Elsevier

Advanced Drug Delivery Reviews

Volume 66, February 2014, Pages 90-100
Advanced Drug Delivery Reviews

Molecular imaging for cancer diagnosis and surgery

https://doi.org/10.1016/j.addr.2013.09.007Get rights and content

Abstract

Novel molecular imaging techniques have the potential to significantly enhance the diagnostic and therapeutic approaches for cancer treatment. For solid tumors in particular, novel molecular enhancers for imaging modalities such as US, CT, MRI and PET may facilitate earlier and more accurate diagnosis and staging which are prerequisites for successful surgical therapy. Enzymatically activatable “smart” molecular MRI probes seem particularly promising because of their potential to image tumors before and after surgical removal without re-administration of the probe to evaluate completeness of surgical resection. Furthermore, the use of “smart” MR probes as part of screening programs may enable detection of small tumors throughout the body in at-risk patient populations. Dual labeling of molecular MR probes with fluorescent dyes can add real time intraoperative guidance facilitating complete tumor resection and preservation of important structures. A truly theranostic approach with the further addition of therapeutic agents to the molecular probe for adjuvant therapy is conceivable for the future.

Introduction

In public discussion, improved drug treatment is often perceived as the main driver in the fight against cancer. However, in the case of solid tumors, early detection has to be considered equally, if not more important for successful treatment because it enables a surgical, curative approach. Surgery is usually limited to tumors detected at an early stage and outcomes decrease significantly once primary surgery is not a treatment option any more. For example, according to 2010 National Cancer Database (NCDB) data, 60% of stage I non-small cell lung cancer (NSCLC) patients had cancer removal surgery as their primary treatment, compared to just 6% diagnosed at stage III [1]. The 5-year survival rate for NSCLC patients whose cancer was surgically resected is 60–80% for stage I and 40–50% for stage II [2]. Concurrently, non-resectable stage III NSCLC treated with chemotherapy is associated with 2-year survival rates of less than 20% [3], emphasizing the importance of early detection and subsequent surgical removal.

Over the past decades, substantial efforts have been made to detect malignancies at an earlier state. Much of the progress made in cancer diagnostics and staging can be attributed to technical advances in ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI) which are essential for providing anatomic details for solid cancers [4]. Molecular imaging techniques may very well have the potential to improve every aspect of cancer care by opening up entirely new possibilities for the early detection and the effective treatment of cancer, both of which are essential to successfully fight the disease. Commonly and somewhat unspectacularly, molecular imaging is defined as non-invasive imaging of cellular and sub-cellular events [5]. More specifically, oncologic molecular imaging is based on highlighting distinctive molecular characteristics of malignant cells. Over the past years the genetically determined production of biomolecules by cancer cells has been extensively studied and characterized and individual expression profiles have been defined for certain types of cancer [6], [7]. Molecular imaging probes target and highlight these specific characteristics which can be exhibited either directly in, or on, individual malignant cells or in the surrounding extracellular matrix and cells in the vicinity, such as T cells, macrophages, dendritic cells, fibroblasts or endothelial cells [4].

Currently molecular imaging strategies for all major whole body imaging modalities for cancer diagnosis and staging as well as molecular imaging probes for optical imaging in cancer surgery are being developed [8], [9] (Table 1). These strategies give US, CT and MR an entirely new dimension by expanding morphological imaging to a cellular, functional level. Selective depiction of cellular properties and their microenvironments characteristic for the malignant state will enable earlier detection, assessment of aggressiveness and lead to a more personalized treatment approach.

Today, many clinicians still primarily associate molecular imaging with positron emission tomography (PET). Indeed, PET imaging with 18F-fluorodeoxyglucose (18F-FDG) depicts the metabolic discrepancies between malignant and healthy cells, making PET the first “true” and most widespread molecular imaging modality. However, its high cost, use of ionizing radiation, and relatively low spatial resolution somewhat restrict its potential. Therefore, molecular imaging with higher resolution modalities, especially MR, is gaining increasing attention. Aside from the whole body imaging applications, molecular imaging probes have also been adapted for optical imaging and can provide intraoperative guidance for cancer surgery. Ideally, molecular imaging probes will allow for earlier diagnostic imaging of solid cancers as well as facilitating better surgical treatment in the future, leading to an overall improved outcome. This review aims to outline relevant molecular imaging applications currently available or in development for the diagnosis, staging (CT, PET, US and MRI) and surgical treatment of cancers.

Section snippets

New levels of cancer diagnosis and staging

Based on their inherent characteristic of making functional attributes of malignant cells visible, molecular imaging techniques have the potential to enhance cancer diagnosis and staging on multiple levels, most notably tumor detection and characterization. While US, CT and MR imaging technology is continuously advancing, tumor detection today is still largely performed based on anatomical characteristics. Molecular imaging applications can make properties of carcinogenesis visible at much

Molecular imaging in cancer surgery

Advances in early diagnosis will allow more patients to pursue a surgical cure for cancer treatment. The main goal of cancer surgery is to identify and remove as much diseased tissue as possible while limiting damage to healthy tissue and structures. The standard of care in oncologic surgery currently relies on white light reflectance which limits the differentiation between normal and diseased tissue to a narrow palette between tissue colors and texture. Molecular imaging not only has the

Technical and logistical considerations

There is little doubt that molecular imaging technology has the potential to add substantial value to the diagnosis and surgical treatment of cancer. This section will address some substantial technical and logistical aspects which need to be taken into consideration on the path to wide-spread clinical use of molecular imaging probes. Key issues include probe design and imaging technology determining sensitivity and specificity which have been broached throughout this article and are briefly

Conclusion and outlook

Early detection, accurate staging and complete surgical removal are crucial in order to successfully treat and potentially cure patients with solid cancers. Molecular imaging techniques have the potential to play an important role in improving cancer diagnosis and treatment by expanding existing whole body imaging modalities to a functional, cellular level as well as enhancing intraoperative visualization of diseased and healthy tissues for surgeons. PET imaging has already established itself

Acknowledgement

This work was supported by Burroughs Wellcome Fund (CAMS) and R01 EB014929-01A1.

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