68 Ga-DOTA-FAPI-04 PET/CT in the Detection of Thoracic SMARCA4-Deficient Undifferentiated Tumor.

ABSTRACT: Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a rare malignant disease. We present the case of a 56-year-old woman with thoracic SMARCA4-UT presenting as a mediastinal mass who underwent 68 Ga-DOTA-FAPI-04 PET/CT imaging. Intense 68 Ga-DOTA-FAPI-04 uptake was observed in the primary tumor and lymph node metastases. After 7 cycles of immune checkpoint inhibitor plus chemotherapy, the patient underwent mediastinal mass resection, and postoperative pathology confirmed a complete pathologic response. This case may provide valuable insights into the diagnosis and monitoring of the treatment response of thoracic SMARCA4-UT.

Superiority of [68Ga]Ga-DOTA-FAPI-04 PET/CT to [18F]FDG PET/CT in the evaluation of thymic epithelial tumours.

PURPOSE: The purpose of this study is to compare the ability of [68Ga]Ga-DOTA-FAPI-04 PET/CT and [18F]FDG PET/CT to stratify the malignancy and invasiveness of thymic epithelial tumours (TETs). METHODS: From April 2021 to November 2022, participants with suspected TETs confirmed by histopathology or follow-up imaging were prospectively analysed. All participants underwent [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT within 1 week. Clinical characteristics, CT features, and metabolic parameters (maximum standardized uptake value [SUVmax] and tumour-to-mediastinum ratio [TMR]) of subjects with different pathological types and stages were compared. The diagnostic capacities of [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT were compared using receiver operating characteristic (ROC) curves and McNemar's test. RESULTS: Fifty-seven participants were included. [68Ga]Ga-DOTA-FAPI-04 PET/CT was superior to [18F]FDG PET/CT in differentiating thymomas from thymic carcinomas (TCs) (AUC: 0.99 vs. 0.90, P = 0.02). Logistic regression revealed that SUVmax-FAPI (P = 0.04) was a significant predictive factor for TCs. SUVmax-FAPI and TMR-FAPI showed an excellent ability to differentiate low-risk thymomas (types A, AB, and B1), high-risk thymomas (types B2 and B3), and TCs (both P < 0.001). In thymomas, only SUVmax-FAPI (P < 0.001), TMR-FAPI (P < 0.001), and nonsmooth edges (P = 0.02) were significantly higher in the advanced-stage (Masaoka-Koga [MK] stage III/IV) group than in the early-stage group (MK stage I/II). Compared with [18F]FDG PET/CT, [68Ga]Ga-DOTA-FAPI-04 PET/CT showed significantly higher specificity (67% [46 of 69] vs. 93% [64 of 69], P < 0.001) in the detection of lymph node metastases and higher sensitivity (49% [19 of 39] vs. 97% [38 of 39], P < 0.001) in evaluating distant metastases. Both SUVmax-FAPI and TMR-FAPI were correlated with FAP expression (both r = 0.843, P < 0.001). CONCLUSION: [68Ga]Ga-DOTA-FAPI-04 PET/CT was superior to [18F]FDG PET/CT in evaluating the World Health Organization (WHO) classification, MK staging, and metastatic status of TETs. TRIAL REGISTRATION: ChiCTR2000038080, registration date 2020-09-09, https://www.chictr.org.cn/com/25/showproj.aspx?proj=61192.

Noninvasive interrogation of CD8+ T cell effector function for monitoring early tumor responses to immunotherapy.

Accurately identifying patients who respond to immunotherapy remains clinically challenging. A noninvasive method that can longitudinally capture information about immune cell function and assist in the early assessment of tumor responses is highly desirable for precision immunotherapy. Here, we show that PET imaging using a granzyme B-targeted radiotracer named 68Ga-grazytracer, could noninvasively and effectively predict tumor responses to immune checkpoint inhibitors and adoptive T cell transfer therapy in multiple tumor models. 68Ga-grazytracer was designed and selected from several radiotracers based on non-aldehyde peptidomimetics, and exhibited excellent in vivo metabolic stability and favorable targeting efficiency to granzyme B secreted by effector CD8+ T cells during immune responses. 68Ga-grazytracer permitted more sensitive discrimination of responders and nonresponders than did 18F-fluorodeoxyglucose, distinguishing between tumor pseudoprogression and true progression upon immune checkpoint blockade therapy in mouse models with varying immunogenicity. In a preliminary clinical trial with 5 patients, no adverse events were observed after 68Ga-grazytracer injection, and clinical responses in cancer patients undergoing immunotherapy were favorably correlated with 68Ga-grazytracer PET results. These results highlight the potential of 68Ga-grazytracer PET to enhance the clinical effectiveness of granzyme B secretion-related immunotherapies by supporting early response assessment and precise patient stratification in a noninvasive and longitudinal manner.