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

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 ¹⁸F-FDG.

25 patients enrolled in this prospective study underwent ¹⁸F-FDG and ⁶⁸Ga-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 ¹⁸F-FDG) and total lesion FAP expression (TLF for ⁶⁸Ga-SA.FAPi).

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 ⁶⁸Ga-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, ⁶⁸Ga-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 ¹⁸F-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, ⁶⁸Ga-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 ⁶⁸Ga-SA.FAPi avidity was noted in ACC followed by GB Ca and HCC. In distant metastases, gall bladder, lung and skeletal lesions demonstrated higher ⁶⁸Ga-SA.FAPi avidity. Moreover, ⁶⁸Ga-SA.FAPi identified five additional lung lesions which were missed by ¹⁸F-FDG in one case of ACC.

⁶⁸Ga-SA.FAPi emerged as an effective, versatile diagnostic probe for imaging various epithelial malignancies similar to ¹⁸F-FDG.