Novel Receptor-Targeted Fluorescent Contrast Agents for In... : Investigative Radiology (original) (raw)

Original Investigations

ACHILEFU, SAMUEL PhD*; DORSHOW, RICHARD B. PhD†; BUGAJ, JOSEPH E. MS*; RAJAGOPALAN, RAGHAVAN PhD†

From *Discovery Research and †Imaging R&D, Mallinckrodt Inc., St. Louis, Missouri.

Received March 29, 2000, and accepted for publication, after revision, May 11, 2000.

Reprint requests: Samuel Achilefu, PhD, Mallinckrodt, Inc., 675 McDonnell Blvd., St. Louis, MO 63042; e-mail: [email protected]

{/foot;fu}

Abstract

Achilefu S, Dorshow RB, Bugaj JE, Rajagopalan R. Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging. Invest Radiol 2000;35:479–485.

RATIONALE AND OBJECTIVES.

To evaluate the efficacy of a novel tumor receptor-specific small-peptide–near-infrared dye conjugate for tumor detection by optical imaging.

METHODS.

A novel, near-infrared dye-peptide conjugate was synthesized and evaluated for tumor-targeting efficacy in a well-characterized rat tumor model (CA20948) known to express receptors for the chosen peptide. A simple continuous-wave optical imaging system, consisting of a near-infrared laser diode, a cooled CCD camera, and an interference filter, was used in this study.

RESULTS.

Tumor retention of two non–tumor-specific dyes, indocyanine green and its derivatized analogue, bis-propanoic acid cyanine dye (cypate), was negligible. In contrast, the receptor-specific peptide-cypate conjugate (cytate) was retained in the CA20948 tumor, with an excellent tumor-to-normal-tissue ratio in the six rats examined.

CONCLUSIONS.

Optical detection of tumors with a receptor-targeted fluorescent contrast agent has been demonstrated. This result represents a new direction in cancer diagnosis and patient management.