Correlation of apparent diffusion coefficient, FAP expression in IHC and [⁶⁸Ga]Ga‑FAPI‑46 uptake using integrated PET/MRI in high-grade soft tissue sarcoma: initial exploratory results

Fibroblast activation protein inhibitor (FAPI)-targeted positron emission tomography (PET) has emerged as a promising imaging approach in soft tissue sarcomas (STS), whereas magnetic resonance imaging (MRI) remains the diagnostic standard. We evaluated integrated [⁶⁸Ga]Ga‑FAPI‑46 PET/MRI including maximum standard uptake value (SUV_max), diffusion-weighted imaging, apparent diffusion coefficient (ADC), and contrast-enhanced sequences compared to FAP expression in immunohistochemistry for tumor assessment in high-grade STS.

Thirteen [⁶⁸Ga]Ga‑FAPI‑46 PET/MRI examinations from 9 patients were included, of which 4 were follow-up scans after therapy. All STS showed distinct FAPI uptake (median SUV_max 8.4; range 2.9-33). Mean SUV_max was 13 (2.9-33) for G2 and 8.4 (7.5-8.4) for G3 tumors. Neither SUV_max (P = 0.196) nor ADC (P = 0.895) differentiated between FNCLCC Grade 2 and Grade 3. A significant inverse correlation was observed between ADC_mean and SUV_max (Spearman's ρ = -0.70, 95% CI: -0.93 to - 0.07, P = 0.035). Immunohistochemistry demonstrated positive FAP expression in 4 of 9 patients, with significantly higher SUV_max in FAP-positive vs. negative tumors in immunohistochemistry (17.7 vs. 6.4; P = 0.047). High concordance of [⁶⁸Ga]Ga-FAPI-46 uptake and contrast enhancement was observed. Treatment responders showed marked reductions in SUV_max (40-70%) and increased ADC without significant changes in tumor size.

In this exploratory pilot study, [68Ga]Ga-FAPI-46 PET/MRI provided complementary functional information in high-grade STS. Although no correlation with grading was observed either using SUVmax or ADC, a significant inverse correlation between ADCmean and SUVmax was identified within this cohort. Preliminary observations regarding treatment monitoring suggested that early changes in tracer uptake and ADC may reflect treatment-related changes, however, these findings were derived from a small pilot cohort. Larger prospective studies are required to validate these observations and to further define the potential role of [68Ga]Ga-FAPI-46 PET/MRI in treatment monitoring and response assessment.