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Molecular Imaging Without Radiopharmaceuticals?

¹ Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee; ² Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee; ³ Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee; ⁴ Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee; ⁵ Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee; ⁶ Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee; ⁷ Department of Neurology, Vanderbilt University, Nashville, Tennessee; and ⁸ Department of Pharmacology, Vanderbilt University, Nashville, Tennessee

Correspondence: For correspondence or reprints contact: John C. Gore, Vanderbilt University, Institute of Imaging Science, 1161 21st Ave. South, AA 1105 MCN, Nashville, TN 37232-2310. E-mail: john.gore{at}vanderbilt.edu

The limitations on the sensitivity for detecting small changes in MRI, CT, and ultrasound pulse-echo images are used to estimate the practical requirements for molecular imaging and targeted contrast enhancement for these modalities. These types of imaging are highly unlikely to approach the sensitivity for detecting molecular processes of radionuclear methods, and the prospects for achieving sufficient concentrations of appropriate agents in vivo are poor for several types of applications such as small-molecule targeting of specific receptors. However, using relatively large carrier systems such as particles and liposomes, sufficient concentrations of paramagnetic agents may be delivered to achieve MR-signal changes adequate for detection. The use of higher-resolution MR images will aid the prospects for molecular imaging in small animals. Theoretic considerations also predict that a similar approach, using rather large particles or carriers of materials with a high atomic number, may also be successful for CT, especially with additional developments such as the use of monochromatic x-rays. The prospects of molecular imaging by x-ray imaging may not be as bleak as has been predicted. For ultrasound detection, gas-filled bubbles can provide a sufficient backscattered sound intensity to be detectable at concentrations and sizes not much different from agents designed for these other modalities.

Key Words: molecular imaging • MRI • x-ray CT • ultrasound

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