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Bone metastasis is of common occurrence in renal cell carcinoma with poor prognosis, but no optimal treatment approach has been established for bone metastatic renal cell carcinoma. To explore the potential therapeutic targets for bone metastatic renal cell carcinoma, we profile single cell transcriptomes of 6 primary renal cell carcinoma and 9 bone metastatic renal cell carcinoma. We also include scRNA-seq data of early-stage renal cell carcinoma, late-stage renal cell carcinoma, normal kidneys and healthy bone marrow samples in the study to better understand the bone metastasis niche. The molecular properties and dynamic changes of major cell lineages in bone metastatic environment of renal cell carcinoma are characterized. Bone metastatic renal cell carcinoma is associated with multifaceted immune deficiency together with cancer-associated fibroblasts, specifically appearance of macrophages exhibiting malignant and pro-angiogenic features. We also reveal the dominance of immune inhibitory T cells in the bone metastatic renal cell carcinoma which can be partially restored by the treatment. Trajectory analysis showes that myeloid-derived suppressor cells are progenitors of macrophages in the bone metastatic renal cell carcinoma while monocytes are their progenitors in primary tumors and healthy bone marrows. Additionally, the infiltration of immune inhibitory CD47+ T cells is observed in bone metastatic tumors, which may be a result of reduced phagocytosis by SIRPA-expressing macrophages in the bone microenvironment. Together, our results provide a systematic view of various cell types in bone metastatic renal cell carcinoma and suggest avenues for therapeutic solutions. Single-cell profiling of primary and bone metastatic renal cell carcinoma suggests variation in intratumoral heterogeneity between samples and the is a valuable resource for examining the underlying pathogenic mechanisms for these cancers. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to compare the diagnostic value of gallium-68-labeled fibroblast activation protein inhibitor positron emission tomography/computed tomography ( 68 Ga-FAPI PET/CT) and fluorine-18-labeled fluorodeoxyglucose PET/CT ( 18 F-FDG PET/CT) for detecting recurrent colorectal cancers (CRCs)., Materials and Methods: Fifty-six patients (age: 18-80 years, 31 men and 25 women) with suspected recurrent CRC were enrolled and underwent 18 F-FDG PET/CT and 68 Ga-FAPI PET/CT sequentially within 1 week. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were estimated and compared between the two modalities by using Student's t -test. The Wilcoxon signed-rank test was used to compare peritoneal carcinoma index (PCI) scores between the two imaging modalities., Results: 68 Ga-FAPI PET/CT showed higher sensitivity for detecting recurrence (93 % vs. 79 %); lymph node metastasis (89 % vs. 78 %), particularly peritoneal lymph node metastasis (92 % vs. 63 %); and metastatic implantation on the intestinal wall (100 % vs. 25 %) compared to 18 F-FDG PET/CT. However, 68 Ga-FAPI PET/CT showed lower sensitivity for detecting bone metastasis (67 % vs. 100 %). The mean SUVmax values of peritoneal metastases and metastatic implantation on the intestinal wall were 4.28 ± 2.70 and 7.58 ± 1.66 for 18 F-FDG PET/CT and 5.66 ± 1.97 and 6.70 ± 0.25 for 68 Ga-FAPI PET/CT, respectively. Furthermore, 68 Ga-FAPI PET/CT showed significantly higher TBR for peritoneal metastatic lesions (4.22 ± 1.47 vs. 1.41 ± 0.89, p < 0.0001) and metastatic implantation on the intestinal wall (5.63 ± 1.24 vs. 2.20 ± 0.5, p = 0.02) compared to 18 F-FDG PET/CT. For the same patient, 68 Ga-FAPI PET/CT yielded a more accurate PCI score and a greater area under the curve value for the receiver operating characteristic curve (p < 0.01) than 18 F-FDG PET/CT., Conclusion: 68 Ga-FAPI PET/CT was superior to 18 F-FDG PET/CT for detecting recurrence and peritoneal metastases. Hence, we propose the combination of these two modalities for better clinical diagnosis and management of patients with CRC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: This study aimed to compare the diagnostic value of [ 68  Ga]Ga-DOTA-FAPI-04 and [ 18 F]FDG PET/CT imaging for primary lesions and metastatic lymph nodes in patients with tonsil cancer., Method: Twenty-one tonsil cancer patients who underwent [ 68  Ga]Ga-DOTA-FAPI-04 and [ 18 F]FDG PET/CT scans within two weeks in our centre were retrospectively enrolled. The maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR) of the two tracers were compared by using the Mann‒Whitney U test. In addition, the sensitivity, specificity, and accuracy of the two methods for diagnosing metastatic lymph nodes were analysed., Results: In detecting primary lesions, the efficiency was higher for [ 68  Ga]Ga-DOTA-FAPI-04 PET/CT (20/22) than for [ 18 F]FDG PET/CT (9/22). Although [ 68  Ga]Ga-DOTA-FAPI-04 uptake (SUVmax, 5.03 ± 4.06) was lower than [ 18 F]FDG uptake (SUVmax, 7.90 ± 4.84, P = 0.006), [ 68  Ga]Ga-DOTA-FAPI-04 improved the distinction between the primary tumor and contralateral normal tonsillar tissue. The TBR was significantly higher for [ 68  Ga]Ga-DOTA-FAPI-04 PET/CT (3.19 ± 2.06) than for [ 18 F]FDG PET/CT (1.89 ± 1.80) (p < 0.001). In lymph node analysis, SUVmax and TBR were not significantly different between [ 68  Ga]Ga-DOTA-FAPI-04 and [ 18 F]FDG PET/CT (7.67 ± 5.88 vs. 8.36 ± 6.15, P = 0.498 and 5.56 ± 4.02 vs. 4.26 ± 3.16, P = 0.123, respectively). The specificity and accuracy of [ 68  Ga]Ga-DOTA-FAPI-04 PET/CT were higher than those of [ 18 F]FDG PET/CT in diagnosing metastatic cervical lymph nodes (all P < 0.05)., Conclusion: The availability of [ 68  Ga]Ga-DOTA-FAPI-04 complements the diagnostic results of [ 18 F]FDG by improving the detection rate of primary lesions and the diagnostic accuracy of cervical metastatic lymph nodes in tonsil cancer compared to [ 18 F]FDG., (© 2024. The Author(s).)

