68 Ga-DOTA.SA.FAPi as a Versatile Diagnostic Probe for Various Epithelial Malignancies: A Head-to-Head Comparison with 18 F-FDG.

Rationale and Objectives: Fibroblast Activation Protein (FAP) expressing cancer-associated fibroblasts has been a major breakthrough causing a paradigm shift in targeted theranostics focusing on the tumor microenvironment. In this study, a squaric acid derivative DOTA.SA.FAPi (SA.FAPi) has been evaluated as a potential diagnostic probe in diverse epithelial cancers and compared to the standard-of-care ¹⁸ F-FDG.
Methods: 25 patients enrolled in this prospective study underwent ¹⁸ F-FDG and ⁶⁸ Ga-SA.FAPi PET scans on two different days. For biodistribution, standardized uptake values (SUV) were computed by delineating region-of-interest on various body organs. For comparative analysis in disease identification, lesion tracer uptake was quantified using SUVs corrected for lean body mass (SUL), SUV _max , tumor-to-background ratio (TBR) with liver and blood pool as the reference, total lesion glycolysis (TLG for ¹⁸ F-FDG) and total lesion FAP expression (TLF for ⁶⁸ Ga-SA.FAPi).
Results: 25 patients (mean age: 58 ± 8 years) with four types of cancers including hepatocellular carcinoma (HCC, 56% of cohort), gall bladder carcinoma (GB Ca, 12%), adrenocortical carcinoma (ACC, 16%), and breast carcinoma (breast Ca, 16%) were prospectively evaluated. Physiological tracer uptake of ⁶⁸ Ga-SA.FAPi was noted in the salivary glands, thyroid, liver, pancreas, muscles and kidneys with variable uptake in the lacrimal glands, extra-ocular muscles, oral mucosa and uterus. Lesion-based comparative analysis between both the radiotracers demonstrated complete concordant findings in detection of all primary lesions and distant metastases in liver, bones, adrenals and peritoneum whereas discordant findings were noted in lung nodules (20%) and lymph nodes (13%). In overall analysis, ⁶⁸ Ga-SA.FAPi exhibited significantly higher SUV _max (10.3 vs 8.8, p-0.019), SUL _peak (6.8 vs 4.9, p-0.000) and SUL _avg (5.4 vs 4.1, p-0.019) in comparison to ¹⁸ F-FDG whereas TBR was comparable for both the tracers [TBR _Liver : median 1.9 (IQR: 2.6-1.4) vs 1.8 (2.6-1.1), p-0.275; TBR _Bloodpool : 2.1 (3.7-1.4) vs 2.0 (2.7-1.4), p-0.207]. In subcategorical analysis, ⁶⁸ Ga-SA.FAPi demonstrated higher SUV _max , SUL _peak and SUL _avg values for primary disease (SUV _max : 14.8 (18.7-9.7) vs (12.9-6.6), p-0.087; SUL _peak : 8.2 (11.2-6.8) vs 6.3 (8.5-4.4), p-0.037; SUL _avg : 6.9 ± 2.5 vs 5.1 ± 2.2, p-0.023] and distant metastases (8.8 vs 7.2, p-0.038); 6.3 (8.8-4.4) vs 3.6 (4.4-2.0), p-0.000; 5.4 vs 3.5, p-0.000] whereas comparable values were noted for both the tracers in nodal metastases [9 (13.5-4.1) vs 8 (12.7-4.7), p-0.726; 4.5 (6.2-1.8) vs 4.3 (5.7-2.2), p-0.727; 4.1 ± 2.3 vs 3.7 ± 1.8, p-0.129]. In primary disease, highest ⁶⁸ Ga-SA.FAPi avidity was noted in ACC followed by GB Ca and HCC. In distant metastases, gall bladder, lung and skeletal lesions demonstrated higher ⁶⁸ Ga-SA.FAPi avidity. Moreover, ⁶⁸ Ga-SA.FAPi identified five additional lung lesions which were missed by ¹⁸ F-FDG in one case of ACC.
Conclusion: ⁶⁸ Ga-SA.FAPi emerged as an effective, versatile diagnostic probe for imaging various epithelial malignancies similar to ¹⁸ F-FDG.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Jaya Shukla reports financial support was provided by Post Graduate Institute of Medical Education and Research.
(Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)