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Molecular Imaging: Exploring the Next Frontier¹

¹ From the Center for the Molecular Imaging Research, Massachusetts General Hospital, 149 13th St, Charlestown, MA 02129. Received January 22, 1999; revision requested March 16; revision received March 18; accepted March 23. Supported in part by National Institutes of Health grants RO1CA54886, RO1NS35258, ROCA174424, and RO1CA59649. Address reprint requests to the author (e-mail: weissleder@helix.mgh.harvard.edu).

View larger version (17K): [in a new window]   Figure 1. Diagrams show mechanisms for molecular imaging at the organ, tissue, cellular, and genetic levels.

View larger version (20K): [in a new window]   Figure 2. Diagrams show comparison of key elements for in vitro and in vivo molecular imaging.

View larger version (101K): [in a new window]   Figure 3. Three-dimensional T1-weighted gradient-echo MR imaging reconstruction (repetition time, 150 msec; echo time, 3.6 msec; flip angle, 34°; voxel size, 39 x 39 x 78 µm) shows tracking of immune cells with magnetically labeled lymphocytes homed to a human glioblastoma tumor (9L tumor model) xenograft in a mouse. Cell were labeled ex vivo by using a magnetic particle with membrane translocation signals (35). Approximately 10,000 cells are distributed throughout the elongated tumor (outlined in red) and cause low MR signal intensity, which is readily detectable. (Imaging was performed in collaboration with Helene Benveniste, MD, PhD, Center for In Vivo Microscopy, Duke Medical Center, Durham, NC.)

View larger version (126K): [in a new window]   Figure 4. Viral gene delivery. Planar scintigraphic image of the whole-body distribution of a genetically engineered herpes simplex virus utilized for gene delivery in a rat. The indium 111-labeled replication-conditioned virus encoding for ß-galactosidase was injected intravenously (150 µCi [5.6 MBq]). Image acquisition time was 5 minutes. Note the predominant viral distribution to liver (white and red areas), which should be useful for gene therapy in this organ (31).

View larger version (100K): [in a new window]   Figure 5. Gene expression. Summed coronal PET image of a rat injected with iodine 124-FIAU, a substrate for viral thymidine kinase. The tracer accumulates in the flank tumor (in vitro-transduced W256-Tk cells) and in the neck tumor (in vivo-transduced W256 tumor). (Reprinted, with permission, from reference 19.)

View larger version (92K): [in a new window]   Figure 6a. Optical imaging of enzyme activity in a human LX1 tumor (2-mm diameter) xenografted into the mammary fat pad of a mouse. (a) Light image. (b) Raw near-infrared image. Note the bright tumor (arrow in b) in the chest. This appearance is due to enzymatic activation of the optically quenched cathepsin imaging probe. (For more information on this type of imaging, see reference 26.)

View larger version (83K): [in a new window]   Figure 6b. Optical imaging of enzyme activity in a human LX1 tumor (2-mm diameter) xenografted into the mammary fat pad of a mouse. (a) Light image. (b) Raw near-infrared image. Note the bright tumor (arrow in b) in the chest. This appearance is due to enzymatic activation of the optically quenched cathepsin imaging probe. (For more information on this type of imaging, see reference 26.)