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OtherBASIC SCIENCE INVESTIGATIONS

Use of a Novel Arg-Gly-Asp Radioligand, 18F-AH111585, to Determine Changes in Tumor Vascularity After Antitumor Therapy

Matthew S. Morrison, Sally-Ann Ricketts, Jon Barnett, Alan Cuthbertson, Jean Tessier and Stephen R. Wedge
Journal of Nuclear Medicine January 2009, 50 (1) 116-122; DOI: https://doi.org/10.2967/jnumed.108.056077
Matthew S. Morrison
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Sally-Ann Ricketts
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Jon Barnett
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Alan Cuthbertson
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Jean Tessier
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Stephen R. Wedge
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  • FIGURE 1. 
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    FIGURE 1. 

    (A) Biodistribution and clearance profile of 18F-AH111585. (B) Key tumor–to–background-tissue ratios of 18F-AH111585; values are expressed as ratio of tumor %ID/g to background tissue %ID/g. (C) Excretion profile of 18F-AH111585 in mouse LLC model up to 240 min after injection. Values are expressed as %ID/g or %ID and presented as mean (±SD) of 5 experiments (n = 6).

  • FIGURE 2. 
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    FIGURE 2. 

    Inhibition of 18F-AH111585 uptake by low-dose paclitaxel (5 and 10 mg/kg) therapy in the mouse LLC model (120 min after injection of 18F-AH111585, day 15 after LLC cell inoculation). At the same paclitaxel dose level, no effect was observed on 14C-FDG uptake. Values are expressed in %ID/g and presented as mean (±SD) of 2 experiments (n = 4). *P < 0.05, compared with the corresponding control group.

  • FIGURE 3. 
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    FIGURE 3. 

    (A) Inhibition of 18F-AH111585 uptake in Calu-6 tumors in nude mice before and after treatment with 3 doses of ZD4190 (100 mg/kg) or vehicle control. Values are expressed in %ID/g and presented as individual data. (B) Summarized data demonstrate percentage change in uptake of 18F-AH111585 in Calu-6–tumored CD-1 nude mice before and after treatment with 3 doses of ZD4190 (100 mg/kg) or vehicle control. Data are presented for individual animals. *P < 0.01, compared with vehicle control group.

  • FIGURE 4. 
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    FIGURE 4. 

    Representative coregistered small-animal PET and micro-CT images demonstrating 18F-AH111585 uptake at 120 min in Calu-6 xenograft model before (A) and after (B) administration of 3 doses of vehicle control or before (C) and after (D) 3 doses of ZD4190 (100 mg/kg). Contrast is clearly seen in Calu-6 tumors located on left shoulder region in both ZD4190-treated and vehicle control animals. The only additional higher activity concentration was found in bladder. In addition, 22Na fiducial markers can be seen located on base of imaging bed (used for PET/CT coregistration). ROI analysis for tumor uptake before ZD4190 therapy was 1.7 %ID/g, decreasing to 1.1 %ID/g after ZD4190 therapy. Muscle uptake was maintained at 0.5 %ID/g in pre- and post-ZD4190–therapy images. For animals treated with vehicle control alone, ROI analysis for tumor uptake before vehicle control was 2.1 %ID/g, increasing to 2.5 %ID/g after therapy. Muscle uptake was maintained at 0.3 %ID/g in pre- and posttherapy images.

Tables

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    TABLE 1

    Biodistribution of 18F-AH111585 in Mouse LLC Model

    Time (min after injection)Biodistribution (%ID/g)
    BloodMuscleLungLiverTumor
    56.35 (2.34)1.78 (0.57)6.54 (1.71)6.01 (1.03)2.69 (0.53)
    106.56 (1.92)1.66 (0.14)8.20 (1.71)5.43 (1.05)3.11 (0.68)
    301.81 (0.53)1.03 (0.34)3.90 (1.41)2.57 (0.69)2.68 (0.47)
    600.84 (0.39)0.56 (0.23)2.12 (0.90)1.48 (0.65)1.84 (0.45)
    1200.45 (0.13)0.27 (0.07)1.17 (0.28)0.89 (0.29)1.49 (0.32)
    2400.07 (0.02)0.05 (0.01)0.27 (0.09)0.17 (0.02)0.40 (0.05)
    • Data are mean ± SD of %ID/g; n = 6 per time point.

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Journal of Nuclear Medicine: 50 (1)
Journal of Nuclear Medicine
Vol. 50, Issue 1
January 2009
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Use of a Novel Arg-Gly-Asp Radioligand, 18F-AH111585, to Determine Changes in Tumor Vascularity After Antitumor Therapy
Matthew S. Morrison, Sally-Ann Ricketts, Jon Barnett, Alan Cuthbertson, Jean Tessier, Stephen R. Wedge
Journal of Nuclear Medicine Jan 2009, 50 (1) 116-122; DOI: 10.2967/jnumed.108.056077

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Use of a Novel Arg-Gly-Asp Radioligand, 18F-AH111585, to Determine Changes in Tumor Vascularity After Antitumor Therapy
Matthew S. Morrison, Sally-Ann Ricketts, Jon Barnett, Alan Cuthbertson, Jean Tessier, Stephen R. Wedge
Journal of Nuclear Medicine Jan 2009, 50 (1) 116-122; DOI: 10.2967/jnumed.108.056077
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