FAPI-74 PET/CT Using Either¹⁸F-AlF or Cold-Kit⁶⁸Ga Labeling: Biodistribution, Radiation Dosimetry, and Tumor Delineation in Lung Cancer Patients

Abstract

Ga-FAPI-2/4/46 have already been proposed as promising PET-tracers. However, the short half-life of 68 Ga (T1/2 68 min) creates problems with manufacture and delivery. 18 F (T1/2 110 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 18 F-AlF (Aluminum-Fluoride) and 68 Ga. Here we describe the in-vivo evaluation of 18 F-FAPI-74 and a proof-of-mechanism of 68 Ga-FAPI-74 labeled at ambient temperature. Methods: In ten patients with lung cancer PET-scans were acquired at 10 min, 1h and 3h after administration of 259±26 MBq 18 F-FAPI-74. Physiological biodistribution and tumor uptake were semi-quantitatively evaluated based on SUV at each time-point. Absorbed doses were evaluated using OLINDA/EXM 1.1 and QDOSE dosimetry software with the dose calculator IDAC-Dose 2.1. Identical methods were used to evaluate one exam after injection of 263 MBq 68 Ga-FAPI-74. Results: The highest contrast was achieved 1 h p.i. in primary tumors, lymph node and distant metastases with SUVmax >10, respectively. The effective dose per 100 MBq administered activity of 18 F-FAPI-74 was 1.4±0.2 mSv and for 68 Ga-FAPI-74 it was 1.6 mSv. Thus, the radiation burden of a diagnostic 18 F-FAPI-74 PET-scan is even lower than that of PET-scans with 18 F-FDG and other 18 F-tracers; 68 Ga-FAPI-74 is comparable to other 68 Ga-ligands. FAPI-PET/CT supported target volume definition for guiding radiotherapy. Conclusion: High contrast and low radiation burden of FAPI-74 PET/CT favors multiple clinical applications. Centralized large-scale production of 18 F-FAPI-74 or decentralized cold-kit labeling of 68 Ga-FAPI-74 allows flexible routine use.

Clinical Results of Fibroblast Activation Protein (FAP) Specific PET and Implications for Radiotherapy Planning: Systematic Review

“…Other publications report the propensity of FAP-specific PET to detect more NSCLC metastases than FDG PET, but patient collectives were too small to analyze whether this translates to more accurate staging. Figure 2) [24]. Applying a 3-fold threshold compared to healthy-appearing normal tissue resulted in volumes equal to those created by CT-based contouring (69.8 mL with FAP-specific PET vs. 67.4 mL with CT).…”

“…Giesel & Adeberg et al used a newer compound, FAPI-74, for target volume delineation in 10 patients with non-small-cell lung cancer (NSCLC, 8 adenocarcinomas, 2 squamous cell carcinomas, Figure 2) [24]. Applying a 3-fold threshold compared to healthy-appearing normal tissue resulted in volumes equal to those created by CT-based contouring (69.8 mL with FAP-specific PET vs. 67.4 mL with CT).…”

“…This research was originally published in JNM. Giesel, Adeberg et al[24] FAPI-74 PET/CT using either 18F-AlF or cold-kit 68Ga-labeling: Biodistribution, Radiation Dosimetry and Tumor Delineation in Lung Cancer Patients. J Nucl Med.…”

Fully-automated production of [68Ga]Ga-FAPI-46 for clinical application

“…with gallium-68 and fluor-18, resulting in [ 68 Ga]Ga-FAPI-74 and [ 18 F]F-FAPI-74, respectively (Giesel et al 2020).…”

Cancer-Associated Fibroblasts as Players in Cancer Development and Progression and Their Role in Targeted Radionuclide Imaging and Therapy

“…Toms et al [ 102 ] synthesized an 18 F-labelled FAPI ([ 18 F]FGlc-FAPI) and concluded from a preclinical study it is an interesting candidate for translation to the clinic, taking advantage of the longer half-life and physical imaging properties of 18 F. Giesel et al [ 113 ] describe the NOTA-chelator ligand FAPI-74 that can be labeled with both Al [ 18 F]F and 68 Ga. In ten patients with lung cancer PET-scans were acquired after administration of [ 18 F]F-FAPI-74, with the highest contrast achieved 1 h p.i.…”