Correlation of 99mTc-sestamibi uptake in renal masses with mitochondrial content and multi-drug resistance pump expression

Steven P Rowe; Michael A Gorin; Lilja B Solnes; Mark W Ball; Ajuni Choudhary; Phillip M Pierorazio; Jonathan I Epstein; Mehrbod S Javadi; Mohamad E Allaf; Alex S Baras

doi:10.1186/s13550-017-0329-5

Correlation of ^99mTc-sestamibi uptake in renal masses with mitochondrial content and multi-drug resistance pump expression

EJNMMI Res. 2017 Oct 2;7(1):80. doi: 10.1186/s13550-017-0329-5.

Authors

Steven P Rowe^{1

2}, Michael A Gorin^{3

4}, Lilja B Solnes³, Mark W Ball⁴, Ajuni Choudhary⁵, Phillip M Pierorazio⁴, Jonathan I Epstein⁵, Mehrbod S Javadi³, Mohamad E Allaf⁴, Alex S Baras⁵

Affiliations

¹ The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD, 21287, USA. srowe8@jhmi.edu.
² The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. srowe8@jhmi.edu.
³ The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD, 21287, USA.
⁴ The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

Background: ^99mTc-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has recently been explored for the characterization of indeterminate renal masses. As judged by increased intra-tumoral radiotracer uptake, we have previously reported the excellent diagnostic performance characteristics of this test for identifying benign/indolent oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs). In this study, we investigated potential molecular mechanisms underlying the discriminatory ability of ^99mTc-sestamibi SPECT/CT for renal masses. Fifty renal masses imaged with ^99mTc-sestamibi SPECT/CT prior to surgical resection were evaluated by immunohistochemistry for mitochondrial content and expression of the multi-drug resistance pump 1 (MDR1/P-gp). Immunohistochemical staining was scored semi-quantitatively, and results were compared across renal tumor histologies and correlated with ^99mTc-sestamibi uptake.

Results: In total, 6/6 (100%) and 2/2 (100%) HOCTs demonstrated strong mitochondrial content staining combined with low MDR1 staining. Clear cell renal cell carcinoma showed an opposite pattern with the majority having low mitochondrial (14/26, 54%) and high MDR1 staining (18/26, 69%). Other tumor types were more variable in staining pattern, although the staining pattern reliably predicted ^99mTc-sestamibi uptake in almost all tumors except chromophobe renal cell carcinoma.

Conclusions: Our findings confirm that renal tumors with high mitochondrial content and relatively low MDR pump expression activity accumulate ^99mTc-sestamibi and allow for the accurate diagnosis of the benign/indolent tumor class that includes oncocytomas and HOCTs. For masses in which MDR activity outweighs the presence of mitochondria, the tumors appear cold on ^99mTc-sestamibi SPECT/CT, allowing for high confidence in the diagnosis of renal cell carcinoma.

Keywords: Oncocytoma; Renal cell carcinoma; SPECT/CT; Small renal mass.