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Title: Preclinical evaluation of 18F-ML-10 to determine timing of apoptotic response to chemotherapy in solid tumors

Abstract

Here, we investigated 2-(5-fluoro-pentyl)-2-methyl-malonic acid (18F-ML-10) positron emission tomography (PET) imaging of apoptosis posttherapy to determine optimal timing for predicting chemotherapy response in a mouse head/neck xenograft cancer model. BALB/c nude mice (4-8 weeks old) were implanted with UM-SCC-22B tumors. The treatment group received 2 doses of doxorubicin (10 mg/kg, days 0, 2). Small animal 18F-ML-10 PET/computed tomography was performed before and on days 1, 3, and 7 postchemotherapy. Using regions of interest around tumors, 18F-ML-10 uptake change was measured as %ID/g and uptake relative to liver. Terminal Uridine Nick-End Labeling (TUNEL) immunohistochemistry assay was performed using tumor samples of baseline and on days 1, 3, and 7 posttreatment. As a result, treated mice demonstrated increased 18F-ML-10 uptake compared to baseline and controls, and 10 of 13 mice showed tumor volume decreases. All control mice showed tumor volume increases. Tumor-to-liver (T/L) ratios from the control group mice did not show significant change from baseline (P > .05); however, T/L ratios of the treatment group showed significant 18F-ML-10 uptake differences from baseline compared to days 3 and 7 posttreatment (P < .05), but no significant difference at 1 day posttreatment. In conclusion, 2-(5-Fluoro-pentyl)-2-methyl-malonic acid PET imaging has the potential for earlymore » assessment of treatment-induced apoptosis. Timing and image analysis strategies may require optimization, depending on the type of tumor and cancer treatment.« less

Authors:
 [1];  [2];  [3];  [2];  [2];  [2];  [2];  [2];  [2]
+ Show Author Affiliations
  1. Univ. of Pittsburgh, Pittsburgh, PA (United States); Sisli Etfal Training and Research Hospital, Istanbul (Turkey)
  2. Univ. of Pittsburgh, Pittsburgh, PA (United States)
  3. Univ. of Pittsburgh, Pittsburgh, PA (United States); Istanbul Univ., Istanbul (Turkey)
Publication Date:
Research Org.:
Univ. of Pittsburgh, PA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1366738
Grant/Contract Number:  
SC0008833
Resource Type:
Accepted Manuscript
Journal Name:
Molecular Imaging
Additional Journal Information:
Journal Volume: 16; Journal ID: ISSN 1536-0121
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; molecular imaging; apoptosis; early response; 18F-ML-10; PET

Citation Formats

Demirci, Emre, Ahmed, Rafay, Ocak, Meltem, Latoche, Joseph, Radelet, April, DeBlasio, Nicole, Mason, N. Scott, Anderson, Carolyn J., and Mountz, James M. Preclinical evaluation of 18F-ML-10 to determine timing of apoptotic response to chemotherapy in solid tumors. United States: N. p., 2017. Web. doi:10.1177/1536012116685941.
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Demirci, Emre, Ahmed, Rafay, Ocak, Meltem, Latoche, Joseph, Radelet, April, DeBlasio, Nicole, Mason, N. Scott, Anderson, Carolyn J., & Mountz, James M. Preclinical evaluation of 18F-ML-10 to determine timing of apoptotic response to chemotherapy in solid tumors. United States. https://doi.org/10.1177/1536012116685941
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Demirci, Emre, Ahmed, Rafay, Ocak, Meltem, Latoche, Joseph, Radelet, April, DeBlasio, Nicole, Mason, N. Scott, Anderson, Carolyn J., and Mountz, James M. Tue . "Preclinical evaluation of 18F-ML-10 to determine timing of apoptotic response to chemotherapy in solid tumors". United States. https://doi.org/10.1177/1536012116685941. https://www.osti.gov/servlets/purl/1366738.
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@article{osti_1366738,
title = {Preclinical evaluation of 18F-ML-10 to determine timing of apoptotic response to chemotherapy in solid tumors},
author = {Demirci, Emre and Ahmed, Rafay and Ocak, Meltem and Latoche, Joseph and Radelet, April and DeBlasio, Nicole and Mason, N. Scott and Anderson, Carolyn J. and Mountz, James M.},
abstractNote = {Here, we investigated 2-(5-fluoro-pentyl)-2-methyl-malonic acid (18F-ML-10) positron emission tomography (PET) imaging of apoptosis posttherapy to determine optimal timing for predicting chemotherapy response in a mouse head/neck xenograft cancer model. BALB/c nude mice (4-8 weeks old) were implanted with UM-SCC-22B tumors. The treatment group received 2 doses of doxorubicin (10 mg/kg, days 0, 2). Small animal 18F-ML-10 PET/computed tomography was performed before and on days 1, 3, and 7 postchemotherapy. Using regions of interest around tumors, 18F-ML-10 uptake change was measured as %ID/g and uptake relative to liver. Terminal Uridine Nick-End Labeling (TUNEL) immunohistochemistry assay was performed using tumor samples of baseline and on days 1, 3, and 7 posttreatment. As a result, treated mice demonstrated increased 18F-ML-10 uptake compared to baseline and controls, and 10 of 13 mice showed tumor volume decreases. All control mice showed tumor volume increases. Tumor-to-liver (T/L) ratios from the control group mice did not show significant change from baseline (P > .05); however, T/L ratios of the treatment group showed significant 18F-ML-10 uptake differences from baseline compared to days 3 and 7 posttreatment (P < .05), but no significant difference at 1 day posttreatment. In conclusion, 2-(5-Fluoro-pentyl)-2-methyl-malonic acid PET imaging has the potential for early assessment of treatment-induced apoptosis. Timing and image analysis strategies may require optimization, depending on the type of tumor and cancer treatment.},
doi = {10.1177/1536012116685941},
journal = {Molecular Imaging},
number = ,
volume = 16,
place = {United States},
year = {Tue Jan 10 00:00:00 EST 2017},
month = {Tue Jan 10 00:00:00 EST 2017}
}
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https://doi.org/10.1177/1536012116685941
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    Works referencing / citing this record:

    Evaluation of apoptosis imaging biomarkers in a genetic model of cell death
    journal, February 2019

    [18F]ML-10 PET imaging fails to assess early response to neoadjuvant chemotherapy in a preclinical model of triple negative breast cancer
    journal, January 2020

    • Jouberton, Elodie; Schmitt, Sébastien; Chautard, Emmanuel
    • EJNMMI Research, Vol. 10, Issue 1
    • DOI: 10.1186/s13550-019-0587-5
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