RESUMO
In renal cell carcinoma (RCC), accurate imaging methods are required for treatment planning and response assessment to therapy. In addition, there is an urgent need for new therapeutic options, especially in metastatic RCC. One way to combine diagnostics and therapy in a so-called theranostic approach is the use of radioligands directed against surface antigens. For instance, radioligands against prostate-specific membrane antigen (PSMA) have already been successfully used for diagnosis and radionuclide therapy of metastatic prostate cancer. Recent studies have demonstrated that PSMA is expressed not only in prostate cancer but also in the neovasculature of several solid tumors, which has raised hopes to use PSMA-guided theranostic approaches in other tumor entities, too. However, data on PSMA expression in different histopathological subtypes of RCC are sparse. Because a better understanding of PSMA expression in RCC is critical to assess which patients would benefit most from theranostic approaches using PSMA-targeted ligands, we investigated the expression pattern of PSMA in different subtypes of RCC on protein level. Immunohistochemical staining for PSMA was performed on formalin-fixed, paraffin-embedded archival material of major different histological subtypes of RCC (clear cell RCC (ccRCC)), papillary RCC (pRCC) and chromophobe RCC (cpRCC). The extent and intensity of PSMA staining were scored semi-quantitatively and correlated with the histological RCC subtypes. Group comparisons were calculated with the Kruskal-Wallis test. In all cases, immunoreactivity was detected only in the tumor-associated vessels and not in tumor cells. Staining intensity was the strongest in ccRCC, followed by cpRCC and pRCC. ccRCC showed the most diffuse staining pattern, followed by cpRCC and pRCC. Our results provide a rationale for PSMA-targeted theranostic approaches in ccRCC and cpRCC.
RESUMO
BACKGROUND: [68Ga]Ga-FAPI-46 is a novel positron emission tomography (PET) ligand that targets fibroblast activation protein (FAP) expression as FAP inhibitor (FAPI) and could already show promising results in several tumor entities. It could be demonstrated that an increased FAP expression correlates with tumor aggressivity in urothelial carcinoma (UC). Given the limited value of [18F]FDG in UC, [68Ga]Ga-FAPI-46 could add diagnostic information in staging and response assessment in UC. We present the first data of [68Ga]Ga-FAPI-46 PET imaging in a pilot cohort of UC patients evaluating uptake characteristics in metastases and primary tumors. METHODS: Fifteen patients with UC prior to or after local treatment underwent [68Ga]Ga-FAPI-46 PET/CT imaging for detection of metastatic spread. We compared the biodistribution in non-affected organs and tumor uptake of UC lesions by standard uptake value measurements (SUVmean and SUVmax). Additionally, metastatic sites on PET were compared to its morphological correlate on contrast-enhanced computed tomography (CT). RESULTS: Overall, 64 tumor sites were detected on PET and/or CT. The highest uptake intensity was noted at the primary site (SUVmax 20.8 (range, 8.1-27.8)) followed by lymph node metastases (SUVmax 10.6 (range, 4.7-29.1)). In 4/15 (26.7%) patients there were [68Ga]Ga-FAPI-46-positive lesions that were missed on standard routine CT imaging. On the other hand, 2/15 patients had suspicious prominent bipulmonary nodules as well as pelvic lymph nodes previously rated as suspicious for metastatic spread on CT, but without increased FAPI expression; here histopathology excluded malignancy. CONCLUSION: [68Ga]Ga-FAPI-46 PET shows distinctly elevated uptake in UC lesions. Therefore, the tracer has potential as a promising new biomarker in metastatic UC patients, as [68Ga]Ga-FAPI-46 PET might improve detection of metastatic sites compared to CT alone. These findings highly emphasize larger studies investigating FAPI imaging in UC patients.
