The Emerging Role of PET/CT with PSMA-Targeting Radiopharmaceuticals in Clear Cell Renal Cancer: An Updated Systematic Review

Simple Summary Positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals is a relatively novel technique currently employed in the management of prostate cancer patients. These radiopharmaceuticals target PSMA, also known as carboxypeptidase type II, which is mainly expressed by prostate cancer cells. Nevertheless, its expression has been observed in the neovasculature of various kinds of cancer, including clear cell renal cell carcinoma (ccRCC). Based on this biological mechanism, several authors postulated a potential role for this diagnostic method in ccRCC patients in different clinical settings. This systematic review provides an overview of the possible applications of PET/CT with PSMA-targeting radiopharmaceuticals in ccRCC. Abstract Background: Recent articles proposed the employment of positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals in clear cell renal cell carcinoma (ccRCC). Methods: The authors performed a comprehensive literature search of studies on the performance of PET/CT with PSMA-targeting radiopharmaceuticals in ccRCC. Original articles concerning this imaging examination were included in newly diagnosed ccRCC patients and ccRCC patients with disease recurrence. Results: A total of sixteen papers concerning the diagnostic performance of PSMA-targeted PET/CT in ccRCC (331 patients) were included in this systematic review. The included articles demonstrated an excellent detection rate of PSMA-targeting PET/CT in ccRCC. Conclusions: PSMA-targeted PET/CT seems promising in detecting ccRCC lesions as well as in discriminating the presence of aggressive phenotypes. Prospective multicentric studies are warranted to strengthen the role of PSMA-targeting PET/CT in ccRCC.

[1]  W. A. Noortman,et al.  Prostate-Specific Membrane Antigen Targeted Pet/CT Imaging in Patients with Colon, Gastric and Pancreatic Cancer , 2022, Cancers.

[2]  E. de Blois,et al.  Advances in 177Lu-PSMA and 225Ac-PSMA Radionuclide Therapy for Metastatic Castration-Resistant Prostate Cancer , 2022, Pharmaceutics.

[3]  N. Lawrentschuk,et al.  Impact of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in the Management of Oligometastatic Renal Cell Carcinoma , 2022, European urology open science.

[4]  G. Treglia,et al.  PSMA Radioligand Uptake as a Biomarker of Neoangiogenesis in Solid Tumours: Diagnostic or Theragnostic Factor? , 2022, Cancers.

[5]  F. Zhou,et al.  Special issue “The advance of solid tumor research in China”: 68Ga‐PSMA‐11 PET/CT for evaluating primary and metastatic lesions in different histological subtypes of renal cell carcinoma , 2022, International journal of cancer.

[6]  Jiong Shi,et al.  68Ga-PSMA-11 PET/CT Parameter Correlates with Pathological VEGFR-2/PDGFR-β Expression in Renal Cell Carcinoma Patients , 2022, Molecular Imaging and Biology.

[7]  A. Pearce,et al.  Characterization of tumor thrombus in renal cell carcinoma with prostate specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT). , 2022, Urologic oncology.

[8]  Jie Gao,et al.  [68Ga]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 , 2022, European Radiology.

[9]  R. Campi,et al.  PSMA PET/CT in Renal Cell Carcinoma: An Overview of Current Literature , 2022, Journal of clinical medicine.

[10]  U. Capitanio,et al.  European Association of Urology Guidelines on Renal Cell Carcinoma: The 2022 Update. , 2022, European urology.

[11]  L. Uccelli,et al.  Role of PSMA-ligands imaging in Renal Cell Carcinoma management: current status and future perspectives , 2022, Journal of Cancer Research and Clinical Oncology.

[12]  A. Jemal,et al.  Cancer statistics, 2022 , 2022, CA: a cancer journal for clinicians.

[13]  S. Hancock,et al.  Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. , 2022, Journal of the National Comprehensive Cancer Network : JNCCN.

[14]  A. Pearce,et al.  The role of dual tracer PSMA and FDG PET/CT in Renal Cell Carcinoma (RCC) compared to conventional imaging: A multi-institutional case series with intra-individual comparison , 2021, European Urology Open Science.

