Journal
NUCLEAR MEDICINE AND BIOLOGY
Volume 38, Issue 8, Pages 1111-1118Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.nucmedbio.2011.04.008
Keywords
Microbubbles; Ultrasound; Tc-99m; SPECT
Funding
- Ontario Institute for Cancer Research (OICR) through Government of Ontario
- Ontario Research Fund
- Canadian Institutes of Health Research
- Terry Fox Foundation
- Biotage Inc.
- VisualSonics Inc.
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Introduction: Ultrasound (US) contrast agents based on micrbbubbles (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 Tc-99m. 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 Tc-99m-labeled biotin derivative ((99m)TcL1) was prepared and incubated with streptavidin-coated MBs. The Tc-99m-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 (99m)TcL1 and Tc-99m-labeled bubbles in healthy C57B1-6 mice. Results: The imaging and biodistribution data showed rapid accumulation and retention of Tc-99m-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 %1D/g at 60 min). In contrast, (99m)TcL1 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. (C) 2011 Published by Elsevier Inc.
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