Visualizing implanted tumors in mice with magnetic resonance imaging using magnetotactic bacteria.
OBJECTIVE
To determine if magnetotactic bacteria can target tumors in mice and provide positive contrast for visualization using magnetic resonance imaging.


METHODS
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.


CONCLUSIONS
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.
Benoit
Michael R
MR
Department of Microbiology and Immunology, Stanford University, Stanford, California 94305-5124, USA.
Mayer
Dirk
D
Barak
Yoram
Y
Chen
Ian Y
IY
Hu
Wei
W
Cheng
Zhen
Z
Wang
Shan X
SX
Spielman
Daniel M
DM
Gambhir
Sanjiv S
SS
Matin
A
A
D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology*; D005260:Female; D052203:Ferrosoferric Oxide / Q000737:chemistry / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D042201:Magnetospirillum / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000382:microbiology; D011859:Radiography; D014183:Transplantation, Heterologous
D052203:Ferrosoferric Oxide