Differentiation of renal oncocytoma from renal cell carcinoma by means of ⁹⁹Tc-Sestamibi SPECT/CT

Purpose: An increasing body of literature indicates the beneficial role of [99m]Tc-Sestamibi SPECT/CT in the non-invasive differentiation of renal oncocytoma (RO) from renal cell carcinoma (RCC). This thesis presents a comprehensive approach of [99m]Tc-Sestamibi SPECT/CT examination following the implementation of quantitative tools in addition to visual assessment. An additional aim is to explain the differences in [99m]Tc-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 [99m]Tc-Sestamibi SPECT/CT examination before nephrectomy or percutaneous kidney biopsy. Kidney tumours with increased [99m]Tc-Sestamibi uptake were classified as positive (Sestamibi positive). In contrast, those with equal or decreased [99m]Tc-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 non- tumoral kidney parenchyma that correlated with the histopathological results. Additional immunohistochemical investigation, in situ metabolomics profile characterisation and correlation of mitochondrial content with [99m]Tc-Sestamibi SPECT/CT data, were also performed.

Results: Visual assessment of [99m]Tc-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. [99m]Tc-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 [99m]Tc-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

I. 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 Research. 2017;7.
https://doi.org/10.1186/s13550-017-0278-z

II. Tzortzakakis A, Holstensson M, Hagel E, Karlsson M, Axelsson R. Intra- and 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.
https://doi.org/10.2967/jnmt.118.223297

III. 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. 2020;22:88–96.
https://doi.org/10.1016/j.euros.2020.11.001

IV. 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]