Journal article
Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice
Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. mettemj@sund.ku.dk1
3'-Deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) is a tracer used to assess cell proliferation in vivo. The aim of the study was to use (18)F-FLT positron emission tomography (PET) to study treatment responses to a new anti-cancer compound. To do so, we studied early anti-proliferative effects of the experimental chemotherapy Top216 non-invasively by PET.
In vivo uptake of (18)F-FLT in human ovary cancer xenografts in mice (A2780) was studied at various time points after Top216 treatment (50 mg/kg i.v. at 0 and 48 hours) was initiated. Baseline (18)F-FLT scans were made before either Top216 (n = 7-10) or vehicle (n = 5-7) was injected and repeated after 2 and 6 hours and 1 and 5 days of treatment.
A parallel study was made with 2'-deoxy-2'-[(18)F]fluoro-D-glucose ((18)F-FDG) (n = 8). Tracer uptake was quantified using small animal PET/CT. Imaging results were validated by tumor volume changes and gene-expression of Ki67 and TK1. Top216 (50 mg/kg 0 and 48 hours) inhibited the growth of the A2780 tumor compared to the control group (P<0.001). (18)F-FLT uptake decreased significantly at 2 hours (-52%; P<0.001), 6 hours (-49%; P = 0.002) and Day 1 (-47%; P<0.001) after Top216 treatment.
At Day 5 (18)F-FLT uptake was comparable to uptake in the control group. Uptake of (18)F-FLT was unchanged in the control group during the experiment. In the treatment group, uptake of (18)F-FDG was significantly decreased at 6 hours (-21%; P = 0.003), Day 1 (-29%; P<0.001) and Day 5 (-19%; P = 0.05) compared to baseline.
One injection with Top216 initiated a fast and significant decrease in cell-proliferation assessable by (18)F-FLT after 2 hours. The early reductions in tumor cell proliferation preceded changes in tumor size. Our data indicate that (18)F-FLT PET is promising for the early non-invasive assessment of chemotherapy effects in both drug development and for tailoring therapy in patients.
| Language: | English |
|---|---|
| Publisher: | Public Library of Science |
| Year: | 2010 |
| Pages: | e12965 |
| ISSN: | 19326203 , 15537358 and 1553734x |
| Types: | Journal article |
| DOI: | 10.1371/journal.pone.0012965 |
| ORCIDs: | Björkling, Fredrik and Kjær, Andreas |
Animals Antineoplastic Agents Cell Proliferation Dideoxynucleosides Disease Models, Animal Drug Monitoring Female Fluorodeoxyglucose F18 Humans Medicine Mice Mice, Nude Ovarian Neoplasms Positron-Emission Tomography Q R Radiopharmaceuticals Science Xenograft Model Antitumor Assays alovudine
