Multi-modality imaging identifies key times for annexin V imaging as an early predictor of therapeutic outcome.

Abstract

Radiolabeled annexin V may provide an early indication of the success or failure of anticancer therapy on a patient-by-patient basis as an in vivo marker of tumor cell killing. An important question that remains is when, after initiation of treatment, should annexin V imaging be performed. To address this issue, we obtained simultaneous in vivo measurements of tumor burden and uptake of radiolabeled annexin V in the syngeneic orthotopic murine BCL1 lymphoma model using in vivo bioluminescence imaging (BLI) and small animal single-photon emission computed tomography (SPECT). BCL1 cells labeled for fluorescence and bioluminescence assays (BCL1-gfp/luc) were injected into mice at a dose that leads to progressive disease within two to three weeks. Tumor response was followed by BLI and SPECT before and after treatment with a single dose of 10 mg/kg doxorubicin. Biodistribution analyses revealed a biphasic increase of annexin V uptake within the tumor-bearing tissues of mice. An early peak occurring before actual tumor cells loss was observed between 1 and 5 hr after treatment, and a second longer sustained rise from 9 to 24 hr after therapy, which heralds the onset of tumor cell loss as confirmed by BLI. Multimodality imaging revealed the temporal patterns of tumor cell loss and annexin V uptake revealing a better understanding of the timing of radiolabeled annexin V uptake for its development as a marker of therapeutic efficacy.

• Authors: Stefanie J Mandl, Carina Mari, Matthias Edinger, Robert S Negrin, Jonathan F Tait, Christopher H Contag, Francis G Blankenberg
• Journal: Molecular imaging (Mol Imaging) Vol. 3 Issue 1 Pg. 1-8 (Jan 2004) ISSN: 1535-3508 [Print] England
• PMID: 15142407 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Annexin A5
• Antibiotics, Antineoplastic
• Luminescent Proteins
• Organotechnetium Compounds
• Radioactive Tracers
• Radiopharmaceuticals
• Green Fluorescent Proteins
• Doxorubicin
• Luciferases

Topics

• Animals
• Annexin A5 (pharmacokinetics)
• Antibiotics, Antineoplastic (toxicity)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Survival
• Doxorubicin (toxicity)
• Female
• Green Fluorescent Proteins
• Injections, Intravenous
• Luciferases (metabolism)
• Luminescent Measurements
• Luminescent Proteins (metabolism)
• Lymphoma, B-Cell (diagnostic imaging, drug therapy, metabolism, pathology)
• Magnetic Resonance Spectroscopy (methods)
• Mice
• Mice, Inbred BALB C
• Neoplasm Transplantation
• Organotechnetium Compounds (pharmacokinetics)
• Radioactive Tracers
• Radiopharmaceuticals
• Retroviridae (genetics)
• Time Factors
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon (methods)
• Treatment Outcome