68Ga-FAPI PET/CT: Biodistribution and Preliminary Dosimetry Estimate of 2 DOTA-Containing FAP-Targeting Agents in Patients with Various Cancers

Frederik L Giesel, Clemens Kratochwil, Thomas Lindner, Manfred M Marschalek, Anastasia Loktev, Wencke Lehnert, Jürgen Debus, Dirk Jäger, Paul Flechsig, Annette Altmann, Walter Mier, Uwe Haberkorn, Frederik L Giesel, Clemens Kratochwil, Thomas Lindner, Manfred M Marschalek, Anastasia Loktev, Wencke Lehnert, Jürgen Debus, Dirk Jäger, Paul Flechsig, Annette Altmann, Walter Mier, Uwe Haberkorn

Abstract

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 SUVmean and SUVmaxResults: 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 SUVmax, 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.

Keywords: PET/CT; biodistribution; cancer-associated fibroblasts; dosimetry; fibroblast activation protein; radiotracer tissue kinetics.

© 2019 by the Society of Nuclear Medicine and Molecular Imaging.

Figures

FIGURE 1.
FIGURE 1.
Molecular structure of 68Ga-FAPI-2 and 68Ga-FAPI-4.
FIGURE 2.
FIGURE 2.
68Ga-FAPI-2 and 68Ga-FAPI-4 at different imaging time points (10 min, 1 h, and 3 h after injection) in 2 patients with metastasized breast cancer. Rapid tumor targeting and fast blood clearance are followed by long plateau phase without relevant change in image contrast (top). In comparison to 68Ga-FAPI-2, 68Ga-FAPI-4 is characterized by prolonged tumor retention time (bottom). LW = lumbar body.
FIGURE 3.
FIGURE 3.
Intraindividual comparison of 6 patients with 6 different tumor entities undergoing 18F-FDG PET and 68Ga-FAPI PET imaging within less than 9 d. Five of 6 patients present similar strong tumor uptake with 18F-FDG and 68Ga-FAPI, and 3 of 6 could benefit from lower background in liver or pharyngeal mucosa. In contrast, iodine-negative thyroid cancer patient presented only minor 68Ga-FAPI tracer uptake compared with 18F-FDG. Ca = cancer; NSCLC = non–small cell lung cancer.
FIGURE 4.
FIGURE 4.
PET-based biodistribution analysis of 6 patients intraindividually comparing 18F-FDG PET and 68Ga-FAPI PET, imaged at 1 h after injection. GI = gastrointestinal.
FIGURE 5.
FIGURE 5.
Interindividual comparison of 25 patients examined with 68Ga-FAPI-2 and 25 patients examined with 68Ga-FAPI-4 PET at 1 h after injection. GI = gastrointestinal.

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