[15]  Kirsten L. Greene,et al.  Appropriate Use Criteria for Prostate-Specific Membrane Antigen PET Imaging , 2021, The Journal of Nuclear Medicine.

[16]  P. Seifert,et al.  PSMA-PET/CT in Patients with Recurrent Clear Cell Renal Cell Carcinoma: Histopathological Correlations of Imaging Findings , 2021, Diagnostics.

[17]  K. Rahbar,et al.  Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. , 2021, The New England journal of medicine.

[18]  E. Mayo-Wilson,et al.  The PRISMA 2020 statement: an updated guideline for reporting systematic reviews , 2021, BMJ.

[19]  P. Mulders,et al.  Targeted PET/CT imaging for clear cell renal cell carcinoma with radiolabeled antibodies: recent developments using girentuximab , 2021, Current opinion in urology.

[20]  N. Albert,et al.  18F-PSMA-1007 PET/CT for response assessment in patients with metastatic renal cell carcinoma undergoing tyrosine kinase or checkpoint inhibitor therapy: preliminary results , 2020, European Journal of Nuclear Medicine and Molecular Imaging.

[21]  A. Nadu,et al.  Dynamic 68Ga-PSMA-11 PET/CT for the Primary Evaluation of Localized Renal Mass: A Prospective Study , 2020, The Journal of Nuclear Medicine.

[22]  Baixuan Xu,et al.  Comparison of 18F-DCFPyL and 18F-FDG PET/computed tomography for the restaging of clear cell renal cell carcinoma: preliminary results of 15 patients , 2020, Nuclear medicine communications.

[23]  Jiong Shi,et al.  Comprehensive evaluation of 68Ga-PSMA-11 PET/CT parameters for discriminating pathological characteristics in primary clear-cell renal cell carcinoma , 2020, European Journal of Nuclear Medicine and Molecular Imaging.

[24]  J. Yaxley,et al.  The use of 68Ga-PET/CT PSMA in the staging of primary and suspected recurrent renal cell carcinoma , 2019, European Journal of Nuclear Medicine and Molecular Imaging.

[25]  H. Wester,et al.  PSMA-Targeted Radiopharmaceuticals for Imaging and Therapy. , 2019, Seminars in nuclear medicine.

[26]  W. Oyen,et al.  Lesion detection by [89Zr]Zr-DFO-girentuximab and [18F]FDG-PET/CT in patients with newly diagnosed metastatic renal cell carcinoma , 2019, European Journal of Nuclear Medicine and Molecular Imaging.

[27]  P. Choyke,et al.  PET imaging in renal cancer , 2019, Current opinion in oncology.

[28]  T. Klatte,et al.  Renal Cell Carcinoma with Sarcomatoid Features: Finally New Therapeutic Hope? , 2019, Cancers.

[29]  Xiaoping Zhou,et al.  Fructose 1,6-Bisphosphatase 1 Expression Reduces 18F-FDG Uptake in Clear Cell Renal Cell Carcinoma , 2019, Contrast media & molecular imaging.

[30]  F. Bray,et al.  Epidemiology of Renal Cell Carcinoma. , 2019, European urology.

[31]  Scott P. Campbell,et al.  Inconsistent Detection of Sites of Metastatic Non-Clear Cell Renal Cell Carcinoma with PSMA-Targeted [18F]DCFPyL PET/CT , 2018, Molecular Imaging and Biology.

[32]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[33]  W. Oyen,et al.  Positron Emission Tomography/Computed Tomography with 89Zr-girentuximab Can Aid in Diagnostic Dilemmas of Clear Cell Renal Cell Carcinoma Suspicion. , 2018, European urology.

[34]  C. Supuran,et al.  Carbonic anhydrase IX inhibition affects viability of cancer cells adapted to extracellular acidosis , 2017, Journal of Molecular Medicine.

[35]  Sam S. Chang,et al.  Optimal Surveillance Strategies After Surgery for Renal Cell Carcinoma. , 2017, Journal of the National Comprehensive Cancer Network : JNCCN.

