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

详细信息    查看全文

• 作者：Olof Eriksson^a ; ^{olof.eriksson@pet.medchem.uu.se} ; Fredrik Carlsson^b ; Elisabeth Blom^c ; Anders Sundin^d ; Bengt Lå ; ngstr&#246 ; m^c ; Olle Korsgren^b ; Irina Velikyan^e
• 关键词：Islet transplantation ; Avidin&ndash ; biotin ; Pretargeting ; Islet imaging
• 刊名：Nuclear Medicine and Biology
• 出版年：2012
• 出版时间：April, 2012
• 年：2012
• 卷：39
• 期：3
• 页码：415-421
• 全文大小：609 K

文摘

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 [⁶⁸Ga]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 [⁶⁸Ga]Ga-DOTA-(PEG)₂-biotin was evaluated in mice treated by intraportal transplantation of AARs by ¦ÌPET/computed tomography and ex vivo organ distribution and compared with control mice.

Results

AARs had high capability to bind [⁶⁸Ga]Ga-DOTA-(PEG)₂-biotin, close to 50 % of administrated tracer/¦Ìl in vitro (>0.25 MBq/¦Ìl). Avidin-tagged human islets could bind on average 2.2 % of administered tracer/¦Ìl. 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 [⁶⁸Ga]Ga-DOTA-(PEG)₂-biotin and PET.