FAPI-74 PET/CT Using Either 18F-AlF or Cold-Kit 68Ga Labeling: Biodistribution, Radiation Dosimetry, and Tumor Delineation in Lung Cancer Patients

Abstract

⁶⁸Ga-fibroblast activation protein inhibitors (FAPIs) 2, 4, and 46 have already been proposed as promising PET tracers. However, the short half-life of ⁶⁸Ga (68 min) creates problems with manufacture and delivery. ¹⁸F (half-life, 110 min) labeling would result in a more practical large-scale production, and a cold-kit formulation would improve the spontaneous availability. The NOTA chelator ligand FAPI-74 can be labeled with both ¹⁸F-AlF and ⁶⁸Ga. Here, we describe the in vivo evaluation of ¹⁸F-FAPI-74 and a proof of mechanism for ⁶⁸Ga-FAPI-74 labeled at ambient temperature. Methods: In 10 patients with lung cancer, PET scans were acquired at 10 min, 1 h, and 3 h after administration of 259 ± 26 MBq of ¹⁸F-FAPI-74. Physiologic biodistribution and tumor uptake were semiquantitatively evaluated on the basis of SUV at each time point. Absorbed doses were evaluated using OLINDA/EXM, version 1.1, and QDOSE dosimetry software with the dose calculator IDAC-Dose, version 2.1. Identical methods were used to evaluate one examination after injection of 263 MBq of ⁶⁸Ga-FAPI-74. Results: The highest contrast was achieved in primary tumors, lymph nodes, and distant metastases at 1 h after injection, with an SUV_max of more than 10. The effective dose per a 100-MBq administered activity of ¹⁸F-FAPI-74 was 1.4 ± 0.2 mSv, and for ⁶⁸Ga-FAPI-74 it was 1.6 mSv. Thus, the radiation burden of a diagnostic ¹⁸F-FAPI-74 PET scan is even lower than that of PET scans with ¹⁸F-FDG and other ¹⁸F tracers; ⁶⁸Ga-FAPI-74 is comparable to other ⁶⁸Ga ligands. FAPI PET/CT supported target volume definition for guiding radiotherapy. Conclusion: The high contrast and low radiation burden of FAPI-74 PET/CT favor multiple clinical applications. Centralized large-scale production of ¹⁸F-FAPI-74 or decentralized cold-kit labeling of ⁶⁸Ga-FAPI-74 allows flexible routine use.

Keywords: FAPI PET/CT; cancer-associated fibroblasts; cold kit; lung cancer; radiation dosimetry.

FIGURE 1.

Time-dependent biodistribution of ¹⁸F-FAPI-74 in normal organs and tumor.

FIGURE 2.

(A) Maximum-intensity projections of ¹⁸F-FAPI-74 PET at 10 min, 1 h, and 3 h after injection. (B) FAPI PET/CT presents favorable discrimination between tumor and myocardium. (C–E) Some FAPI-positive lesions were confirmed by CT correlate (C), whereas additional bone lesions were only detected per FAPI PET (D and E). All highlighted arrows represent FAPI uptake with morphological correlation. p.i. = after injection.

FIGURE 3.

(A) Maximum-intensity projections of ⁶⁸Ga-FAPI-74 PET at 10 min, 1 h, and 3 h after injection. (B–E) Direct comparison of contrast-enhanced CT (B), fusion imaging (C), and FAPI PET (D). (E and F) Superior tumor delineation consecutively improved dose application to tumor volume using volumetrically modulated arc therapy. Positive FAP uptake is marked by arrows (B–F). Green outline = GTV; orange outline = clinical target volume; red outline = planning target volume. p.i. = after injection.

FIGURE 4.

GTV automatically segmented per FAPI PET at different SUV thresholds (x = blood-pool–fold) in comparison to CT-based standard of reference.