[36]  G. Treglia,et al.  Systematic reviews and meta-analyses of diagnostic studies: a practical guideline , 2017, Clinical and Translational Imaging.

[37]  Charles Swanton,et al.  Renal cell carcinoma , 2017, Nature Reviews Disease Primers.

[38]  A. Shinagare,et al.  Update on Radiogenomics of Clear Cell Renal Cell Carcinoma. , 2016, European urology focus.

[39]  B. Hadaschik,et al.  F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients , 2016, European Journal of Nuclear Medicine and Molecular Imaging.

[40]  J. Preston,et al.  Pilot study: use of gallium-68 PSMA PET for detection of metastatic lesions in patients with renal tumour , 2016, EJNMMI Research.

[41]  J. McKenney,et al.  Tumor Necrosis Adds Prognostically Significant Information to Grade in Clear Cell Renal Cell Carcinoma: A Study of 842 Consecutive Cases From a Single Institution , 2016, The American journal of surgical pathology.

[42]  M. Ghosh,et al.  Prostate-specific membrane antigen (PSMA)-mediated laminin proteolysis generates a pro-angiogenic peptide , 2016, Angiogenesis.

[43]  P. Humphrey,et al.  The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. , 2016, European urology.

[44]  M. Pomper,et al.  [(18)F]Fluoroethyl Triazole Substituted PSMA Inhibitor Exhibiting Rapid Normal Organ Clearance. , 2016, Bioconjugate chemistry.

[45]  S. Girgis,et al.  Review of renal cell carcinoma and its common subtypes in radiology. , 2016, World journal of radiology.

[46]  W Marston Linehan,et al.  New Strategies in Renal Cell Carcinoma: Targeting the Genetic and Metabolic Basis of Disease , 2015, Clinical Cancer Research.

[47]  J. McKenney,et al.  Rhabdoid Differentiation Is Associated With Aggressive Behavior in Renal Cell Carcinoma: A Clinicopathologic Analysis of 76 Cases With Clinical Follow-up , 2014, The American journal of surgical pathology.

[48]  H. Hricak,et al.  Radiogenomics of clear cell renal cell carcinoma: associations between CT imaging features and mutations. , 2013, Radiology.

[49]  W Marston Linehan,et al.  Genetic basis of kidney cancer: Role of genomics for the development of disease-based therapeutics , 2012, Genome research.

[50]  Susan Mallett,et al.  QUADAS-2: A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies , 2011, Annals of Internal Medicine.

[51]  W. Marston Linehan,et al.  Von Hippel-Lindau (VHL) Inactivation in Sporadic Clear Cell Renal Cancer: Associations with Germline VHL Polymorphisms and Etiologic Risk Factors , 2011, PLoS genetics.

[52]  Yiyan Liu,et al.  Physiology and pathophysiology of incidental findings detected on FDG-PET scintigraphy. , 2010, Seminars in nuclear medicine.

[53]  W. Linehan,et al.  The genetic basis of kidney cancer: a metabolic disease , 2010, Nature Reviews Urology.

[54]  P. A. Futreal,et al.  Interleukin-8 mediates resistance to antiangiogenic agent sunitinib in renal cell carcinoma. , 2010, Cancer research.

[55]  Wanling Xie,et al.  Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[56]  F. Waldman,et al.  Improved Identification of von Hippel-Lindau Gene Alterations in Clear Cell Renal Tumors , 2008, Clinical Cancer Research.

[57]  J. Cheville,et al.  Histologic coagulative tumor necrosis as a prognostic indicator of renal cell carcinoma aggressiveness , 2005, Cancer.

[58]  P. Albert,et al.  Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location , 2004, Human mutation.

[59]  W. Fair,et al.  Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen. , 1993, Cancer research.

[60]  M. Pomper,et al.  Improved identification of patients with oligometastatic clear cell renal cell carcinoma with PSMA-targeted 18F-DCFPyL PET/CT , 2019, Annals of Nuclear Medicine.

[61]  C. Porta,et al.  Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. , 2019, Annals of oncology : official journal of the European Society for Medical Oncology.

[62]  G. Murphy,et al.  Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients. , 1987, Anticancer research.