Molecular imaging in the era of personalized medicine

Abstract

Clinical imaging creates visual representations of the body interior for disease assessment. The role of clinical imaging significantly overlaps with that of pathology, and diagnostic workflows largely depend on both fields. The field of clinical imaging is presently undergoing a radical change through the emergence of a new field called molecular imaging. This new technology, which lies at the intersection between imaging and molecular biology, enables noninvasive visualization of biochemical processes at the molecular level within living bodies. Molecular imaging differs from traditional anatomical imaging in that biomarkers known as imaging probes are used to visualize target molecules-of-interest. This ability opens up exciting new possibilities for applications in oncologic, neurological and cardiovascular diseases. Molecular imaging is expected to make major contributions to personalized medicine by allowing earlier diagnosis and predicting treatment response. The technique is also making a huge impact on pharmaceutical development by optimizing preclinical and clinical tests for new drug candidates. This review will describe the basic principles of molecular imaging and will briefly touch on three examples (from an immense list of new techniques) that may contribute to personalized medicine: receptor imaging, angiogenesis imaging, and apoptosis imaging.

Keywords: Angiogenesis; Apoptosis; Individualized medicine; Molecular imaging; Receptor.

Fig. 1.

Similarity of molecular imaging and pathology in utilizing probes to contribute to personalized medicine.

Fig. 2.

Basic principles of molecular imaging. (A) Molecular imaging probes containing targeting components that interact with molecules-of-interest and signaling components that allow detection from outside of the body. (B) Representative small animal-dedicated molecular imaging devices that visualize signals emitted from probes within the living bodies of animal models. PET-CT, positron emission tomography–computed tomography; MRI, magnetic resonance imaging.

Fig. 3.

The overall process of molecular imaging research, which is similar to that of new drug development.

Fig. 4.

Example of tumor receptor imaging. (A) Quantum dot (QDot) probe surface-conjugated with epidermal growth factor (EGF) for targeting and radioisotopes for signaling. (B) A human breast cancer xenograft shows high probe uptake at baseline that is blocked by cetuximab therapy (Tx). (C) Tumor tissue sections show co-localization of fluorescent signals from the QDot with that from fluorescent-conjugated antibodies against EGF receptors (EGFR), indicating receptor-specific probe targeting.

Fig. 5.

Example of angiogenesis imaging. (A) Cyclic Arg-Gly-Asp (RGD) peptide probes can interrogate αvβ3 integrin receptors overexpressed on activated endothelial cells. (B–D) Examples of a xenografted tumor-bearing mouse model (B), a hindlimb ischemia mouse model (C), and a myocardial infarction rat model (D) showing increased uptake of radiolabeled RGD probes in lesions with angiogenesis.

Fig. 6.

Example of apoptosis imaging. (A) Annexin-V (AnxV) based probes target phosphatidyl serine exposed to the surface of cells that are undergoing apoptotic death. Here, AnxV is bound to streptavidin conjugated with PECy5.5 for fluorescent signaling. (B, C) In vivo fluorescent images of hindlimbs of living mice (supine with torso covered to block background signals; B) and ex vivo images of extracted tissue (C). Probe uptake is significantly increased in the ischemic hindlimb of the diabetic mouse due to apoptosis.