Elsevier

PET Clinics

Volume 4, Issue 1, January 2009, Pages 17-38
PET Clinics

PET Imaging of Angiogenesis

https://doi.org/10.1016/j.cpet.2009.04.011Get rights and content

This article reviews the application of PET in angiogenesis imaging at both the functional and molecular level. Angiogenesis is a highly-controlled process that is dependent on the intricate balance of both promoting and inhibiting factors, involved in various physiologic and pathologic processes. A comprehensive understanding of the molecular mechanisms that regulate angiogenesis has resulted in the design of new and more effective therapeutic strategies. Because of insufficient sensitivity to detect therapeutic effects by using standard clinical end points or by looking for physiologic improvement, a multitude of imaging techniques have been developed to assess tissue vasculature on the structural, functional, and molecular level. All the methods discussed have been successfully used pre-clinically and will hopefully aid in anti-angiogenic drug development in animal studies.

Section snippets

Biology of angiogenesis

The whole angiogenesis process involves several steps, including the growth of endothelial sprouts from pre-existing postcapillary venules and following the growth and remodeling process of the primitive network into a complex network.14 The cellular and molecular mechanisms of angiogenesis differ in various tissues and physiologic or pathologic angiogenesis.15 This section gives a brief introduction of tumor angiogenesis.

Each solid malignancy starts as a small population of transformed cells

Structural imaging of vasculature/angiogenesis

All imaging modalities can provide structural information, although they have different spatial resolution. The old-fashioned way for vascular structure imaging is X-ray angiography. However, it is difficult to provide microvasculature information. Following the steps of improvement of imaging equipments, contrast agents, and data acquisition and analysis techniques, more detailed vascular structure was deciphered. Several modalities are available for tumor microvascular imaging, including

Functional imaging of vasculature

The major consequence of angiogenesis is to perfuse and oxygenate surrounding tissue; therefore, the angiogenic process can be assessed by the evaluation of standard physiologic parameters, such as regional perfusion, function, and metabolism. During antiangiogenic or proangiogenic therapies, the changes in hemodynamic parameters can also be promising biomarkers for evaluating the therapeutic effect along with morphologic changes. Traditionally, tumor angiogenesis and antiangiogenic therapy

PET imaging

So far, PET is the most sensitive and specific technique for imaging molecular pathways in vivo in humans.85 PET radiotracers are physiologically and pharmacologically relevant compounds labeled with positron-emitting radioisotopes (such as fluoride-18 or carbon-11). After internalization by injection or inhalation, the tracer reaches the target and the location and the quantity is then detected with a PET scanner. With a ring-shaped array of photoelectric crystals, PET detectors capture

Summary and perspective

Numerous imaging techniques are available for assessing tissue vasculature on a structural, functional, and molecular level. A wide variety of targeting ligands (small molecules, peptides, peptidomimetics, and antibodies) have been conjugated with various imaging labels for MR imaging, US, optical, SPECT, PET, and multimodality imaging of angiogenesis. All these methods have been successfully used preclinically and will hopefully aid in antiangiogenic drug evaluation in animal studies. Because

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    Some of the research presented in this article was supported in part by the National Institute of Biomedical Imaging and Bioengineering (R21 EB001785), National Cancer Institute (R21 CA102123, P50 CA114747, U54 CA119367, and R24 CA93862), Department of Defense (W81XWH-04-1-0697, W81XWH-06-1-0665, W81XWH-06-1-0042, and DAMD17-03-1-0143), and a Department of Defense Prostate Postdoctoral Fellowship from Department of Defense (to G.N.)

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