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Lazarova N.,Center for Probe Development and Commercialization | Causey P.W.,Center for Probe Development and Commercialization | Lemon J.A.,Center for Probe Development and Commercialization | Czorny S.K.,McMaster University | And 6 more authors.
Nuclear Medicine and Biology | Year: 2011

Introduction: Ultrasound (US) contrast agents based on microbubbles (MBs) are being investigated as platforms for drug and gene delivery. A methodology for determining the distribution and fate of modified MBs quantitatively in vivo can be achieved by tagging MBs directly with 99mTc. This creates the opportunity to employ dual-modality imaging using both US and small animal SPECT along with quantitative ex vivo tissue counting to evaluate novel MB constructs. Methods: A 99mTc-labeled biotin derivative ( 99mTcL1) was prepared and incubated with streptavidin-coated MBs. The 99mTc-labeled bubbles were isolated using a streptavidin-coated magnetic-bead purification strategy that did not disrupt the MBs. A small animal scintigraphic/CT imaging study as well as a quantitative biodistribution study was completed using 99mTcL1 and 99mTc-labeled bubbles in healthy C57Bl-6 mice. Results: The imaging and biodistribution data showed rapid accumulation and retention of 99mTc-MBs in the liver (68.2±6.6 %ID/g at 4 min; 93.3±3.2 %ID/g at 60 min) and spleen (214.2±19.7 %ID/g at 4 min; 213.4±19.7 %ID/g at 60 min). In contrast, 99mTcL1 accumulated in multiple organs including the small intestine (22.5±3.6 %ID/g at 4 min; 83.4±5.9 %ID/g at 60 min) and bladder (184.0±88.1 %ID/g at 4 min; 24.2±17.7 %ID/g at 60 min). Conclusion: A convenient means to radiolabel and purify MBs was developed and the distribution of the labeled products determined. The result is a platform which can be used to assess the pharmacokinetics and fate of novel MB constructs both regionally using US and throughout the entire subject in a quantitative manner by employing small animal SPECT and tissue counting. © 2011.

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