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

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

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., Web. doi:10.1177/1536012116685941.
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. doi:10.1177/1536012116685941.
Demirci, Emre, Ahmed, Rafay, Ocak, Meltem, Latoche, Joseph, Radelet, April, DeBlasio, Nicole, Mason, N. Scott, Anderson, Carolyn J., and Mountz, James M.. 2017. "Preclinical evaluation of 18F-ML-10 to determine timing of apoptotic response to chemotherapy in solid tumors". United States. doi:10.1177/1536012116685941. https://www.osti.gov/servlets/purl/1366738.
@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 = {2017},
month = {1}
}