title: The synthesis, magnetic purification and evaluation of 99mTc-labeled microbubbles.
abstract: BACKGROUND
  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 (99m)Tc. 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 (99m)Tc-labeled biotin derivative ((99m)TcL1) was prepared and incubated with streptavidin-coated MBs. The (99m)Tc-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 (99m)Tc-labeled bubbles in healthy C57Bl-6 mice.
  
  
  RESULTS
  The imaging and biodistribution data showed rapid accumulation and retention of (99m)Tc-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, (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).
  
  
  CONCLUSIONS
  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.
authors: Centre for Probe Development and Commercialization, Hamilton, Ontario, Canada.
authors: Neva
authors: N
authors: Lazarova
authors: Patrick W
authors: PW
authors: Causey
authors: Jennifer A
authors: JA
authors: Lemon
authors: Shannon K
authors: SK
authors: Czorny
authors: John R
authors: JR
authors: Forbes
authors: Aimen
authors: A
authors: Zlitni
authors: Afaf
authors: A
authors: Genady
authors: F Stuart
authors: FS
authors: Foster
authors: John F
authors: JF
authors: Valliant
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D005260:Female; D007421:Intestine, Small / Q000000981:diagnostic imaging / Q000378:metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D045423:Microbubbles; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D013154:Spleen / Q000000981:diagnostic imaging / Q000378:metabolism; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D001743:Urinary Bladder / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: D003287:Contrast Media; D015609:Organotechnetium Compounds