Preclinical evaluation of a 68Ga-labeled biotin analogue for applications in islet transplantation

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Eriksson, OlofUppsala universitet,Plattformen för preklinisk PET (author)

Preclinical evaluation of a 68Ga-labeled biotin analogue for applications in islet transplantation

Article/chapterEnglish2012

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Elsevier BV,2012
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LIBRIS-ID:oai:DiVA.org:uu-169440
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-169440URI
https://doi.org/10.1016/j.nucmedbio.2011.09.009DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:124313138URI

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Language:English
Summary in:English

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INTRODUCTION:Islet transplantation is a promising treatment for type 1 diabetes mellitus, but the fate of the cells after intraportal infusion is unclear. It is therefore imperative to develop novel techniques for noninvasive imaging and quantification of events following islet transplantation.METHODS:Small islet-like microbeads, avidin-covered agarose resins (AARs), were used as a model system for islet transplantation. Capability for specific [(68)Ga]Ga-DOTA-(PEG)(2)-biotin uptake and retention for either AARs or human islets conjugated with avidin by means of a heparin scaffold was studied in vitro. Biodistribution of the novel positron emission tomography (PET) tracer [(68)Ga]Ga-DOTA-(PEG)(2)-biotin was evaluated in mice treated by intraportal transplantation of AARs by μPET/computed tomography and ex vivo organ distribution and compared with control mice.RESULTS:AARs had high capability to bind [(68)Ga]Ga-DOTA-(PEG)(2)-biotin, close to 50% of administrated tracer/μl in vitro (>0.25 MBq/μl). Avidin-tagged human islets could bind on average 2.2% of administered tracer/μl. Specificity (>90%) and retention (>90% after 1 h) were high for both AARs and avidin-tagged islets. Hepatic tracer uptake and retention were increased in mice transplanted with AARs [standardized uptake value (SUV)=2.6] compared to the untreated group (SUV=1.4). In vivo uptake of tracer to AARs was blocked by preadministration of unlabeled biotin.CONCLUSIONS:Avidin-tagged islet-like objects can be tracked in hepatic volume after intraportal transplantation by using [(68)Ga]Ga-DOTA-(PEG)(2)-biotin and PET.

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Carlsson, FredrikUppsala universitet,Klinisk immunologi(Swepub:uu)frcar179 (author)
Blom, ElisabethUppsala universitet,Fysikalisk-organisk kemi (author)
Sundin, AndersKarolinska Institutet,Uppsala universitet,Enheten för radiologi(Swepub:uu)anderssu (author)
Långström, BengtUppsala universitet,Fysikalisk-organisk kemi(Swepub:uu)benglang (author)
Korsgren, OlleUppsala universitet,Klinisk immunologi(Swepub:uu)ollekors (author)
Velikyan, IrinaUppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Enheten för radiologi(Swepub:uu)irinveli (author)
Uppsala universitetPlattformen för preklinisk PET (creator_code:org_t)

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In:Nuclear Medicine and Biology: Elsevier BV39:3, s. 415-4210969-80511872-9614

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Other Basic Medi ...

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By the university: Uppsala University; Karolinska Institutet

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