Preclinical Evaluation of 18F-ML-10 to Determine Timing of Apoptotic Response to Chemotherapy in Solid Tumors

Mol Imaging. 2017 Jan 1:16:1536012116685941. doi: 10.1177/1536012116685941.

Abstract

Purpose: 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.

Procedures: 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.

Results: 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.

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.

Keywords: 18F-ML-10; PET; apoptosis; early response; molecular imaging.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cell Line, Tumor
  • Doxorubicin / pharmacology
  • Female
  • Fluorodeoxyglucose F18 / analysis*
  • Humans
  • Immunohistochemistry
  • Methylmalonic Acid / analogs & derivatives*
  • Methylmalonic Acid / analysis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Positron-Emission Tomography / methods*
  • Tomography, X-Ray Computed
  • Xenograft Model Antitumor Assays

Substances

  • 5-fluoropentyl-2-methylmalonic acid
  • Fluorodeoxyglucose F18
  • Doxorubicin
  • Methylmalonic Acid