microPET-Based Biodistribution of Quantum Dots in Living Mice

This study evaluates the quantitative biodistribution of commercially available CdSe quantum dots (QD) in mice. Methods: 64Cu-Labeled 800- or 525-nm emission wavelength QD (21- or 12-nm diameter), with or without 2,000 MW (molecular weight) polyethylene glycol (PEG), were injected intravenously into mice (5.55 MBq/25 pmol QD) and studied using well counting or by serial microPET and region-of-interest analysis. Results: Both methods show rapid uptake by the liver (27.4–38.9 %ID/g) (%ID/g is percentage injected dose per gram tissue) and spleen (8.0–12.4 %ID/g). Size has no influence on biodistribution within the range tested here. Pegylated QD have slightly slower uptake into liver and spleen (6 vs. 2 min) and show additional low-level bone uptake (6.5–6.9 %ID/g). No evidence of clearance from these organs was observed. Conclusion: Rapid reticuloendothelial system clearance of QD will require modification of QD for optimal utility in imaging living subjects. Formal quantitative biodistribution/imaging studies will be helpful in studying many types of nanoparticles, including quantum dots.

[1]  M S Patterson,et al.  Quantification of bioluminescence images of point source objects using diffusion theory models , 2006, Physics in medicine and biology.

[2]  Laura A Lavery,et al.  Labeling tumor cells with fluorescent nanocrystal-aptamer bioconjugates. , 2006, Biosensors & bioelectronics.

[3]  Charles Nicholson,et al.  In vivo diffusion analysis with quantum dots and dextrans predicts the width of brain extracellular space. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Sanjiv S Gambhir,et al.  Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects. , 2006, Nano letters.

[5]  John V Frangioni,et al.  Size series of small indium arsenide-zinc selenide core-shell nanocrystals and their application to in vivo imaging. , 2006, Journal of the American Chemical Society.

[6]  Sanjiv S Gambhir,et al.  Self-illuminating quantum dot conjugates for in vivo imaging , 2006, Nature Biotechnology.

[7]  L. Cohn,et al.  Sentinel Lymph Node Mapping of the Gastrointestinal Tract by Using Invisible Light , 2006, Annals of Surgical Oncology.

[8]  Nicholas A Peppas,et al.  Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. , 2006, International journal of pharmaceutics.

[9]  Jinha M. Park,et al.  Reproducibility of 3'-deoxy-3'-(18)F-fluorothymidine microPET studies in tumor xenografts in mice. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[10]  Paras N Prasad,et al.  Folate-receptor-mediated delivery of InP quantum dots for bioimaging using confocal and two-photon microscopy. , 2005, Journal of the American Chemical Society.

[11]  Vladimir P Torchilin,et al.  Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo , 2005, Nature Medicine.

[12]  L. Cohn,et al.  Intraoperative identification of esophageal sentinel lymph nodes with near-infrared fluorescence imaging. , 2005, The Journal of thoracic and cardiovascular surgery.

[13]  F. Marshall,et al.  In vivo molecular and cellular imaging with quantum dots. , 2005, Current opinion in biotechnology.

[14]  S. Gambhir,et al.  Quantum Dots for Live Cells, in Vivo Imaging, and Diagnostics , 2005, Science.

[15]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[16]  Byron Ballou,et al.  Noninvasive imaging of quantum dots in mice. , 2004, Bioconjugate chemistry.

[17]  J Szebeni,et al.  Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. , 2003, Progress in lipid research.

[18]  Sanjiv Sam Gambhir,et al.  AMIDE: a free software tool for multimodality medical image analysis. , 2003, Molecular imaging.

[19]  R. N. Goble,et al.  Performance evaluation of the microPET R4 PET scanner for rodents , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[20]  Erkki Ruoslahti,et al.  Nanocrystal targeting in vivo , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[21]  M. Bally,et al.  Controlling the Physical Behavior and Biological Performance of Liposome Formulations Through Use of Surface Grafted Poly(ethylene Glycol) , 2002, Bioscience reports.

[22]  W. Oyen,et al.  Factors affecting the accelerated blood clearance of polyethylene glycol-liposomes upon repeated injection. , 2001, The Journal of pharmacology and experimental therapeutics.

[23]  O. Boerman,et al.  In vivo applications of PEG liposomes: unexpected observations. , 2001, Critical reviews in therapeutic drug carrier systems.

[24]  W. Oyen,et al.  Preclinical and clinical evidence for disappearance of long-circulating characteristics of polyethylene glycol liposomes at low lipid dose. , 2000, The Journal of pharmacology and experimental therapeutics.