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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

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 medicinetechnique. 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 de-

tect 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 sensitiv-

ity 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 technol-ogy. 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 infor-

mation about human tumors and tissues. Over 20,000 articles in

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 emis-

sion tomography, magnetic resonance spectroscopy, magnetic

resonance imaging, optical imaging (macroscopic spectral im-

aging), 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 man-

agement and saves money (2). The potential improvements arevery great; for example, magnetic resonance spectroscopy meas-

urements 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 ap-

proach 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.

References1. 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-tissuetumors using L-3[iodine-123]iodo--methyl-tyrosine single-photonemission computed tomography: comparison with proliferative and mi-totic activity, cellularity, and vascularity. Clin. Cancer Res., 6: 22522259, 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., andKurhanewicz, J. Prostate cancer: localization with three-dimensionalproton MR spectroscopy imaging-clinicopathologic study. Radiology,213: 473480, 1999.

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

Table 1 Diagnostic imaging in oncology

DetectionDifferential diagnosisa

Tumor biology relevant to therapya

StagingRecurrenceResponse to treatmenta

a Molecular imaging adds unique information.

2125Vol. 6, 2215, June 2000 Clinical Cancer Research