Vol.

6, 2215, June 2000

Clinical Cancer Research 2125

Editorial

Molecular Imaging in Oncology: The Diagnostic Imaging Revolution

Steven M. Larson1
Nuclear Medicine Service, Memorial Sloan Kettering Cancer Center, New York, New York 10021 Table 1 Diagnostic imaging in oncology Detection Differential diagnosisa Tumor biology relevant to therapya Staging Recurrence Response to treatmenta
a

You cant make an omelet without breaking eggs. V. I. Lenin, early 20th century.

In the current issue of Clinical Cancer Research, Jager et al. (1) describe the imaging of soft tissue tumors using a novel radiopharmaceutical, L-3[iodine-123]iodo- -methyl-tyrosine, to image soft tissue sarcoma, based on single-photon emission computed tomography, a widely available nuclear medicine technique. The concentration of the radiopharmaceutical in the tumor was highly correlated with measures of proliferation including histological grade, mitotic index, tumor cellularity, and Ki-67 proliferation index. This study is an example of the emerging ability of noninvasive diagnostic imaging techniques to go beyond simple tumor detection to the characterization of important features of tumor biology. These new abilities of diagnostic imaging methods to detect and characterize tumor biology are best referred to as molecular imaging. Molecular imaging in oncology is the noninvasive imaging of the key molecules and molecular-based events that are fundamental to human tumor biology. The development of molecular imaging in oncology springs from the joining of two powerful forces. On the one hand, there has been an explosion of knowledge regarding tumor biology, particularly with regard to the molecular basis of cell cycle control and proliferation. On the other hand, there have been marvelous advances in imaging technology, based on improved electronics, greater computing power, better sensitivity and resolution, and new tracers for key molecules that facilitate cancer growth and development. Nuclear medicine techniques such as those described in this article lend themselves to molecular imaging. In fact, the basis for nuclear imaging in oncology is the use of biomolecular radiotracers to detect the living chemistry of tumors and normal tissues using radioactivity detectors. However, the concept of molecular imaging is not based on any single imaging technology. In fact, molecular imaging is protean in methodology but united by the common impulse to use an imaging parameter to infer qualitative or quantitative biochemical or functional information about human tumors and tissues. Over 20,000 articles in

Molecular imaging adds unique information.

Medline lay claim to molecular imaging as a component of their approach. Molecular imaging methods mentioned that are applicable to clinical medicine include gamma camera imaging, single-photon emission computed tomography, positron emission tomography, magnetic resonance spectroscopy, magnetic resonance imaging, optical imaging (macroscopic spectral imaging), and ultrasound. There is little question that molecular imaging is the basis for a revolution in diagnostic imaging and that this revolution has begun in oncology. This is because molecular imaging is meeting previously unmet diagnostic needs (see Table 1). For example, positron emission tomography imaging is now used throughout the country for the differential diagnosis of solitary pulmonary nodules in a way that both improves patient management and saves money (2). The potential improvements are very great; for example, magnetic resonance spectroscopy measurements of choline:citrate ratios in the prostate are likely to distinguish tumor from benign prostatic changes as a guide to biopsy and monitoring treatment response and recurrence (3). Like any revolution, there is a paradigm shift away from strictly anatomically based methods such as conventional X-ray and computed tomography toward in vivo methods for imaging biochemical changes in the cancer cell itself. In this case, the omelet in the quotation above is the molecular imaging approach to diagnosis, and the eggs are the old ways of thinking about anatomically based radiographic methodologies as the sole standard for diagnostic imaging in oncology.

References
1. Jager, P. L., Boudewijn, E. C. P., deVries, E. G. E., Molenaar, W. M., Vaalburg, W., Piers, A., and Hoekstra, H. J. Imaging of soft-tissue tumors using L-3[iodine-123]iodo- -methyl-tyrosine single-photon emission computed tomography: comparison with proliferative and mitotic activity, cellularity, and vascularity. Clin. Cancer Res., 6: 2252 2259, 2000. 2. Patz, E. J. Imaging lung cancer. Semin.Oncol., 5 (Suppl. 15): 2126, 1999. 3. Scheidler, J., Hricak, H., Vigneron, D. B., Yu, K. K., Sokolov, D. L., Huang, L. R., Zaloudek, C. J., Nelson, S. J., Carroll, P. R., and Kurhanewicz, J. Prostate cancer: localization with three-dimensional proton MR spectroscopy imaging-clinicopathologic study. Radiology, 213: 473 480, 1999.

Received 3/8/00; accepted 4/4/00. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 To whom requests for reprints should be addressed.