[(68)Ga]Ga-PSMA-11 PET/CT has potential application in predicting tumor HIF-2α expression and therapeutic response to HIF-2α antagonists in patients with RCC.

To evaluate the efficacy of parameters derived from [68Ga]Ga-PSMA-11 PET/CT images in predicting pathological HIF-2α expression in primary tumors among patients with renal cell carcinoma (RCC). Fifty-three RCC patients with preoperative [68Ga]Ga-PSMA-11 PET/CT scans and complete surgical specimens were retrospectively enrolled in this study. Radiographic parameters were obtained from PET/CT images, and immunohistochemistry was used to measure the expression of HIF-2α and PSMA. Continuous variables and categorical variables were analyzed by the Mann-Whitney U test and chi-square test, respectively. ROC analysis was used to test the efficacy of several preoperative parameters in identifying pathological HIF-2α expression. Univariable logistic regression analyses were performed for significant parameters to predict pathological HIF-2α expression in RCC. Of the 53 tumors, 29 (54.7%) had high expression of HIF-2α. The SUVmax was significantly different in the HIF-2α expression subgroups (p < 0.001). SUVmax emerged as the most significant parameter to differentiate HIF-2α expression subgroups (high vs. low), with the AUC of 0.93 (95% CI 0.85-1.00, p < 0.001), sensitivity of 90%, and specificity of 88%. Furthermore, SUVmax was confirmed as the most significant predictor of HIF-2α expression level by univariable logistic regression model analysis (odds ratio 1.39, 95% CI 1.17-1.65, p < 0.001). Consistent with the radiographic results of [68Ga]Ga-PSMA-11 PET/CT, the staining intensity of pathological PSMA was significantly higher in HIF-2α-high-expressing tumors (p = 0.003). [68Ga]Ga-PSMA-11 PET/CT was superior in identifying pathological HIF-2α expression in primary tumors of RCC patients, demonstrating its potential application in predicting responses to HIF-2α antagonists. • [68Ga]Ga-PSMA-11 PET/CT could potentially predict the HIF-2α expression of primary tumors among patients with RCC. • SUVmaxof [68Ga]Ga-PSMA-11 PET/CT was the most significant predictor of HIF-2α expression level. • This probability could help predict the therapeutic response of patients with RCC to HIF-2α antagonists.

Meng L ，Zhang S ，Gao J ，Xu Q ，Fu Y ，Zhou YH ，Wang F ，Guo H ... -  《-》

(68)Ga-PSMA-11 PET/CT Parameter Correlates with Pathological VEGFR-2/PDGFR-β Expression in Renal Cell Carcinoma Patients.

Response prediction is necessary for renal cell carcinoma (RCC) tumors. We aim to evaluate parameters derived from 68 Ga-PSMA-11 PET/CT images for prediction of pathological VEGFR-2/PDGFR-β expression of primary RCC tumors. Forty-eight RCC patients were retrospectively enrolled with preoperative 68 Ga-PSMA-11 PET/CT scan and surgical specimen. Radiological parameters including tumor diameter, mean CT value, and maximal standard uptake value (SUVmax) were derived from PET/CT images and pathological VEGFR-2/PDGFR-β/PSMA expression were identified with immunohistochemistry. Mann-Whitney U test was performed for continuous variables and the chi-square test for categorical variables. ROC was used for determining the effectiveness of preoperative parameters in differentiating VEGFR-2/PDGFR-β expression. Univariate and multivariate logistic regression analyses were performed for significant parameters to predict VEGFR-2 & PDGFR-β co-expression. Of the 48 tumors, 25 (52.1%) harbored positive VEGFR-2 expression, 28 (58.3%) harbored positive PDGFR-β expression, and 24 (50%) were both VEGFR-2 positive and PDGFR-β positive. SUVmax significantly differed by subgroups of VEGFR-2/PDGFR-β expression (both P < 0.001). SUVmax demonstrated superior performance for differentiating VEGFR-2 & PDGFR-β co-expression (positive vs. negative), with area under the curve 0.87 (95% CI 0.78-0.96, P < 0.001), sensitivity 93% and specificity 78%. Moreover, SUVmax was identified as the significant predictor for VEGFR-2 & PDGFR-β co-expression (odds ratio 4.01, 95% CI 1.99-8.08, P < 0.001). Concordant with radiological findings with 68 Ga-PSMA-11 PET/CT, pathological PSMA staining intensity was significantly higher in both VEGFR-2-positive tumor and PDGFR-β-positive tumor (P = 0.009 and P < 0.001, respectively). 68 Ga-PSMA-11 PET/CT could effectively identify pathological VEGFR-2/PDGFR-β expression of primary RCC tumors, which may help with selection of mRCC patients suitable for TKIs treatment.

Gao J ，Meng L ，Xu Q ，Zhao X ，Deng Y ，Fu Y ，Guo S ，He K ，Shi J ，Wang F ，Zhang S ，Guo H ... -  《-》

[(68)Ga]Ga‑LNC1007 PET/CT in the evaluation of renal cell carcinoma: comparison with 2-[(18)F]FDG/[(68)Ga]Ga-PSMA PET/CT.

