title: 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.affiliation: Stanford University, School of Medicine, CA 94305-5208, USA.
authors.forename: Stefanie J
authors.initials: SJ
authors.lastname: Mandl
authors.forename: Carina
authors.initials: C
authors.lastname: Mari
authors.forename: Matthias
authors.initials: M
authors.lastname: Edinger
authors.forename: Robert S
authors.initials: RS
authors.lastname: Negrin
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Tait
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Contag
authors.forename: Francis G
authors.initials: FG
authors.lastname: Blankenberg
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000493:pharmacokinetics; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D004317:Doxorubicin / Q000633:toxicity; D005260:Female; D049452:Green Fluorescent Proteins; D007275:Injections, Intravenous; D008156:Luciferases / Q000378:metabolism; D008163:Luminescent Measurements; D008164:Luminescent Proteins / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D017304:Annexin A5; D000903:Antibiotics, Antineoplastic; D008164:Luminescent Proteins; D015609:Organotechnetium Compounds; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; D049452:Green Fluorescent Proteins; D004317:Doxorubicin; D008156:Luciferases