Document Detail


Human islet cell MORF/cMORF pretargeting in a xenogeneic murine transplant model.
MedLine Citation:
PMID:  21361360     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Noninvasive measurement of human islet cell mass in pancreas or following islet transplantation by nuclear imaging has yet to be achieved. It has been shown using mouse tumor models that pretargeting imaging strategies are sensitive and can greatly increase target to nontarget signal ratios. The objective now is to demonstrate the specific pretargeting of human islet cells in mice. Our pretargeting strategy uses an anti-human islet cell antibody HPi1, conjugated to a phosphorodiamidate morpholino oligomer (MORF) that binds specifically to a (99m)Tc labeled complementary MORF (cMORF). Sensitivity and specificity of the pretargeting were first validated in culture using a human beta cell line (betalox5) and a negative control human cell line (HEK293). Pretargeting was then used to target and visualize these two cell lines and human islets transplanted subcutaneously in NOD-scid IL2rγ(null) mice. In culture, (99m)Tc accumulation on the betalox5 cells pretargeted by MORF-HPi1 was 100-fold higher than on untreated betalox5 cells or following treatment with native HPi1 and much higher than on the MORF-HPi1 pretargeted control HEK293 cells. Small animal imaging readily localized the transplanted betalox5 cells and human islets, but not the HEK293 cells. Ex vivo counting demonstrated 3-fold higher (99m)Tc accumulation in the transplanted betalox5 cells and human islets than in the control HEK293 cells. The target accumulation was also shown to increase linearly with increased numbers of the implanted betalox5 cells. These results demonstrate specific binding of radioactivity and successful imaging of human betalox5 cells and human islets transplanted in mice. Thus MORF/cMORF pretargeting may be useful to measure noninvasively human islet cell mass within the pancreas or following islet transplantation.
Authors:
Guozheng Liu; Shuping Dou; Dengfeng Cheng; Jean Leif; Mary Rusckowski; Philip R Streeter; Leonard D Shultz; Donald J Hnatowich; Dale L Greiner
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-04-21
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  8     ISSN:  1543-8392     ISO Abbreviation:  Mol. Pharm.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-06     Completed Date:  2011-09-23     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  767-73     Citation Subset:  IM    
Affiliation:
Department of Radiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. guozheng.liu@umassmed.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies / metabolism*
Chromatography, High Pressure Liquid
HEK293 Cells
Humans
Insulin-Secreting Cells / cytology*,  metabolism*,  transplantation*
Mice
Mice, Inbred NOD
Mice, SCID
Morpholines / metabolism*
Morpholinos
Grant Support
ID/Acronym/Agency:
AI050864/AI/NIAID NIH HHS; AI46629/AI/NIAID NIH HHS; CA94994/CA/NCI NIH HHS; DK082894/DK/NIDDK NIH HHS; DK089572/DK/NIDDK NIH HHS; DK32520/DK/NIDDK NIH HHS; DK72473/DK/NIDDK NIH HHS; P01 AI046629-11/AI/NIAID NIH HHS; R01 CA094994-09/CA/NCI NIH HHS; R21 DK082894-02/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies; 0/Morpholines; 0/Morpholinos
Comments/Corrections

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