The low detection rate of primary tumors by current diagnostic techniques remains a major concern for patients with head and neck cancer of unknown primary (HNCUP). Therefore, in this study, we aimed to investigate the potential role of 68 Ga-labeled fibroblast activation protein inhibitor ( 68 Ga-FAPI) PET/CT compared with 18 F-FDG PET/CT for the detection of primary tumors of HNCUP. Methods: In this prospective comparative imaging trial conducted at Fudan University Shanghai Cancer Center, 91 patients with negative or equivocal findings of a primary tumor by comprehensive clinical examination and conventional imaging were enrolled from June 2020 to September 2022. The presence of a primary tumor was recorded by 3 experienced nuclear medicine physicians. Primary lesions were validated by histopathologic analysis and a composite reference standard. Results: Of the 91 patients (18 women, 73 men; median age, 60 y; age range, 24-76 y), primary tumors were detected in 46 (51%) patients after a thorough diagnostic work-up. 68 Ga-FAPI PET/CT detected more primary lesions than 18 F-FDG PET/CT (46 vs. 17, P < 0.001) and showed better sensitivity, positive predictive value, and accuracy in locating primary tumors (51% vs. 25%, 98% vs. 43%, and 51% vs. 19%, respectively). Furthermore, 68 Ga-FAPI PET/CT led to treatment changes in 22 of 91 (24%) patients compared with 18 F-FDG PET/CT. The Kaplan-Meier curve illustrated that patients with unidentified primary tumors had a significantly worse prognosis than patients with identified primary tumors (hazard ratio, 5.77; 95% CI, 1.86-17.94; P = 0.0097). Conclusion: 68 Ga-FAPI PET/CT outperforms 18 F-FDG PET/CT in detecting primary lesions and could serve as a sensitive, reliable, and reproducible imaging modality for HNCUP patients., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Fibroblast activation protein (FAP), a type II integral membrane serine protease, is a promising target for tumor diagnosis and therapy. OncoFAP has been recently discovered for PET imaging procedures for various solid malignancies. In this study, we presented the development of manual radiolabeling procedures for the preparation of OncoFAP-based radiopharmaceuticals for cancer imaging. A novel series of [ 68 Ga/ 177 Lu]Ga/Lu-FAPI-FUSCC-I/II were produced with high radiochemical yields. [ 68 Ga]Ga-FAPI-FUSCC-I/II and [ 177 Lu]Lu-FAPI-FUSCC-I/II were stable in phosphate-buffered saline, fetal bovine serum, and human serum for at least 3 h. In vitro cellular uptake and blocking experiments implied that they had specificity to FAP. Additionally, the low nanomolar IC 50 values of FAPI-FUSCC-II indicated that it had a high target affinity to FAP. The in vivo biodistribution and blocking study in mice bearing HT-1080-FAP tumors showed that both exhibited specific tumor uptake. [ 68 Ga]Ga-FAPI-FUSCC-II showed a higher tumor uptake and a higher tumor/nontarget ratio than [ 68 Ga]Ga-FAPI-FUSCC-I and [ 68 Ga]Ga-FAPI-04. The results of ex vivo biodistribution were in accordance with the biodistribution results. Clinical [ 68 Ga]Ga-FAPI-FUSCC-II-PET/CT imaging further demonstrated its favorable biodistribution and kinetics with elevated and reliable uptake by primary tumors (maximum standardized uptake value (SUV max ), 12.17 ± 6.67) and distant metastases (SUV max , 9.24 ± 4.28). In summary, [ 68 Ga]Ga-FAPI-FUSCC-II displayed increased tumor uptake and retention compared to [ 68 Ga]Ga-FAPI-04, giving it potential as a promising tracer for the diagnostic imaging of malignant tumors with positive FAP expression.