Editorial [Hot Topic: Imaging of Tumor Characteristics for Tailored Therapy (Executive Editor: Erik de Vries)]

Despite significant improvement in treatment efficacy, cancer is still a major cause of morbidity and mortality. The treatment of cancer patients is variable and it is more and more dependent on specific tumor characteristics, such as the expression of distinct receptors, enzymes and transcription factors. Usually these tumor characteristics are determined by biopsy of the primary tumor at diagnosis. In metastatic disease, however, tumor characteristics can be discordant between lesions in a single patient. Tumor characteristics can also changes during the course of the disease or in response to treatment. Consequently, some patients receive ineffective treatment, whereas other patients are withheld treatment that could have been effective. For optimal treatment decision-making, tumor characteristics should ideally be measured in all lesions throughout the course of the disease, but repeated biopsies of multiple lesions are not feasible in clinical practice. Nuclear imaging techniques, like PET and SPECT, offer the opportunity to repetitively and non-invasively monitor relevant biochemical and physiological parameters in patients. In the past decades, the clinical applications of these molecular imaging techniques in oncology have expanded from tumor detection and staging to therapy evaluation and imaging of specific tumor markers. Although the latter application of molecular imaging is still in its infancy, it could potentially improve therapy management by allowing clinicians to adjust treatment according to the specific tumor profile of the individual patient. With the introduction of expensive anti-cancer drugs, such as monoclonal antibodies, nuclear imaging also could help to control the vast increase in healthcare costs in developed countries by providing a tool for selection of patients that will actually benefit from these expensive therapies. Furthermore, imaging of specific tumor characteristics may not only be relevant for treatment management, but it might also aid drug development. Imaging would allow the selection of a homogenous study population and thus reduce the variation in clinical outcome. In addition, imaging of a specific tumor target could provide a suitable surrogate marker for determining the efficacy of a new drug. Such a surrogate marker may allow earlier and more sensitive prediction of drug efficacy than clinical tests of therapy outcome. In this thematic issue of Current Pharmaceutical Design, the developments in nuclear imaging of specific tumor characteristics that are relevant for clinical treatment decision-making and drug development are discussed. In the first article of this issue, Van der Veldt and coworkers discuss the mechanisms of anti-cancer drug resistance [1]. Drug resistance can be caused by multiple factors, like impaired drug delivery, metabolism or the absence of the drug target. Imaging with radiolabeled anticancer agents can help to reveal the cause of drug resistance and could allow selection of patients eligible to treatment. One of the phenomena associated with therapy resistance is hypoxia. Hypoxic tumors usually respond poorly to radiation therapy or chemotherapy. Several tracers for PET imaging of hypoxia have been developed. In the second article, Minn et al. give their view on the latest developments in imaging of hypoxia and discuss several factors that are important in the development of hypoxia markers [2]. Hypoxia is caused by insufficient blood supply to the tumor. Generation of new blood vessels (angiogenesis) is a prerequisite for tumor progression. Integrins are a family of adhesion molecules that play a pivotal role in the angiogenesis process. In the third review, Cai and coworkers give an overview of the field of imaging of angiogenesis and focus specifically on the development of radiopharmaceuticals for molecular imaging of integrins [3]. Several new drugs that inhibit tumor angiogenesis - and thus tumor growth - are approved for clinical use now. For optimal patient management, early monitoring of therapy efficacy is desirable. This is not only the case for anti-angiogenetic drugs, but for every kind of therapy. Programmed cell death (apoptosis) is the major elimination route of tumor cells that were successfully treated with radiation or chemotherapy. Thus, imaging of apoptosis could provide a useful tool for monitoring early treatment response. Radiopharmaceuticals that target extracellular phosphatidylserine exposure or the caspase-3 cascade in apoptotic cells are available now. An overview of the radiopharmaceuticals for nuclear imaging of apoptosis is presented in the paper by Blankenberg [4].