values for ¹⁸F-FDG, ⁶⁸Ga-DOTATATE, and ⁶⁸Ga-PSMA-11, an examination with 200 MBq of ⁶⁸Ga-FAPI-2 or ⁶⁸Ga-FAPI-4 corresponds to an equivalent dose of approximately 3-4 mSv. After a fast clearance via the kidneys, the normal organs showed a low tracer uptake with only minimal changes between 10 min and 3 h after injection. In ⁶⁸Ga-FAPI-2, the tumor uptake from 1 to 3 h after injection decreased by 75%, whereas the tumor retention was prolonged with ⁶⁸Ga-FAPI-4 (25% washout). Regarding tumor-to-background ratios, at 1 h after injection both ⁶⁸Ga-FAPI tracers performed equally. In comparison to ¹⁸F-FDG, the tumor uptake was almost equal (average SUV_max, 7.41 for ¹⁸F-FDG and 7.37 for ⁶⁸Ga-FAPI-2; not statistically significant); the background uptake in brain (11.01 vs. 0.32), liver (2.77 vs. 1.69), and oral/pharyngeal mucosa (4.88 vs. 2.57) was significantly lower with ⁶⁸Ga-FAPI. Other organs did not relevantly differ between ¹⁸F-FDG and ⁶⁸Ga-FAPI. Conclusion: FAPI PET/CT is a new diagnostic method in imaging cancer patients. In contrast to ¹⁸F-FDG, no diet or fasting in preparation for the examination is necessary, and image acquisition can potentially be started a few minutes after tracer application. Tumor-to-background contrast ratios were equal to or even better than those of ¹⁸F-FDG.

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