Preclinical assessment of early tumor response after irradiation by positron emission tomography with 2-amino-[3-11C]isobutyric acid

Abstract

The positron emission tomography (PET) probe, 2-amino-[3-11C]isobutyric acid ([3-11C]AIB), is reported to accumulate less in inflammatory lesions than 2-deoxy-2-[18F] fluoro-D-glucose ([18F]FDG) and has the potential for evaluation of the efficacy of radiotherapy. To determine whether [3-11C]AIB is useful to monitor early metabolic change in tumors after radiotherapy, we evaluated the temporal change in [3-11C]AIB tumor uptake, tumor volume, histological features and expression of amino acid transporters early after radiotherapy in a mouse tumor model. PET with [3-11C]AIB was conducted in mice bearing a subcutaneous tumor (SY, derived from small cell lung cancer) in two schedules: schedule 1, before (day-1) and after (days 1 and 3) 15 Gy of radiation and schedule 2, days-1, 1 and 5. [3-11C]AIB tumor uptake tended to increase on day 1 after irradiation and decreased thereafter. Tumor uptake was not correlated with tumor volume in schedule 1. Although tumor uptake was correlated with tumor volume in schedule 2, this correlation was lost when the day 5 data of greatly reduced tumor volumes were excluded. In a separate group of tumor-bearing mice, excised tumor sections were stained with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) or anti-Ki-67 antibody. There was no correlation between tumor uptake and percentages of TUNEL- or Ki-67-positive cells. Expression of amino acid transporters, SLC38A1, SLC38A2 and SLC38A4, was determined by real-time RT-PCR. SLC38A1 and SLC38A2 were expressed in SY tumors, and a significant correlation was observed between [3-11C]AIB tumor uptake and SLC38A1 expression. In conclusion, early change in [3-11C]AIB tumor uptake after irradiation reflected the temporal change in amino acid transporter expression, while it was independent of change in tumor volume, apoptosis and cell proliferation. PET with [3-11C]AIB has the potential for use in non-invasive evaluation of early metabolic change after irradiation before morphological change of tumors.