The synthesis, magnetic purification and evaluation of 99mTc-labeled microbubbles
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...
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Veröffentlicht in: | Nuclear medicine and biology 2011-11, Vol.38 (8), p.1111-1118 |
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Zusammenfassung: | 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.
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.
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).
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. |
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ISSN: | 0969-8051 1872-9614 |
DOI: | 10.1016/j.nucmedbio.2011.04.008 |