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Journal of Nuclear Medicine

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Meeting ReportPoster Presentations - Physicians/Scientists/Pharmacists

Evaluation of peptide-mediated targeting phage as a potential beta-cell imaging agent

Mai Lin, Michael McGuire, Serguei Seliounine, Edward Tsyganov, Dean Sherry, Kathlynn Brown and Xiankai Sun
Journal of Nuclear Medicine May 2006, 47 (suppl 1) 519P;
Mai Lin
1Radiology, UT Southwestern Medical Center at Dallas, Dallas, Texas
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Michael McGuire
3Internal Medicine, UT Southwestern Medical Center at Dallas, Dallas, Texas
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Serguei Seliounine
1Radiology, UT Southwestern Medical Center at Dallas, Dallas, Texas
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Edward Tsyganov
1Radiology, UT Southwestern Medical Center at Dallas, Dallas, Texas
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Dean Sherry
2Advanced Imging Research Center, UT Southwestern Medical Center at Dallas, Dallas, Texas
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Kathlynn Brown
3Internal Medicine, UT Southwestern Medical Center at Dallas, Dallas, Texas
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Xiankai Sun
1Radiology, UT Southwestern Medical Center at Dallas, Dallas, Texas
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Abstract

1890

Objectives: Non-invasive assessment of β-cell mass in pancreas is a challenge for any imaging modality due to the fact that the islets of Langerhans contribute only 2-3% of the adult pancreas. To date, there have been few reports on imaging of β-cell mass. Recently, a rat islet peptide (RIP) phage clone, which recognizes the islets of Langerhans in normal rats, has been reported (Samli et al. Diabetes 2005, 54:2103). To explore the potential of this phage as a nuclear imaging agent for β-cell evaluation, we radiolabled it with 124/125I and performed biodistribution and PET imaging studies in normal Sprague-Dawley rats.

Methods: Two phage clones (the RIP phage and a random control) were radiolabeled with 124/125I and purified by centricon YM-30 filters. In biodistribution, 5 X 107 plaque-forming units (pfu) of 125I labeled phage clones (5 μCi) was injected via the tail-vein. The animals (n = 4) were sacrificed at 1 h, 4 h, 24 h, and 48 h postinjection (p.i.), and organs of interest were removed and counted to assess the RIP phage targeting specificity as compared to the control. Small animal PET imaging was performed with 124I labeled phage clones (1 X 109 pfu; 270-330 μCi).

Results: High radiochemical purity (> 95%) was obtained for the radiolabeling of both phage clones as determined by radio-TLC. The highest achievable specific activity was 5 X 10-5 μCi/pfu. The RIP phage showed significantly higher pancreas uptake than the control at 4 h p.i. (RIP phage: 0.35 ± 0.08 %ID/g; Control: 0.17 ± 0.05 %ID/g. p < 0.01) indicative of specific RIP phage targeting. Both phage clones also showed high uptake in lungs, liver, and spleen but clearance from these tissues was rapid (>75 %ID excreted within 24 h p.i.). As shown in the PET images, the RIP phage preferentially accumulated in the liver-stomach region. The bright area between the stomach and the liver probably reflects the RIP phage accumulation in pancreas or spleen. Elevated pancreas uptake of the RIP phage, compared to muscle and liver, was further confirmed by post-PET biodistribution. In contrast, the control did not show significant pancreas accumulation. Further imaging studies are under way to verify this observation.

Conclusions: The preliminary results showed the potential application of RIP peptide mediated phage clones to PET imaging of β cells.


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Comparative Biodistribution Data of I-125 Labeled Phages in Healthy SD Rats Post 4 h Injection

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Journal of Nuclear Medicine
Vol. 47, Issue suppl 1
May 1, 2006
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Evaluation of peptide-mediated targeting phage as a potential beta-cell imaging agent
Mai Lin, Michael McGuire, Serguei Seliounine, Edward Tsyganov, Dean Sherry, Kathlynn Brown, Xiankai Sun
Journal of Nuclear Medicine May 2006, 47 (suppl 1) 519P;

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Evaluation of peptide-mediated targeting phage as a potential beta-cell imaging agent
Mai Lin, Michael McGuire, Serguei Seliounine, Edward Tsyganov, Dean Sherry, Kathlynn Brown, Xiankai Sun
Journal of Nuclear Medicine May 2006, 47 (suppl 1) 519P;
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