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

Mol Imaging. 2004 Jan;3(1):1-8. doi: 10.1162/153535004773861679.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / 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

Substances

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