Evaluation of [99mTc]Tc-HYNIC-PSMA-11 avidity in subtypes of renal cell carcinoma tumors

Document Type : Original Article

Authors

1 Nuclear Medicine Research Center, Mashhad University of Medical Science, Mashhad, Iran

2 Department of Urology, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Introduction: Renal cell carcinoma (RCC) is one of the most lethal urologic malignancies. The role of prostate-specific membrane antigen (PSMA) in prostate cancer is well known. PSMA has been shown in other tumors including renal cell carcinoma. [99mTc]Tc-HYNIC-PSMA-11 SPECT/CT is known as a cost effective alternative to [68Ga]Ga-PSMA in prostate cancer. We prospectively evaluated the bio-distribution and diagnostic role of 99mTc-HYNIC-PSMA SPECT/CT in patients with renal tumors before surgery; and also investigated whether the intensity of Tc-PSMA uptake will be different based on tumor histopathology.
Methods: 14 patients with primary renal tumors, clinically suspicious for RCC, underwent [99mTc]Tc-HYNIC-PSMA-11 SPECT/CT before surgery. All SPECT/CT images were reviewed separately. For quantitative analysis, volume of interest (VOI) was drawn over the tumor as well as the liver and maximum and mean counts were determined.
Results: In visual analysis, all renal lesions showed decreased uptake compared to the adjacent parenchymal tissue and liver. Whole body [99mTc]Tc-HYNIC-PSMA-11 scan in all cases could detect the region of tumoral lesion and the size and limits of the tumor were compatible with CT findings and histopathologic results. The ratio of maximum count of the tumor to the mean count of the liver showed no statistically significant difference between different subtypes (P value =0.50); however, the mean value was higher in clear renal cell RCC compared to non-clear cell RCC type (1.40 vs 1.23).
Conclusion: In our study, the low and inconsistent uptake of [99mTc]Tc-HYNIC-PSMA-11 in primary tumor of RCC suggest that this radiopharmaceutical is not an ideal agent for imaging this patient population.

