FAPI radiopharmaceuticals in nuclear oncology and theranostics of solid tumours: are we nearer to surrounding the hallmarks of cancer?

Abstract

[¹⁸F]FDG PET/CT is the most widely used PET radiopharmaceutical in oncology, but it is not exempt of diagnostic limitations. FAPI have emerged as a great tool in the management of several different solid tumours in which [¹⁸F]FDG is not able to provide enough information. The aim of this work was to evaluate the available evidence on diagnostic and therapeutic applications of PET/CT with FAPI radiopharmaceuticals. We underwent a non-systematic review focusing in the utility of FAPI radiopharmaceuticals in PET/CT diagnosis and in the treatment of several malignancies. FAPI radiopharmaceuticals present characteristics that can potentially overcome some known diagnostic limitations of [¹⁸F]FDG. FAPI radiopharmaceuticals present a high target-to-background ratio (TBR) in many solid tumours such as oesophageal cancer, gastric cancer, pancreatic cancer, hepatic cancer, colorectal cancer, breast cancer, ovarian, cervical cancer, and head and neck cancer. Available evidence suggests the high TBR improves sensitivity and specificity compared to [¹⁸F]FDG, especially for the detection of lymphadenopathies and peritoneal metastases, and may improve patient management and radiation treatment planning. Moreover, it is important to underline the potential theranostic application of FAPI radiopharmaceuticals.

Keywords: Cancer; FAPI; Nuclear oncology; PET/CT; Radiopharmaceutical therapy; Theranostic.

Fig. 1

Flow chart for study identification

Fig. 2

Sixty-seven year old male patient with newly diagnosed intrahepatic cholangiocarcinoma presenting a high tumour uptake on [⁶⁸Ga]Ga-FAPI-46 PET/CT (A and C) and a moderate tumour uptake on [¹⁸F]FDG PET/CT (B and D), with SUVmax 16.6 and 8.6 for [⁶⁸Ga]Ga-FAPI-46 and [¹⁸F]FDG, respectively. Maximum intensity projection (MIP) PET images (A and B) and transaxial PET/CT fusion images (C and D) are presented. Transaxial [⁶⁸Ga]Ga-FAPI-46 PET/CT fusion images (C) evidence the high [⁶⁸Ga]Ga-FAPI-46 uptake (white arrow) and the high TBR of the primary tumour with this radiopharmaceutical. In contrast, transaxial [¹⁸F]FDG PET/CT fusion images (D) show a comparatively higher background uptake and, therefore, a lower TBR, which negatively affects the delineation of the primary tumour

Fig. 3

Fifty-two year old female patient who presented a tumour in the right dorsal thigh that had been surgically resected, the pathology study labelling it as a solitary fibrous tumour corresponding to the primary tumour. Re-staging with [⁶⁸Ga]Ga-FAPI-46 PET/CT and [¹⁸F]FDG PET/CT was performed, detecting pulmonary metastases and diffuse osseous metastases with significantly increased uptake on [⁶⁸Ga]Ga-FAPI-46 PET/CT (A; white arrow, SUVmax 16.7) and low uptake on [¹⁸F]FDG PET/CT (B; white arrow, SUVmax 3.1)