To compare the potential efficiency of [68Ga]Ga-LNC1007 with 2-[18F]FDG/[68Ga]Ga-PSMA PET/CT for detecting renal cell carcinoma (RCC) and to explore parameters derived from [68Ga]Ga-LNC1007 PET/CT for discriminating pathological characteristics in RCC. Twenty-five RCC patients confirmed by pathology were enrolled in this prospective study. The maximum standardized uptake value (SUVmax), mean SUV (SUVmean), gross tumor volume (GTV) and total lesion-tracer (TL-tracer) of lesions were calculated from the corresponding PET/CT images. Pathological characteristics included World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade and adverse pathological features (tumor necrosis or sarcomatoid or rhabdoid feature). [68Ga]Ga-LNC1007 PET/CT showed a higher detection rate for primary lesions than 2-[18F]FDG and [68Ga]Ga-PSMA (LNC1007 vs. FDG: 13/17 vs. 4/17, P = 0.005; LNC1007 vs. PSMA: 9/11 vs. 6/11, P = 0.361). [68Ga]Ga-LNC1007 PET/CT showed higher SUVmax (6.6 vs. 3.7, P = 0.005), SUVmean (4.1 vs. 2.3, P = 0.001) and TBR (2.6 vs. 1.7, P = 0.011) compared with 2-[18F]FDG PET/CT, and it also showed higher TBR (2.9 vs. 0.5, P = 0.003), TBR-delay (2.8 vs. 0.3, P = 0.003), GTV (84.1 vs. 42.9, P = 0.003) and TL-tracer (442.7 vs. 235.8, P = 0.008) compared with [68Ga]Ga-PSMA PET/CT. SUVmax and TBR derived from [68Ga]Ga-LNC1007 PET/CT could effectively differentiate WHO/ISUP grade (3-4 vs. 1-2) and adverse pathological features (positive vs. negative) (SUVmax: AUC 0.81, P = 0.04; AUC 0.80, P = 0.033; TBR: AUC 0.84, P = 0.026; AUC 0.85, P = 0.014). The SUVmax was positively correlated with the FAP expression, integrin αvβ3 expression and the total expression of FAP and integrin αvβ3 (r = 0.577, P = 0.006, r = 0.701, P < 0.001, and r = 0.702, P < 0.001, respectively). [68Ga]Ga-LNC1007 is a promising tracer for RCC imaging and can effectively identify aggressive pathological characteristics of RCC.

Lin R ，Wang C ，Chen S ，Lin T ，Cai H ，Chen S ，Yang Y ，Zhang J ，Xu F ，Zhang J ，Chen X ，Zang J ，Miao W ... -  《-》

Comprehensive evaluation of (68)Ga-PSMA-11 PET/CT parameters for discriminating pathological characteristics in primary clear-cell renal cell carcinoma.

Gao J ，Xu Q ，Fu Y ，He K ，Zhang C ，Zhang Q ，Shi J ，Zhao X ，Wang F ，Guo H ... -  《-》

Potential role of (68)Ga-PSMA PET/CT in metastatic renal cell cancer: A prospective study.

Prostate-specific membrane antigen (PSMA), in addition to its utility in prostate cancer, is also an angiogenic imaging marker for hypervascular tumors like renal cell carcinoma (RCC). Our study aims to assess the potential role of 68Ga-PSMA-11 positron emission tomography (PET)/CT in metastatic RCC and compare it with contrast-enhanced computed tomography (CECT). Biopsy-proven RCC patients with known or suspected distant metastases who underwent 68Ga-PSMA-11 PET/CT for staging/restaging were prospectively recruited. Those patients who had undergone 18F-FDG PET/CT within six weeks of 68Ga-PSMA PET/CT were also included retrospectively for comparative analysis. A patient-based and lesion-based analysis was done to compare the lesion detection rates of CECT, 68Ga-PSMA-11 PET and 18F-FDG PET. PET-based quantitative parameters were also compared between both the PET modalities. Impact of baseline parameters on survival was assessed using Cox regression analysis. A p-value of < 0.05 was considered significant. Thirty-seven patients with median age 60 years ± 13 years (range = 26-76 years) were included in the study. Twenty-seven patients had clear cell (cc) RCC, six had papillary RCC (pRCC), and one each had an eosinophilic variant of ccRCC, collecting duct RCC, translocation RCC and poorly differentiated RCC. 68Ga-PSMA-11 PET performed better in detecting marrow and equivocal bone lesions and worse in detecting liver lesions compared to CECT. 68Ga-PSMA-11 PET-based angiogenic tumor burden estimation using Total Lesion-PSMA (TL-PSMA) and PSMA-Total volume (PSMA-TV) had a prognostic impact on the survival of patients. 68Ga-PSMA-11 PET also detected more lesions and showed significantly higher SUVmax than 18F-FDG PET. 68Ga-PSMA-11 PET/CT performs better than CECT and 18F-FDG PET/CT in metastatic evaluation and has prognostic value in the management of clear cell RCC.

Aggarwal P ，Singh H ，Das CK ，Mavuduru RS ，Kakkar N ，Lal A ，Gorsi U ，Kumar R ，Mittal BR ... -  《-》