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

Journal Article · Mon Jan 09 23:00:00 EST 2017 · Molecular Imaging

DOI: https://doi.org/10.1177/1536012116685941 · OSTI ID:1366738

Demirci, Emre ^[1]; Ahmed, Rafay ^[2]; Ocak, Meltem ^[3]; Latoche, Joseph ^[2]; Radelet, April ^[2]; DeBlasio, Nicole ^[2]; Mason, N. Scott ^[2]; Anderson, Carolyn J. ^[2]; Mountz, James M. ^[2]

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1. Univ. of Pittsburgh, Pittsburgh, PA (United States); Sisli Etfal Training and Research Hospital, Istanbul (Turkey); University of Pittsburgh
2. Univ. of Pittsburgh, Pittsburgh, PA (United States)
3. Univ. of Pittsburgh, Pittsburgh, PA (United States); Istanbul Univ., Istanbul (Turkey)

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.

• Research Organization: Univ. of Pittsburgh, Pittsburgh, PA (United States)
• Sponsoring Organization: USDOE Office of Science (SC)
• Grant/Contract Number: SC0008833
• OSTI ID: 1366738
• Journal Information: Molecular Imaging, Journal Name: Molecular Imaging Vol. 16; ISSN 1536-0121
• Country of Publication: United States
• Language: English