Limited Utility of Quantitative Thresholds on 99mTc-Sestamibi Single-Photon Emission Computed Tomography/Computed Tomography for Distinguishing Renal Cell Carcinoma From Oncocytic Renal Masses

Purpose: 99m Tc-sestamibi single-photon emission CT/x-ray CT (SPECT/CT) uses a mitochondria-targeting tracer to differentiate renal cell carcinoma from oncocytomas and hybrid oncocytoma/chromophobe tumors. Initial studies support 99m Tc-sestamibi SPECT/CT’s accuracy, but we previously found that oncocytomas still account for 20% of lesions with low tracer uptake in qualitatively interpreted scans. Here, we assess performance of 99m Tc-sestamibi SPECT/CT utilizing quantitative assessment thresholds, hypothesizing that this may improve test performance. Materials and Methods: All 99m Tc-sestamibi SPECT/CT performed for renal mass evaluation between February 2020 and December 2021 was analyzed. A “hot” mass had qualitatively equivalent or higher 99m Tc-sestamibi uptake than normal renal parenchyma; a “cold” mass did not. Target-to-background ratios (TBRs) were calculated using tracer counts in the masses vs nearby normal parenchyma. Quantitative “hot”/“cold” determinations were made using published TBR cutoffs. Findings were correlated with histology. Results: Seventy-eight patients underwent 99m Tc-sestamibi SPECT/CT for 98 renal masses. For the 52 masses with diagnostic pathology, the negative predictive value (NPV) of qualitatively interpreted 99m Tc-sestamibi SPECT/CT for ruling out oncocytoma was 80%, with a 1.9% false-positive rate. A TBR cutoff of 0.46 achieved the highest NPV of 89.3%, with a 23.1% false-positive rate. A TBR cutoff of 0.74 achieved the lowest false-positive rate of 1.9%, with a 78.3% NPV. No TBR cutoff achieved both higher NPV and lower false positives than the qualitatively interpreted scans. Conclusions: Quantitative TBR cutoffs for interpretation of 99m Tc-sestamibi SPECT/CT scans for renal masses do not offer meaningful improvements in accuracy over qualitative reads. Additional studies are required to better characterize the utility of 99m Tc-sestamibi SPECT/CT in the real-world setting.