DIFFERENTIATION OF RENAL ONCOCYTOMA FROM RENAL CELL CARCINOMA BY MEANS OF 99MTC-SESTAMIBI SPECT/CT

Purpose: An increasing body of literature indicates the beneficial role of 99mTc-Sestamibi SPECT/CT in the non-invasive differentiation of renal oncocytoma (RO) from renal cell carcinoma (RCC). This thesis presents a comprehensive approach of 99mTc-Sestamibi SPECT/CT examination following the implementation of quantitative tools in addition to visual assessment. An additional aim is to explain the differences in 99mTc-Sestamibi uptake among the different RCC subgroups on histometabolomic grounds. Methods: 57 radiologically detected kidney tumours from 52 patients were included in the present thesis. Each participant underwent a 99mTc-Sestamibi SPECT/CT examination before nephrectomy or percutaneous kidney biopsy. Kidney tumours with increased 99mTc-Sestamibi uptake were classified as positive (Sestamibi positive). In contrast, those with equal or decreased 99mTc-Sestamibi compared to the ipsilateral non-tumoral kidney parenchyma were classified as negative (Sestamibi negative). Following the visual assessment, quantitative SUVmean and SUVmax measurements performed in the examined kidney tumour and the nontumoral kidney parenchyma that correlated with the histopathological results. Additional immunohistochemical investigation, in situ metabolomics profile characterisation and correlation of mitochondrial content with 99mTc-Sestamibi SPECT/CT data, were also performed. Results: Visual assessment of 99mTc-Sestamibi SPECT/CT examination resulted in a sensitivity of 82% whereas, the quantitative assessment showed a sensitivity of 64% regarding the preoperative characterisation of RO. 99mTc-Sestamibi SPECT/CT identifies a larger Sestamibi-positive tumour group containing RO, hybrid oncocytic chromophobe tumour (HOCT) and the majority of chromophobe RCC (chRCC). A discriminatory metabolomic signature was identified for Sestamibi positive Birt-Hogg-Dubè-associated HOCT vs other renal oncocytic tumours. Metabolomic differences were also found between Sestamibi positive and negative chRCCs. Conclusion: Sestamibi positive kidney tumours on SPECT/CT examination are possibly of benign nature. Quantitative assessment with SUV SPECT measurements did not improve the diagnostic performance of 99mTc-Sestamibi SPECT/CT. Sestamibi negative kidney tumours should be considered for surgery due to their possibly malignant nature. On the other hand, Sestamibi positive kidney tumours could be suited for biopsy and/or follow up according to surveillance protocols. LIST OF SCIENTIFIC PAPERS 1) Tzortzakakis A, Gustafsson O, Karlsson M, Ekström-Ehn L, Ghaffarpour R, Axelsson R. Visual evaluation and differentiation of renal oncocytomas from renal cell carcinomas by means of 99mTc-Sestamibi SPECT/CT. EJNMMI Res. EJNMMI Research; 2017;7. 2) Tzortzakakis A, Holstensson M, Hagel E, Karlsson M, Axelsson R. Intraand Interobserver Agreement of SUV SPECT Quantitative SPECT/CT Processing Software, Applied in Clinical Settings for Patients with Solid Renal Tumors. J Nucl Med Technol. 2019;47:258–62. 3) Papathomas T *, Tzortzakakis A *, Sun N *, Erlmeier F, Bozoky B, Kokaraki G, et al. In Situ Metabolomics Expands the Spectrum of Renal Tumours Positive on 99mTc-Sestamibi Single Photon Emission Computed Tomography / Computed Tomography Examination. Eur Urol Open Sci. European Association of Urology. ; 2020;22:88–96 4) Antonios Tzortzakakis, Thomas Papathomas, Ove Gustafsson, Stefan Gabrielson, Kiril Trpkov, Linnea Ekström-Ehn, Bela Bozoky, Wanzhong Wang, Alexandros Arvanitis, Maria Holstensson, Mattias Karlsson, Georgia Kokaraki, Eva Hagel, Rimma Axelsson. Differentiation of renal oncocytoma from renal cell carcinoma by means of 99mTc-Sestamibi SPECT/CT. (manuscript) CONTENTS