Renal cell carcinoma (RCC) represents 3% of adult malignancies and is the sixth most common cause of cancer-related death. With the von Hippel-Lindau (VHL) gene showing somatic mutations in more than 80% of the most common subtype – clear cell RCC (ccRCC) – hypoxia-inducible factor (HIF) signaling is a key pathway inducing RCC formation. The chemokine receptor CXCR4 is a canonical hypoxia-inducible factor (HIF) target. CXCR4 expression in renal cell carcinoma is associated with resistance to chemotherapy and kinase inhibitors. Furthermore, CXCR4-expression apparently has an impact on the metastatic potential of RCCs.
Kidney tumors of unknown dignity are a relevant – and often incidental - finding in patients suffering from polycystic kidney diseases such as autosomal dominant polycystic kidney disease (ADPKD). New modalities are urgently awaited to better evaluate the nature of tumors in order to spare the patient unnecessary surgery and loss of functional kidney tissue.
Recently introduced Ga68-Pentixafor PET/CT molecular imaging for the first time allows in vivo non-invasive characterization of CXCR4 expression in the living patient. This may be of high value not only in RCC to provide individualized information about the tumor prognosis and behavior but to further characterize unclear kidney tumors. Furthermore, it may allow to increase our understanding of tumor development and to provide information on eligibility for novel treatment options, designed to interact with the CXCR4- CXCL12 pathways.
The translation of knowledge about CXCR4 expression from basic science into clinical practice by using Ga68-Pentixafor PET/CT may help for the in vivo characterization of kidney tumors with regard to aggressiveness, heterogeneity, prognosis, metastatic potential, therapy resistance and eligibility for novel therapy approaches. This may be of particular value not only in patients suffering from RCC but in patients with unclear kidney tumors due to polycystic kidney diseases such as ADPKD.