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The successful management of prostate cancer requires early detection, appropriate risk assessment, and optimum treatment. An unmet goal of prostate cancer imaging is to differentiate indolent from aggressive tumors, as treatment may vary for different grades of the disease. Different modalities have been tested to diagnose, stage, and monitor prostate cancer during therapy. This review briefly describes the key clinical issues in prostate cancer imaging and therapy and summarizes the various new imaging modalities and agents in use and on the horizon.

The intention of this review is to provide information about the rapidly evolving field of molecular imaging and its potential impact on the clinical practice of nuclear medicine. On completing this article the reader should be able to define molecular imaging, describe the ways in which molecular imaging can be used, identify some of the biologic processes that can be targeted with molecular imaging agents, and list the modalities that can be used for molecular imaging, along with the strengths and weaknesses of each.

A promising role of cellular therapies in cancer treatment is reflected by the constantly growing number of clinical trials with adoptively transferred cells. Direct and indirect cell labeling for the nuclear imaging of transferred cells has been proven reliable for imaging adoptive cellular therapies. Both methods show their advantages and limitations. Direct labeling is a relatively easy, inexpensive, and well-established methodology. Indirect labeling using a reporter gene imaging paradigm allows for reliable, stable, and harmless visualization of cellular trafficking, persistence, proliferation, and function at the target site. It is expected that new human-derived reporter genes will be rapidly translated into clinical applications that require repetitive imaging for the effective monitoring of various genetic and cellular therapies.

Nanotechnology is poised to transform research, prevention, and treatment of cancer through the development of novel diagnostic imaging methods and targeted therapies. In particular, the use of nanoparticles for imaging has gained considerable momentum in recent years. This review focuses on the growing contribution of quantum dots (QDs) for in vivo imaging in small-animal models. Fluorescent QDs, which are small nanocrystals (1-10 nm) made of inorganic semiconductor materials, possess several unique optical properties best suited for in vivo imaging. Because of quantum confinement effects, the emission color of QDs can be precisely tuned by size from the ultraviolet to the near-infrared. QDs are extremely bright and photostable. They are also characterized by a wide absorption band and a narrow emission band, which makes them ideal for multiplexing. Finally, the large surface area of QDs permits the assembly of various contrast agents to design multimodality imaging probes. To date, biocompatible QD conjugates have been used successfully for sentinel lymph node mapping, tumor targeting, tumor angiogenesis imaging, and metastatic cell tracking. Here we consider these novel breakthroughs in light of their potential clinical applications and discuss how QDs might offer a suitable platform to unite disparate imaging modalities and provide information along a continuum of length scales.

Molecular imaging is a rapidly emerging research tool and clinical discipline aimed at noninvasive, quantitative visualization of in vivo molecular processes occurring at cellular and subcellular levels. At present, advancement of the molecular imaging field is driven by the development of improved imaging hardware for use in preclinical and clinical settings, the identification and validation of new, biologically relevant imaging targets, and the development of improved imaging probes derived from novel chemistries. Of these 3 essential facets, which comprise a majority of current molecular imaging research, hardware development and novel target discovery significantly outpace the development and clinical advancement of new molecular imaging probes, particularly with respect to cancer imaging.

Immune system activation can be elicited in viral infections, active immunization, or cancer immunotherapy, leading to the final common phenotype of increased glycolytic use by immune cells and subsequent detection by 18F-FDG PET. Because 18F-FDG is also used in baseline staging PET/CT scans and in tumor response assessment, physicians are faced with a unique challenge when evaluating tumor response in patients receiving cancer immunotherapy. The burgeoning field of cancer immunotherapy and the paucity of PET probes that can reliably differentiate activated immune cells from metabolically active cancer cells underscore the pressing need to identify and develop additional molecular imaging strategies. In an effort to address this concern, investigators have taken several molecular imaging approaches for cancer immunotherapy. Direct ex vivo labeling of T lymphocytes with radioactive probes before reinfusion represents the earliest attempts but has proven to be clinically limited because of significant PET probe dilution from proliferation of activated immune cells. Another approach is the indirect in vivo labeling of immune cells via PET reporter gene expression and involves the ex vivo genetic engineering of T lymphocytes with a reporter gene, reinfusion into the host, and the subsequent use of a PET probe specific for the reporter gene. The most recent approach involves the direct in vivo labeling of immune cells by targeting endogenous immune cell biochemical pathways that are differentially expressed during activation. In conclusion, these novel PET-based imaging approaches have demonstrated promise toward the goal of in vivo, noninvasive immune monitoring strategies for evaluating cancer immunotherapy.

The objective of cardiac stress testing is to detect coronary artery disease (CAD) and to prevent future adverse events, such as myocardial infarction or death. The progression from electrocardiographically based stress testing to current SPECT and PET technologies has brought improvements in diagnostic efficacy and resolution. Myocardial perfusion imaging facilitates management of CAD in elective and acute settings by providing valuable diagnostic and prognostic information. Hybrid PET/CT and SPECT/CT systems impart complementary information of coronary anatomy and its physiologic significance on blood flow reserve. In the current era, diagnosis and treatment of cardiovascular disease is increasingly defined by underlying molecular and genomic aberrations rather than by clinical signs and symptoms alone. Nuclear imaging is uniquely primed to exploit the targeting of expressed cell-surface molecules and intracellular processes of cardiovascular disease and to foster the development of innovative therapeutic interventions in the future.

In this article, the current and potential clinical roles of (13)C magnetic resonance spectroscopy (MRS) and (13)C magnetic resonance spectroscopic imaging are presented, with a focus on applications to prostate cancer and hyperpolarized (13)C spectroscopic imaging. The advantages of (13)C MRS have been its chemical specificity and lack of background signal, with the major disadvantage being its inherently low sensitivity and the subsequent inability to acquire data at a high-enough spatial and temporal resolution to be routinely applicable in the clinic. The approaches to improving the sensitivity of (13)C spectroscopy have been to perform proton decoupling and to use endogenous (13)C-labeled or enhanced metabolic substrates. With these nominal increases in signal-to-noise ratio, (13)C MRS using labeled metabolic substrates has shown diagnostic promise in patients and has been approved by the Food and Drug Administration. The development of technology that applies dynamic nuclear polarization to generate hyperpolarized (13)C-labeled metabolic substrates, and the development of a process for delivering them into living subjects, have totally changed the clinical potential of MRS of (13)C-labeled metabolic substrates. Preliminary preclinical studies in a model of prostate cancer have demonstrated the potential clinical utility of hyperpolarized (13)C MRS.

Today's medical imaging technologies are expected to furnish anatomic, physiologic, molecular, and genomic information for accurate disease diagnosis, prediction of treatment response, and development of highly specific and sensitive drugs and imaging agents. However, none of the current imaging methods used in humans provides comprehensive medical imaging. To harness the strengths of different imaging methods, multimodality imaging has become an attractive strategy for in vivo studies. Beyond small-animal imaging, a less frequently used multimodality imaging strategy is the fusion of radionuclear and optical methods. This less frequent use is probably attributable to some misconceptions, technical difficulties, or a lack of appreciation for the benefits of the 2 methods in patient care. This minireview addresses some of these concerns, with emphasis on the potential applications of multimodality optical and SPECT/PET systems.