Keywords

Main Subjects


  1. Znaor A, Lortet-Tieulent J, Laversanne M, Jemal A, Bray F. International variations and trends in renal cell carcinoma incidence and mortality. Eur Urol. 2015;67(3):519-30.
  2. Volpe A, Finelli A, Gill IS, Jewett MA, Martignoni G, Polascik TJ, Remzi M, Uzzo RG. Rationale for percutaneous biopsy and histologic characterisation of renal tumours. Eur Urol. 2012;62(3):491-504.
  3. Ahn T, Roberts MJ, Abduljabar A, Joshi A, Perera M, Rhee H, Wood S, Vela I. A review of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) in renal cell carcinoma (RCC). Mol Imaging Biol. 2019;21(5):799-807.
  4. Gao J, Xu Q, Fu Y, He K, Zhang C, Zhang Q, Shi J, Zhao X, Wang F, Guo H. Comprehensive evaluation of (68)Ga-PSMA-11 PET/CT parameters for discriminating pathological characteristics in primary clear-cell renal cell carcinoma. 2021;48(2):561-69.
  5. Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. N Engl J Med. 1996;335(12):865-75.
  6. Gupta K, Miller JD, Li JZ, Russell MW, Charbonneau C. Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev. 2008;34(3):193-205.
  7. Frank I, Blute ML, Cheville JC, Lohse CM, Weaver AL, Zincke H. Solid renal tumors: an analysis of pathological features related to tumor size. J Urol. 2003;170(6 Pt 1):2217-20.
  8. Kovacs G, Akhtar M, Beckwith BJ, Bugert P, Cooper CS, Delahunt B, Eble JN, Fleming S, Ljungberg B, Medeiros LJ, Moch H, Reuter VE, Ritz E, Roos G, Schmidt D, Srigley JR, Störkel S, van den Berg E, Zbar B. The Heidelberg classification of renal cell tumours. J Pathol. 1997;183(2):131-3.
  9. Golan S, Aviv T, Groshar D, Yakimov M, Zohar Y, Prokocimer Y, Nadu A, Baniel J, Domachevsky L, Bernstine H. Dynamic (68)Ga-PSMA-11 PET/CT for the Primary Evaluation of Localized Renal Mass: A Prospective Study. J Nucl Med. 2021;62(6):773-78.
  10. 1Pozzessere C, Bassanelli M, Ceribelli A, Rasul S, Li S, Prior JO, Cicone F. Renal Cell Carcinoma: the Oncologist Asks, Can PSMA PET/CT Answer? Curr Urol Rep. 2019;20(11):68.
  11. Loh J, Davis ID, Martin JM, Siva S. Extracranial oligometastatic renal cell carcinoma: current management and future directions. Future Oncol. 2014;10(5):761-74.
  12. Sánchez-Gastaldo A, Kempf E, González Del Alba A, Duran I. Systemic treatment of renal cell cancer: A comprehensive review. Cancer Treat Rev. 2017;60:77-89.
  13. Liu Y. The Place of FDG PET/CT in Renal Cell Carcinoma: Value and Limitations. Front Oncol. 2016;6:201.
  14. Lindenberg L, Mena E, Choyke PL, Bouchelouche K. PET imaging in renal cancer. Curr Opin Oncol. 2019;31(3):216-21.
  15. Gorin MA, Rowe SP, Allaf ME. Nuclear imaging of renal tumours: a step towards improved risk stratification. Nat Rev Urol. 2015;12(8):445-50.
  16. Khandani AH, Rathmell WK. Positron emission tomography in renal cell carcinoma: an imaging biomarker in development. Semin Nucl Med. 2012;42(4):221-30.
  17. Raveenthiran S, Esler R, Yaxley J, Kyle S. The use of (68)Ga-PET/CT PSMA in the staging of primary and suspected recurrent renal cell carcinoma. Eur J Nucl Med Mol Imaging. 2019;46(11):2280-88.
  18. Rowe SP, Gorin MA, Allaf ME, Pienta KJ, Tran PT, Pomper MG, Ross AE, Cho SY. PET imaging of prostate-specific membrane antigen in prostate cancer: current state of the art and future challenges. Prostate Cancer Prostatic Dis. 2016;19(3):223-30.
  19. Baccala A, Sercia L, Li J, Heston W, Zhou M. Expression of prostate-specific membrane antigen in tumor-associated neovasculature of renal neoplasms. Urology. 2007;70(2):385-90.
  20. Chang SS, Reuter VE, Heston WD, Gaudin PB. Metastatic renal cell carcinoma neovasculature expresses prostate-specific membrane antigen. Urology. 2001;57(4):801-5.
  21. Albalooshi B, Al Sharhan M, Bagheri F, Miyanath S, Ray B, Muhasin M, Zakavi SR. Direct comparison of (99m)Tc-PSMA SPECT/CT and (68)Ga-PSMA PET/CT in patients with prostate cancer. Asia Ocean J Nucl Med Biol. 2020;8(1):1-7.
  22. Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, Bolton D, Lawrentschuk N. Sensitivity, specificity, and predictors of positive (68)Ga-prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis. Eur Urol. 2016;70(6):926-37.
  23. Perera M, Murphy D, Lawrentschuk N. Prostate-specific membrane antigen positron emission tomography/computed tomography in locally advanced, recurrent, and metastatic prostate cancer. JAMA Oncol. 2018;4(5):748-49.
  24. Corfield J, Perera M, Bolton D, Lawrentschuk N. (68)Ga-prostate specific membrane antigen (PSMA) positron emission tomography (PET) for primary staging of high-risk prostate cancer: a systematic review. World J Urol. 2018;36(4):519-27.
  25. Udovicich C, Perera M, Hofman MS, Siva S, Del Rio A, Murphy DG, Lawrentschuk N. (68)Ga-prostate-specific membrane antigen-positron emission tomography/computed tomography in advanced prostate cancer: Current state and future trends. Prostate Int. 2017;5(4):125-29.
  26. Backhaus P, Noto B, Avramovic N, Grubert LS, Huss S, Bögemann M, Stegger L, Weckesser M, Schäfers M, Rahbar K. Targeting PSMA by radioligands in non-prostate disease-current status and future perspectives. 2018;45(5):860-77.
  27. Salas Fragomeni RA, Amir T, Sheikhbahaei S, Harvey SC, Javadi MS, Solnes LB, Kiess AP, Allaf ME, Pomper MG, Gorin MA, Rowe SP. Imaging of nonprostate cancers using psma-targeted radiotracers: rationale, current state of the field, and a call to arms. J Nucl Med. 2018;59(6):871-77.
  28. Evangelista L, Basso U, Maruzzo M, Novara G. The role of radiolabeled prostate-specific membrane antigen positron emission tomography/computed tomography for the evaluation of renal cancer. Eur Urol Focus. 2020;6(1):146-50.
  29. Spatz S, Tolkach Y, Jung K, Stephan C, Busch J, Ralla B, Rabien A, Feldmann G, Brossart P, Bundschuh RA, Ahmadzadehfar H, Essler M, Toma M, Müller SC, Ellinger J, Hauser S, Kristiansen G. Comprehensive evaluation of prostate specific membrane antigen expression in the vasculature of renal tumors: implications for imaging studies and prognostic role. J Urol. 2018;199(2):370-77.
  30. Urso L, Castello A, Rocca GC, Lancia F, Panareo S, Cittanti C, Uccelli L, Florimonte L, Castellani M, Ippolito C, Frassoldati A, Bartolomei M. Role of PSMA-ligands imaging in renal cell carcinoma management: current status and future perspectives. J. Cancer Res. Clin. Oncol. 2022;148(6):1299-311.
  31. Kinoshita Y, Kuratsukuri K, Landas S, Imaida K, Rovito PM Jr, Wang CY, Haas GP. Expression of prostate-specific membrane antigen in normal and malignant human tissues. World J Surg. 2006;30(4):628-36.
  32. Dumas F, Gala JL, Berteau P, Brasseur F, Eschwège P, Paradis V, Lacour B, Philippe M, Loric S. Molecular expression of PSMA mRNA and protein in primary renal tumors. Int J Cancer. 1999;80(6):799-803.
  33. Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997;3(1):81-5.
  34. Sawicki LM, Buchbender C, Boos J, Giessing M, Ermert J, Antke C, Antoch G, Hautzel H. Diagnostic potential of PET/CT using a (68)Ga-labelled prostate-specific membrane antigen ligand in whole-body staging of renal cell carcinoma: initial experience. Eur J Nucl Med Mol Imaging. 2017;44(1):102-07.