Insulin-like growth factor 1 receptor (IGF1R) plays an important role in proliferation, apoptosis, angiogenesis, and tumor invasion. Histology and in situ hybridization studies have revealed that IGF1R was significantly up-regulated at the protein and mRNA level in many types of cancer. Since measuring IGF1R expression with immunohistochemistry has many limitations, non-invasive imaging of IGF1R can allow for more accurate patient stratification (e.g. selecting the right patient population for IGF1R-targeted therapy) and more effective monitoring of the therapeutic responses in cancer patients. In this review, we will summarize the current status of imaging IGF1R expression in cancer, which includes single-photon emission computed tomography, positron emission tomography, fluorescence, and γ-camera imaging. The four major classes of ligands that have been developed for non-invasive visualization of IGF1R will be discussed: proteins, antibodies, peptides, and affibodies. To date, molecular imaging of IGF1R expression is understudied and more research effort is needed in the future.

Molecular imaging is an attractive modality that has been widely employed in many aspects of biomedical research; especially those aimed at the early detection of diseases such as cancer, inflammation and neurodegenerative disorders. The field emerged in response to a new research paradigm in healthcare that seeks to integrate detection capabilities for the prediction and prevention of diseases. This approach made a distinct impact in biomedical research as it enabled researchers to leverage the capabilities of molecular imaging probes to visualize a targeted molecular event non-invasively, repeatedly and continuously in a living system. In addition, since such probes are inherently compact, robust, and amenable to high-throughput production, these probes could potentially facilitate screening of preclinical drug discovery, therapeutic assessment and validation of disease biomarkers. They could also be useful in drug discovery and safety evaluations. In this review, major trends in the chemical synthesis and development of positron emission tomography (PET), optical and magnetic resonance imaging (MRI) probes are discussed.

Apoptosis is a mode of programmed cell death in multicellular organisms and plays a central role in controlling embryonic development, growth and differentiation and monitoring the induction of tumor cell death through anticancer therapy. Since the most effective chemotherapeutics rely on apoptosis, imaging apoptotic processes can be an invaluable tool to monitor therapeutic intervention and discover new drugs modulating apoptosis. The most attractive target for developing specific apoptosis imaging probes is caspases, crucial mediators of apoptosis. Up to now, various optical imaging strategies for apoptosis have been developed as an easy and economical modality. However, current optical applications are limited by poor sensitivity and specificity. A subset of molecular imaging contrast agents known as “activatable” or “smart” molecular probes allow for very high signal-to-background ratios compared to conventional targeted contrast agents and open up the possibility of imaging intracellular targets. In this review, we will discuss the unique design strategies and applications of activatable probes recently developed for fluorescence and bioluminescence imaging of caspase activity.

111In-capromab pendetide is an imaging probe for noninvasive detection of prostate cancer dissemination, and can be difficult to interpret because of low photon statistics resulting in noisy images with limited anatomical precision. We examined if a 16-slice multidetector computed tomography (MDCT) combined with single photon emission computed tomography (SPECT) could increase the impact on the clinical management and improve confidence in SPECT image interpretations in comparison to a relatively low-mA (limited resolution) CT. 17 scans were reviewed from a SPECT combined with low-mA CT scanner; 21 scans were reviewed from a SPECT combined with 16-slice MDCT scanner. Reports of the clinical interpretations from the imaging studies, additional examinations performed by referring physicians as a follow-up to the imaging results, and long-term clinical and laboratory follow-ups were used to define confidence of the SPECT/CT readings and impact of the readings on the patient management. The impact was defined as: the occurrence of the 111In-capromab pendetide interpretation resulted in additional imaging studies or biopsies. MDCT improved the quality and confidence in the characterization of small lymph nodes with or without uptake of 111In-capromab pendetide. The increased confidence with MDCT in SPECT/CT readings was evident in all cases reviewed in this study, and the impact on the clinical management was higher (8 out of 21) using SPECT/MDCT than the impact using SPECT combined with low-mA CT (2 out of 17). The dual-modality SPECT/CT provides a quantifiable benefit when MDCT is used instead of low-mA CT, particularly for prostate cancer evaluations using 111In-capromab pendetide.

The pivotal role of vascular endothelial growth factor (VEGF) in cancer is underscored by the approval of bevacizumab (Bev, a humanized anti-VEGF monoclonal antibody) for first line treatment of cancer patients. The aim of this study was to develop a dual-labeled Bev for both positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging of VEGF. Bev was conjugated to a NIRF dye (i.e. 800CW) and 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) before 64Cu-labeling. Flow cytometry analysis of U87MG human glioblastoma cells revealed no difference in VEGF binding affinity/specificity between Bev and NOTA-Bev-800CW. 64Cu-labeling of NOTA-Bev-800CW was achieved with high yield. Serial PET imaging of U87MG tumor-bearing female nude mice revealed that tumor uptake of 64Cu-NOTA-Bev-800CW was 4.6 ± 0.7, 16.3 ± 1.6, 18.1 ± 1.4 and 20.7 ± 3.7 %ID/g at 4, 24, 48 and 72 h post-injection respectively (n = 4), corroborated by in vivo/ex vivo NIRF imaging and biodistribution studies. Tumor uptake as measured by ex vivo NIRF imaging had a good linear correlation with the %ID/g values obtained from PET (R2 = 0.93). Blocking experiments and histology both confirmed the VEGF specificity of 64Cu-NOTA-Bev-800CW. The persistent, prominent, and VEGF-specific uptake of 64Cu-NOTA-Bev-800CW in the tumor, observed by both PET and NIRF imaging, warrants further investigation and future clinical translation of such Bev-based imaging agents.

Non-invasive and quantitative imaging of tumor angiogenesis is essential for lesion detection, patient stratification, drug development, and personalized anti-cancer therapies. In particular, the right timing is critical for anti-angiogenic cancer therapy and non-invasive imaging can help determine whether to start and when to start such treatment. In this inaugural issue of the American Journal of Nuclear Medicine and Molecular Imaging, a peptoid-based positron emission tomography (PET) tracer was reported for imaging of VEGFR expression in a prostate cancer model. This important proof-of-principle study opened the door to a fertile area of research, which holds tremendous potential for various applications in future personalized medicine.

Successful reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) ushered in a new era of regenerative medicine. Human iPSCs provide powerful new approaches for disease modeling, drug testing, developmental studies, and therapeutic applications. Investigating iPSC behavior in vivo and the ultimate feasibility of cell transplantation therapy necessitates the development of novel imaging techniques to longitudinally monitor iPSC localization, proliferation, integration, and differentiation in living subjects. At this five year mark of initial iPSC discovery, we review the current status of imaging iPSCs which ranges from in vitro studies, where imaging was used to study the processes/mechanisms of cellular reprogramming, to in vivo imaging of the survival of transplanted cells. To date, most imaging studies of iPSCs have been based on optical techniques, which include fluorescence and bioluminescence imaging. Since each imaging technique has its advantages and limitations, a combination of multiple imaging modalities may provide complementary information. The ideal imaging approach for tracking iPSCs or their derivatives in patients requires the imaging tag to be non-toxic, biocompatible, and highly specific to reduce perturbation of these cells. In few other scenarios can “personalized medicine” be better illustrated than the use of individual patient-specific iPSCs. Much future effort will be required before this can become a reality and clinical routine, where imaging will play an indispensible role in many facets of iPSC-based research and therapies.