Molecular Imaging of Renal Cell Carcinoma: A Comprehensive Review Chinonyerem Okoro, Annerleim Walton Diaz, W Marston Linehan, Peter L Choyke and Adam R Metwalli * Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA * Corresponding author: Adam R Metwalli, Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, Tel: 301-496-6353; Fax: 301-402-0922; E-mail: adam.metwalli@nih.gov Received date: 21 April 2014, Accepted date: 7 July 2014, Published date: 20 July 2014 Copyright: © 2014 Metwalli AR, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. Abstract Renal Cell Carcinoma (RCC) represents a significant cause of cancer related deaths in the United States and worldwide. Current conventional imaging modalities including Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) reveal high resolution images of structural abnormalities; but these same modalities often fail to provide the adequate accuracy, specificity and sensitivity for diagnosing RCC from benign lesions. This has prompted ongoing investigation of molecular imaging modalities as a non-invasive alternative to biopsy. Initial use of glucose-based imaging agents has proven insufficient for common RCC histologies which have led to the development of targeted radiotracers to improve sensitivity of these scans. Current trials are ongoing to characterize the best use of these new targeted agents. In addition, novel radiotracer agents to evaluate renal perfusion, renal tubular function are being created and investigated. Introduction Renal cell carcinoma In 2013 there were estimated to be 65,150 new cases of and 13,680 deaths due to cancer of the kidney and renal pelvis in the United States, representing about 4% of all cancers in adults [1]. Despite this, the worldwide incidence and mortality of kidney cancer has shown signs of stabilization when compared to the past two decades [2]. RCC originates from the renal tubules and can give rise to different histology types including oncocytoma, angiomyolipoma, papillary, chromophobe and clear cell renal carcinoma (ccRCC). Different morphologic and phenotypic characteristics as well as the associated metabolic and genetic derangements involved in each tumor help stratify these histologic RCC subtypes [3,4] of renal tumors of all sizes about 13% are benign (oncocytoma and angiomyolipoma) and about 87% are malignant (papillary, chromophobe and clear cell), with papillary type 1 and chromophobe carcinoma being relatively indolent with more limited metastatic potential whereas papillary type 2 and clear cell carcinoma typically are more aggressive with greater metastatic potential [4-6]. Among these malignant tumors, clear cell represents the most common histologic subtype followed by papillary and chromophobe [7]. The increased use of advanced cross-sectional imaging modalities has led to the incidental discovery of more renal tumors [8,9]. With the advent and wide proliferation of improved anatomical imaging such as CT scanning and MRI, the greatest increase in diagnosis of renal masses has been among tumors less than 4 cm in size [10]. Conventional imaging modalities currently in use for evaluation of patients with known renal lesions cannot accurately distinguish RCC from a solid benign lesion such as oncocytoma, creating a diagnostic and management dilemma for physicians. Furthermore, current imaging modalities cannot give information on metastatic potential or even intra-tumoral cellular proliferation. CT and MRI both have high sensitivity but limited specificity for diagnosing RCC and identifying lesions best managed with surgery as opposed to surveillance [11,12]. Ultrasound or CT guided biopsies represent alternative methods of sampling tumor specimens in order to accurately diagnosis RCC, however these methods are invasive, have a small but clinically relevant incidence of complications, and are non-diagnostic in 10-20% of cases (inversely correlated to tumor size) [13-16]. Furthermore it has been shown with small renal masses (SRMs) that up to 25% will be benign if biopsied [14,16]. In addition, the rate of metastasis for SRMs has been shown to be very low thus Active Surveillance (AS) has become increasingly more accepted as a therapeutic option in addition to surgery or ablation [17,18]. However, finding the balance between the risk of intervention and the risk of potential metastases has been the difficult challenge in the management of SRMs. In light of the limitations of current imaging and biopsies, better non-invasive methods of diagnosing the RCC variants with the greatest malignant potential are needed. Molecular imaging of RCC holds promise in potentially yielding more information than currently available conventional imaging modalities, and the current targets and results of molecular imaging research in RCC will be reviewed. Positron Emission Tomography FDG-PET in renal cell carcinoma Positron Emission Tomography (PET) is a nuclear medicine technique based on the detection and quantification of radiation levels emitted from radiotracers attached to metabolic substrates or receptor ligands. These agents are used to provide information regarding a tumor’s biological features such as cell proliferation, metabolism and hypoxia [19,20] [18F]–fluorodeoxyglucose (FDG) is the most commonly used PET radiotracer for oncologic PET imaging [21]. Similar to glucose, FDG is transported into the cell and phosphorylated by a hexokinase. However, it is not metabolized any further and accumulates within the cell. Because tumors are typically more dependent upon glucose metabolism for energy as described by Warburg et al [22], as well as the fact that tumor cells generally have higher metabolic rates as a consequence of uncontrolled proliferation, Okoro et al., J Mol Genet Med 2014, 8:2 DOI: 10.4172/1747-0862.1000117 Review Article Open Access J Mol Genet Med ISSN:1747-0862 JMGM, an open access journal Volume 8 • Issue 2 • 1000117 Journal of Molecular and Genetic Medicine J o u r n a l o f M o l e c u l a r a n d G e n e t i c M e d i c i n e ISSN: 1747-0862