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Small-Animal SPECT and SPECT/CT: Important Tools for Preclinical Investigation^*

Benjamin L. Franc¹, Paul D. Acton², Carina Mari^1,3 and Bruce H. Hasegawa^,1

¹ Department of Radiology, Center for Molecular and Functional Imaging, University of California, San Francisco, San Francisco, California; ² Johnson & Johnson Pharmaceutical Research and Development, Spring House, Pennsylvania, and Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania; and ³ Department of Radiology, Department of Veteran's Affairs Medical Center, San Francisco, California

View larger version (96K): [in this window] [in a new window]   FIGURE 1.  Coregistered in vivo micro-SPECT/CT images of 201Tl to assess myocardial perfusion and 99mTc-NC100692 targeted at vβ3 integrin to identify angiogenesis in wild-type and matrix metalloproteinase 9 (MMP-9) null mice. 99mTc-NC100692 micro-SPECT images (red) are fused with 201Tl (green) and CT (gray) images to define uptake of vβ3-targeted radiotracer relative to 201Tl perfusion defect and anatomic structures within chest (CT performed with both 99mTc and 201Tl data provides template for fusion). Boxed areas on left are magnified on right. Increased 99mTc-NC100692 uptake is seen in anterior-lateral infarct territory (arrows) and 99mTc-NC100692 activity associated with angiogenesis at thoracotomy site (*), demonstrating importance of simply knowing location of sternum as indicated on CT. 99mTc-NC100692 uptake also was noted in liver. (Reprinted with permission of (117).)

View larger version (18K): [in this window] [in a new window]   FIGURE 2.  (A) Early small-animal SPECT systems were developed using single scintillation camera with single-pinhole collimator. (B) Modern small-animal SPECT systems use multiple detectors, each with multipinhole collimators. (C) Schematic of pinhole collimator geometry and relationships between object, its FOV, and its image on plane of detector. Angle between collimator walls (), linear attenuation coefficient of collimator material (y), and pinhole diameter must be known to derive effective pinhole diameter (de). Geometric resolution measured on detector plane (Rc) is function of de, pinhole aperture-to-object distance (b), and pinhole aperture-to-detector distance (t). In figure, y equals radius of reconstruction circle and Ro equals detector point-spread function projected to object plane (spatial resolution in object plane at distance b from pinhole aperture). More detailed discussion of these relationships may be found in the references authored by Cherry et al., Metzler et al., and Metzler et al. (118–120). (D) Object is magnified by factor b/t onto plane of detector effective resolution can be improved by pinhole magnification.

View larger version (39K): [in this window] [in a new window]   FIGURE 3.  Coronal (A) and transverse (B) SPECT images showing uptake of DAT imaging agent 99mTc-[2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)] (TRODAT-1) in mouse brain 1 h after injection. Generally, greater localization of TRODAT-1 is seen in striatum than in cortical structures. (C) In vivo measurement of striatum-to-cerebellum ratio with SPECT, using kinetic modeling with extraction of input function from cerebellum (Ref region) and from relative striatum-to-cerebellum concentrations at equilibrium (Ratio), showed correlations of R2 = 0.92 (P = 0.04) and R2 = 0.999 (P < 0.01), vs. ex vivo measurements. (Reprinted with permission of (48).)

View larger version (22K): [in this window] [in a new window]   FIGURE 4.  Cardiac long- and short-axis SPECT images of normal (A and C) and infarcted (E and G) heart using perfusion tracer 99mTc-sestamibi (MIBI). Signal from 111In-labeled stem cells (In, color) was overlaid on gray-scale MIBI images for normal (B and D) and infarcted (F and H) heart.

View larger version (40K): [in this window] [in a new window]   FIGURE 5.  Small-animal SPECT/CT in oncology research. Coronal (A–E [top], F) and transaxial (A–E [bottom]) images from SPECT/CT study of LNCaP prostate cancer xenograft model 72 h after administration of antibody to PSMA labeled with 177Lu. Tumor uptake is difficult to localize on SPECT images (A) but is easily localized anatomically on SPECT/CT overlay images (B). To quantify uptake of radiopharmaceutical, borders of tumor may be visualized on CT (C). Region of interest is selected on basis of CT (D) and applied to SPECT data (E). Three-dimensional renderings (F; arrow indicates tumor) may be helpful in better understanding anatomic relationships but rarely play role in quantification.

View larger version (17K): [in this window] [in a new window]   FIGURE 6.  (A) Schematic of nonoverlapping multipinhole system. Object FOV is projected on detector surface through (in this case) 3 pinholes without overlap. Multipinhole design increases system sensitivity roughly by factor equal to number of pinholes. (B) Schematic of overlapping (multiplexed) multipinhole system. Object FOV is projected on detector surface through (in this case) 7 pinholes. In contrast to system in A, there is significant overlap of projections on detector surface in B.