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Journal of Nuclear Medicine

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OtherBASIC SCIENCE INVESTIGATIONS

Targeting the αvβ3 Integrin for Small-Animal PET/CT of Osteolytic Bone Metastases

Thaddeus J. Wadas, Hongju Deng, Jennifer E. Sprague, Alexander Zheleznyak, Katherine N. Weilbaecher and Carolyn J. Anderson
Journal of Nuclear Medicine November 2009, 50 (11) 1873-1880; DOI: https://doi.org/10.2967/jnumed.109.067140
Thaddeus J. Wadas
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Hongju Deng
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Jennifer E. Sprague
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Alexander Zheleznyak
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Katherine N. Weilbaecher
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Carolyn J. Anderson
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  • FIGURE 1. 
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    FIGURE 1. 

    (A) Structure of CB-TE2A-c(RGDyK). (B) Isosurface image rendered from high-resolution CT data collected on Tax+ and WT mice. Isosurface images are rendered using same parameters and are equivalent. Arrows depict sites of osteolytic bone destruction in spinal vertebrae and femur of Tax+ mouse.

  • FIGURE 2. 
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    FIGURE 2. 

    Biodistribution of 64Cu-RGD is different in Tax+ and WT mice. (A) Statistically significant differences are observed between accumulation of radioactivity in tails of 6- to 12-mo-old Tax+ (n = 12) and WT mice (n = 15). Additionally, uptake of 64Cu-RGD in 6- to 12-mo-old Tax+ mice is higher than in those older than 12 mo (P = 0.003). (B) However, statistically significant differences are not observed when radiopharmaceutical accumulation in tails of Tax+ mice that are older than 12 mo (n = 5) is compared with radiopharmaceutical accumulation in tails of WT mice in same age range (n = 6). (C) Positive correlation exists between accumulated tracer uptake in Tax+ mouse tails and measured serum TRAP levels in blood of these mice. High degree of variability reflects spontaneous nature of animal model. (D) Conversely, no correlation exists between accumulated tracer uptake in WT mouse tails and measured serum TRAP levels in blood of WT mice. Sera from both age groups were combined in parts C and D.

  • FIGURE 3. 
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    FIGURE 3. 

    (A) Coregistered small-animal PET/CT image of Tax+ mouse tail that was imaged with 64Cu-RGD at 1 h after injection. Coronal slice presented here has numerous areas of focal uptake in tail vertebrae. (B) Graphic representation of observed differences in SUV between Tax+ (n = 5) and WT (n = 4) mice. On basis of SUV analysis, more activity is observed in Tax+ mouse tails.

  • FIGURE 4. 
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    FIGURE 4. 

    (A) Coregistered small-animal PET/CT images of Tax+ and WT mice (both 14 mo old) at 1 h after injection. OSEM reconstructions were used here, and only lower body of each mouse was placed in field of view. (A, left image) Sagittal slice of Tax+ mouse tail, which was held in place such that tail looped up onto ventral side of mouse. White brackets indicate where histologic sectioning was conducted. (A, right image) Coregistered small-animal PET/CT image (coronal slice) of WT mouse. Little activity is observed in tail vertebrae of this mouse. (B, left image) TRAP-stained section from tail of Tax+ mouse shown in A, which depicts osteolytic lesion. Several osteoclasts are indicated by black arrows, whereas tumor and proinflammatory cell infiltration is indicated by white arrows. (B, right image) TRAP-stained section from tail of WT mouse. Osteoclasts and proinflammatory cells are not observed in healthy marrow. B = bladder; F = fiducial marker; K = kidney; L = liver.

  • FIGURE 5. 
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    FIGURE 5. 

    Small-animal PET/CT (with 64Cu-RGD) results before (left) and after (right) treatment with ZA. Three animals were used in this proof-of-principle study. Small-animal CT and small-animal PET data were rendered as whole-body reprojected images, which were summations of individual data slices. Notably, changes in bone due to administered therapy are observed in small-animal PET before being observed in the small-animal CT and can be quantified by determining SUVs before and after therapy. (A) Tax+ mouse tail demonstrates appreciable radiopharmaceutical uptake at time of imaging. SUV for whole tail of this animal before treatment was 0.47, but after therapy it was 0.13. (B) Different Tax+ mouse tail has developed large soft-tissue tumor. Here SUV analysis was conducted on 2 vertebrae separated by tumor. Before therapy, proximal vertebra (PV) and distal vertebra (DV) had SUVs of 0.38 and 0.43, respectively. After treatment with ZA, SUV of PV was 0.12 and SUV of DV was 0.12. F = fiducial marker; T = tumor.

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Journal of Nuclear Medicine: 50 (11)
Journal of Nuclear Medicine
Vol. 50, Issue 11
November 2009
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Targeting the αvβ3 Integrin for Small-Animal PET/CT of Osteolytic Bone Metastases
Thaddeus J. Wadas, Hongju Deng, Jennifer E. Sprague, Alexander Zheleznyak, Katherine N. Weilbaecher, Carolyn J. Anderson
Journal of Nuclear Medicine Nov 2009, 50 (11) 1873-1880; DOI: 10.2967/jnumed.109.067140

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Targeting the αvβ3 Integrin for Small-Animal PET/CT of Osteolytic Bone Metastases
Thaddeus J. Wadas, Hongju Deng, Jennifer E. Sprague, Alexander Zheleznyak, Katherine N. Weilbaecher, Carolyn J. Anderson
Journal of Nuclear Medicine Nov 2009, 50 (11) 1873-1880; DOI: 10.2967/jnumed.109.067140
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