Abstract
The study objective was to investigate whether sex influences 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) uptake and tissue distribution in mouse models of cancer. Methods: 18F-FLT biodistribution was measured in three strains of male and female mice (129S6/SvEv, athymic nude, and BALB/c). 18F-Fluoro-2-deoxy-2-D-glucose (18F-FDG) biodistribution was performed for comparison. 18F-FLT uptake was also measured in female 129S6/SvEv mice bearing estrogen-dependent SSM3 mouse mammary tumors, male athymic nude mice bearing androgen-dependent CWR22 prostate cancer xenografts, and male and female athymic nude mice bearing estrogen-independent MDA-MB-231 human breast cancer xenografts. Ki67 expression was assayed by immunohistochemistry. Positron emission tomography/computed tomography (PET/CT) imaging was performed to visualize 18F-FLT biodistribution and for pharmacokinetics. Results: Greater 18F-FLT activity was observed in blood, liver, muscle, heart, kidney, and bone in female mice compared to males. Pharmacokinetic analysis demonstrated early increased renal 18F-FLT activity and greater accumulation of 18F-FLT in the urinary bladder in male mice compared with females. The differential pattern of 18F-FLT biodistribution between the sexes seen with 18F-FLT was not observed with 18F-FDG. Increased tumoral 18F-FLT uptake compared with muscle was observed in both the SSM3 mammary tumors (2.4±0.17 vs 1.6±0.14%ID/g at 2 h post-injection, P = 0.006) and CWR22 prostate cancer xenografts (0.34±0.08 vs 0.098±0.033%ID/g at 2 h post-injection, P = 0.03). However, due to higher nonspecific muscle uptake in female mice, tumor-to-muscle (T:M) uptake ratios were greater for CWR22 tumors compared with SSM3 tumors (4.2±0.78 vs 1.5±0.049 at 2 h post-injection, P = 0.008). Sex-dependent differences in 18F-FLT uptake was also observed for MDA-MB-231 xenografts (T:M ratios 7.2±0.9 female vs 16.9±8.6 male; P = 0.039) . Conversely, greater tumoral Ki67 staining was observed in female mice (71±3% female vs 54±2% male; P = 0.009) which more closely matched the relative differences in absolute 18F-FLT tumor uptake values (4.5±0.99%ID/g female vs 1.9±0.30%ID/g male; P = 0.03). Conclusion: Depending on whether female or male mice are used, differences in biodistribution and nonspecific tissue uptake can adversely impact quantitative measures of 18F-FLT uptake. Thus, sex is a potential variable to consider in defining quantitative imaging metrics using 18F-FLT to assess tumor proliferation.
- Animal Imaging
- Oncology: Breast
- Radiopharmaceuticals
- 3'-deoxy-3'-[18F]fluorothymidine
- Cancer
- Mice
- Positron emission tomography
- Sex differences
- Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.