SNMMI/EANM/ACNM Procedure Standard/Procedure Guideline on the Use of Molecular Imaging for Renal Mass Characterization

Anatomic imaging of renal masses provides limited information on the histology or likely aggressiveness of the tumor, leading to the use of invasive procedures such as renal mass biopsy or empiric partial or radical nephrectomy. Molecular imaging can assist in risk stratification of indeterminate renal masses, potentially contributing to optimal patient decision-making. Two primary approaches have been explored for renal mass molecular imaging. The first is the use of agents that target carbonic anhydrase IX (CAIX), a cell-surface protein that is over-expressed on clear cell renal cell carcinoma (ccRCC) and generally not expressed on other renal tumors. A recent phase III trial (ZIRCON) is widely believed to have laid the groundwork for United States Food and Drug Administration approval of the CAIX monoclonal antibody ⁸⁹Zr-girentuximab. The second approach is the use of mitochondrial imaging agents, most notably ^99mTc-sestamibi, which are lipophilic cations that accumulate in tumors with an abundance of mitochondria with negative charge potential (e.g., oncocytomas and other benign/indolent lesion) and do not accumulate in tumors with multidrug resistance pumps (e.g., ccRCC). The complementary information from ⁸⁹Zr-girentuximab and ^99mTc-sestamibi can provide improved risk stratification. Further, emerging new targeted radiotracers and techniques such as imaging biomarker discovery with artificial intelligence will bolster those concepts. In this manual, we synthesize key data into a recommended approach.