The potential of molecular imaging, which allows the visualization of fundamental biomolecular and cellular processes, is both vast and largely unrealized. Nevertheless, molecular imaging at the preclinical level has already led to a greater understanding of the pathophysiologic mechanisms that underpin neoplasm and may eventually promote more effective drug development through early target validation, pharmacodynamic monitoring, and target patient selection. The development of molecular imaging in the clinical setting has only just begun and could yield tremendous patient benefit in the form of earlier lesion detection, treatment response monitoring, and a truly individualized approach to treatment of cancer.
Much of the impetus behind “personalized medicine” in oncology is based on the weakness of current therapeutic options. Standard therapies for neoplasm characteristically suffer from low response rates and substantial side effects due to systemic toxicity, particularly in the treatment of disseminated solid tumors. The promise of a personalized approach is tied to improving these therapies through uncovering the underlying molecular and cellular patho-physiologic processes that dictate therapeutic susceptibility. Early efforts in personalized medicine have resulted in targeted, pathway-specific therapeutics and, along with them, the possibility of discovering and tailoring treatments based on individual tumor susceptibilities. In vitro studies of neoplastic tissue receptor expression and single gene mutations for pretreatment testing is commonplace in breast cancer, where testing for human epidermal growth factor receptor (EGFR) 2 (HER2) overexpression is measured to determine trastuzumab treatment susceptibility [1
]. Similarly, testing for KRAS gene variants is required for testing EGFR antibody susceptibility and can additionally yield critical information in the use of EGFR kinase inhibitors [2
While there have been some early successes in leveraging diagnostics for improved treatment, current in vitro tests reflect only a part of the underlying cancer biology that leads to drug susceptibility; this is reflected, for example, in the 50% of HER2-overexpressing breast cancers that do not respond to trastuzumab [4
]. Advanced proteomic analysis, gene expression, and genome sequencing approaches are making headway in transitioning from the research setting to the clinical laboratory, but still need extensive validation before being clinically utilized to develop personalized therapies. Additionally, while advanced laboratory methods have promise for therapeutic planning purposes, monitoring response with repeated in vitro testing via biopsy is often impractical or impossible. In vitro material can be difficult to obtain and cancer adaptability and evolution over time can limit the utility of these studies. For example, histopathologic determination of the proportion of viable to nonviable cells after treatment correlates well with patient survival, but can only be applied to neoadjuvant therapies and cannot be repeated over time [5
Particularly as targeted therapies have become standard components of several cancer regimens, the ability to monitor the effect of these molecules clinically through noninvasive imaging techniques has become of great interest. Determination of nonresponders early in the therapeutic course through imaging critical molecular processes within cancer can lead to better treatment efficacy and fewer drug-related complications. Effective post-treatment evaluations can also give clinicians a means of targeting patients that need close follow-up. As it has become recognized that early determination of treatment efficacy is both critical for patient care and can be difficult or impossible to ascertain with current imaging methods, the evaluation of molecular biomarkers, noninvasively, at several points throughout the therapeutic course has served as the driving rationale for the development for many molecular imaging methods.
Several approaches for uncovering the cell-level effects of cancer therapy through molecular imaging have been developed and show promise as effective tools for tailoring and monitoring the therapeutic course. In this section we begin by briefly describing the current methods for monitoring clinical cancer response and then provide an overview of the most well-studied emerging molecular imaging techniques being developed for clinical cancer management.