Abstract
2694
Introduction: This educational exhibit aims to present the metabolic pathways that contribute to different subtypes of renal cell carcinoma (RCC). Additionally, radiotracers and the molecular mechanisms underlying their ability to detect specific cancer subtypes will be explored. Recognizing the downstream effects of metabolic alterations lays the groundwork for future PET imaging and pharmaceutical therapies in RCC subtypes.
Renal Cell Carcinomas (RCCs) are a collection of different cancers with distinct metabolic pathways, histologies, clinical courses, and treatment regimens. Subtypes of renal cell carcinoma are examined through the lens of their metabolic pathways concerning positron emission tomography (PET) imaging targets. The current state and future potential of PET radiotracers for imaging of these entities are reviewed.
Methods: Molecular pathways, cellular cascades, enzymes, and mutations that are involved in some of the most common subtypes of RCC were reviewed. Current evidence on specific radiotracers that target these metabolic pathways and enable molecular imaging of these RCC subtypes was investigated.
Results: Through this exhibit, we demonstrate the various molecular pathways of RCC. Potential radiotracers that target these pathways are identified. Similarities and distinguishing characteristics of these radiotracers are evaluated when applicable.
Hypoxia molecular pathway in the setting of RCC
Cellular response to hypoxia
Hypoxia-induced proteins
Tumor microenvironment alterations resulting from hypoxia
Tumor microenvironment changes that induce hypoxia
Transformations in tumor cells
Pathway in von Hippel-Lindau (VHL)-mutant clear cell RCC (Figure 1)
Transformations surrounding tumor cells
Tracers targeting this pathway
Specific markers of hypoxic cells, proteins, and enzymes within the hypoxia pathway
Markers of carbonic anhydrase IX (CAIX): Zr-89-girentuximab and 18F-VM4-037, Iodine (124I)-girentuximab, 18F-VM4-037, Grawitz250
Markers of hypoxic cells: 64Cu-diacetyl bis (N4-methylthiosemicarbazone) (Cu-ATSM), 124I-Iodo-Azomycin Galacto-Pyranoside (IAZGP), Fluoroazomycin arabinoside (18F-FAZA), and 18F-fluoromisonidazole (18F-FMISO).
Glucose metabolism molecular pathway in the setting of RCC
Mutation of succinate dehydrogenase (SDH) leading to SDH deficiency in the setting of renal pheochromocytoma and paraganglioma (PPGL)
Tracers targeting this pathway
Mutation of Krebs Cycle enzymes such as fumarate hydratase (FH) in the setting of Hereditary leiomyomatosis and renal cell cancer (HLRCC)
Radiotracers targeting this pathway:
TCA Cycle activity tracer: AC, 18F-fluoroacetate
Anaerobic metabolism tracers: 18F-fluorocholine, 11C-choline
18F-FDG PET as a marker of cellular glucose uptake used for papillary RCC imaging.
Mutation of Folliculin (FLCN) gene in the setting of Birt-Hogg-Dubé syndrome (BHD)
Radiotracers for this pathway (ie, 18F-DCFPyL-PSMA)
Angiogenesis pathway in and in RCC subtypes
Vascular endothelial growth factor (VEGF) pathway
VEGF-A-targeting radiotracer: 89Zr-Bevacizumab
Expression of Prostate-specific membrane antigen (PSMA) in RCC-associated neovasculature
PSAMA-targeting radiotracers: 18F-DCFPyL, CTT1057, [68Ga]P16-093.
Apoptosis pathways in RCC subtypes
Programmed cell death (PD L1) detection (ie, 89Zr-DFO-Atezolizumab)
Conclusions: Approaching RCC subtype treatment and radiotracers development requires a thorough understanding of the pathways that lead to their unique manifestations.