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Visualizing implanted tumors in mice with magnetic resonance imaging using magnetotactic bacteria.

TitleVisualizing implanted tumors in mice with magnetic resonance imaging using magnetotactic bacteria.
Publication TypeJournal Article
Year of Publication2009
AuthorsBenoit MR, Mayer D, Barak Y, Chen IY, Hu W, Cheng Z, Wang SX, Spielman DM, Gambhir SS, Matin A
JournalClin Cancer Res
Volume15
Issue16
Pagination5170-7
Date Published2009 Aug 15
ISSN1078-0432
KeywordsAnimals, Bacterial Adhesion, Cells, Cultured, Chemotaxis, Female, Ferrosoferric Oxide, Magnetic Resonance Imaging, Magnetospirillum, Mice, Mice, Nude, Neoplasm Transplantation, Neoplasms, Transplantation, Heterologous
Abstract

PURPOSE: To determine if magnetotactic bacteria can target tumors in mice and provide positive contrast for visualization using magnetic resonance imaging.

EXPERIMENTAL DESIGN: The ability of the magnetotactic bacterium, Magnetospirillum magneticum AMB-1 (referred to from here as AMB-1), to confer positive magnetic resonance imaging contrast was determined in vitro and in vivo. For the latter studies, AMB-1 were injected either i.t. or i.v. Bacterial growth conditions were manipulated to produce small (approximately 25-nm diameter) magnetite particles, which were observed using transmission electron microscopy. Tumor targeting was confirmed using 64Cu-labeled bacteria and positron emission tomography and by determination of viable cell counts recovered from different organs and the tumor.

RESULTS: We show that AMB-1 bacteria with small magnetite particles generate T1-weighted positive contrast, enhancing in vivo visualization by magnetic resonance imaging. Following i.v. injection of 64Cu-labeled AMB-1, positron emission tomography imaging revealed increasing colonization of tumors and decreasing infection of organs after 4 hours. Viable cell counts showed that, by day 6, the bacteria had colonized tumors but were cleared completely from other organs. Magnetic resonance imaging showed a 1.22-fold (P = 0.003) increased positive contrast in tumors on day 2 and a 1.39-fold increase (P = 0.0007) on day 6.

CONCLUSION: Magnetotactic bacteria can produce positive magnetic resonance imaging contrast and colonize mouse tumor xenografts, providing a potential tool for improved magnetic resonance imaging visualization in preclinical and translational studies to track cancer.

DOI10.1158/1078-0432.CCR-08-3206
Alternate JournalClin. Cancer Res.
PubMed ID19671860
PubMed Central IDPMC3409839
Grant ListF32GM077827 / GM / NIGMS NIH HHS / United States
P50 CA114747 / CA / NCI NIH HHS / United States
P50 CA114747 / CA / NCI NIH HHS / United States
R01 CA125074 / CA / NCI NIH HHS / United States
R01 CA125074-01A1 / CA / NCI NIH HHS / United States
RR09784 / RR / NCRR NIH HHS / United States
T32-AI07328 / AI / NIAID NIH HHS / United States