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

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Abstract

Background

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.

Methods

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.

Results

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).

Conclusion

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.

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Data Availability

The datasets during the current study is available from the corresponding author on reasonable request.

Abbreviations

AUC:

Area under the curve

CI:

Confidence interval

IHC:

Immunohistochemistry

mRCC:

Metastatic renal cell carcinoma

PET/CT:

Positron emission tomography/computed tomography

PDGFR:

Platelet-derived growth factor receptor

PSMA:

Prostate-specific membrane antigen

RCC:

Renal cell carcinoma

ROC:

Receiver operating characteristic curve

ROIs:

Regions of interest

SUVmax:

Maximal standard uptake value

TKIs:

Tyrosine kinase inhibitors

VEGFR:

Vascular endothelial growth factor receptor

WHO/ISUP grade:

World Health Organization/International Society of Urological Pathology grade

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Funding

This research was supported by the National Natural Science Foundation of China (ID: 81972388, 82103002), the Project of Invigorating Health Care through Science, Technology and Education, Jiangsu Provincial Key Medical Discipline (Laboratory) (ZDXKB2016014) and the Clinical Trials from the Affiliated DrumTower Hospital, Medical School of Nanjing University (2021-LCYJ-PY-23).

Author information

Author notes

  1. Jie Gao, Longxiyu Meng and Qinfeng Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Institute of Urology, Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, China

    Jie Gao, Longxiyu Meng, Xiaozhi Zhao, Yongming Deng, Kuiqiang He, Shiwei Zhang & Hongqian Guo

  2. Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Jiangsu, China

    Qinfeng Xu & Feng Wang

  3. Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Jiangsu, China

    Yao Fu & Jiong Shi

  4. School of Artificial Intelligence, Nanjing University, Jiangsu, China

    Suhan Guo

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  1. Jie Gao
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Contributions

J. Gao, L. Meng, and Q. Xu: contributed equally to project development, data collection, data analysis, and manuscript writing and editing; X. Zhao, Y. Deng, Su Guo, and K. He: data collection and analysis; F. Wang and S. Zhang: radiological analysis; Y. Fu and J. Shi: pathological analysis; H. Guo and S. Zhang: project development, data analysis, manuscript editing.

Corresponding authors

Correspondence to Shiwei Zhang or Hongqian Guo.

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Ethics Approval and Consent to Participate

The institutional review board (IRB) approval was obtained and all patients were informed and signed consent. The study protocol was approved by the Ethics Committee of the Drum Tower Hospital (2017–147-01).

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Patients were informed and signed consent for their individual person’s data to be used for publication.

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The authors declare that they have no conflict of interest.

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Gao, J., Meng, L., Xu, Q. et al. 68Ga-PSMA-11 PET/CT Parameter Correlates with Pathological VEGFR-2/PDGFR-β Expression in Renal Cell Carcinoma Patients. Mol Imaging Biol 24, 759–768 (2022). https://doi.org/10.1007/s11307-022-01725-1

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