Optical imaging of disseminated leukemia models in mice with near-infrared probe conjugated to a monoclonal antibody.
BACKGROUND
The assessment of anticancer agents to treat leukemia needs to have animal models closer to the human pathology such as implantation in immunodeficient mice of leukemic cells from patient samples. A sensitive and early detection of tumor cells in these orthotopic models is a prerequisite for monitoring engraftment of leukemic cells and their dissemination in mice. Therefore, we developed a fluorescent antibody based strategy to detect leukemic foci in mice bearing patient-derived leukemic cells using fluorescence reflectance imaging (FRI) to determine when to start treatments with novel antitumor agents.


METHODS
Two mAbs against the CD44 human myeloid marker or the CD45 human leukocyte marker were labeled with Alexa Fluor 750 and administered to leukemia-bearing mice after having verified the immunoreactivity in vitro. Bioluminescent leukemic cells (HL60-Luc) were used to compare the colocalization of the fluorescent mAb with these cells. The impact of the labeled antibodies on disease progression was further determined. Finally, the fluorescent hCD45 mAb was tested in mice engrafted with human leukemic cells.


RESULTS
The probe labeling did not modify the immunoreactivity of the mAbs. There was a satisfactory correlation between bioluminescence imaging (BLI) and FRI and low doses of mAb were sufficient to detect leukemic foci. However, anti-hCD44 mAb had a strong impact on the tumor proliferation contrary to anti-hCD45 mAb. The use of anti-hCD45 mAb allowed the detection of leukemic patient cells engrafted onto NOD/SCID mice.


CONCLUSIONS
A mAb labeled with a near infrared fluorochrome is useful to detect leukemic foci in disseminated models provided that its potential impact on tumor proliferation has been thoroughly documented.
Centre de Recherche en Oncologie Expérimentale, Institut de Recherche Pierre Fabre, Toulouse, France. spesnel@cnrs-orleans.fr
Sabrina
S
Pesnel
Arnaud
A
Pillon
Laurent
L
Créancier
Stéphanie
S
Lerondel
Alain
A
Le Pape
Christian
C
Recher
Cécile
C
Demur
Nicolas
N
Guilbaud
Anna
A
Kruczynski
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000378:metabolism*; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007275:Injections, Intravenous; D007938:Leukemia / Q000175:diagnosis* / Q000473:pathology*; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008136:Longevity; D008163:Luminescent Measurements; D051379:Mice; D016513:Mice, SCID; D015203:Reproducibility of Results; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
D000911:Antibodies, Monoclonal; D005456:Fluorescent Dyes; D017493:Leukocyte Common Antigens