Abstract 2498
Background
Limited data are available on 5FU intratumoral pharmacokinetics. Previous studies with radiolabeled 5FU showed homogeneous uptake in spheroids within a few minutes (Cancer Chemother Pharmacol. 1984;13(2):131-5) but no quantification was done. We present data on intracellular and intra-spheroidal 5FU uptake; drug efflux experiments are on-going and results will be presented.
Methods
MCF-7 and HCT-116 cells were used for cellular and spheroid experiments. Spheroid growth was optimized to produce a spheroid of 300-400 µm diameter at day 4. Treatment: 1x106 cells or 30 spheroids/time point were exposed to 10 µM (1300ng/mL) 5FU at
Results
Both MCF-7 and HCT-116 achieved steady state by 20min in cells (1800ng/g aprox.) and 60min in spheroids (330ng/g aprox.) that was maintained at 240min. No 5FUrd was seen but 5FdUrd was identified in the HCT-116 cell line; with 5FdUrd included, total drug levels at steady state were 3000ng/g and 1000ng/g in cells and spheroids, respectively. Although there was variability in the HCT-116 drug levels between experiments, the contour of the drug uptake curve was consistent. MCF-7 spheroids are being analyzed.
5FU uptake ng/g Mean [range]
| Min | HCT-116 cells | MCF-7 cells | HCT-116 spheroids |
|---|---|---|---|
ConclusionsOur results suggest that 5FU is rapidly taken up into cells and spheroids, being less prominent in spheroids. These data and methodology may be useful to allow generation of mathematical models to improve drug delivery. Clinical trial identificationNot applicable Legal entity responsible for the studyInstitute Cancer Therapeutics (Bradford University) / University of Leeds FundingInstitute Cancer Therapeutics Spanish Medical Oncology Society DisclosureAll authors have declared no conflicts of interest. Resources from the same session2354 - The clinicopathologic features and treatment of 607 hindgut neuroendocrine tumor (NET) patients at a single institutionPresenter: Seung Tae Kim Session: Poster Display Resources: Abstract 2594 - Neuroendocrine carcinomas of the colorectal origin - Polish experiencePresenter: Agnieszka Kolasińska-Ćwikła Session: Poster Display Resources: Abstract 2539 - Neuroendocrine neoplasms of the appendix including goblet cell carcinoidsPresenter: Agnieszka Kolasinska-Cwikla Session: Poster Display Resources: Abstract 1245 - Prognostic validity of AJCC staging system in neuroendocrine tumors of the appendixPresenter: Amir Mehrvarz Sarshekeh Session: Poster Display Resources: Abstract 3902 - Enhancer of zest homolog 2 (EZH2) expression in well and moderately differentiated pancreatic neuroendocrine tumor (pNET)Presenter: Riccardo Marconcini Session: Poster Display Resources: Abstract 3882 - Differential clinical and pathological characteristics of hereditary neuroendocrine pancreatic tumours (NEPT)Presenter: Gema Marín Zafra Session: Poster Display Resources: Abstract 2296 - Natural course of thyroid cancer nodules compared with benign thyroid nodulesPresenter: Kyung-Jin Yun Session: Poster Display Resources: Abstract 4083 - Reassessment of proliferative activity at disease progression in neuroendocrine neoplasmsPresenter: Noemi Cicchese Session: Poster Display Resources: Abstract 3866 - 18F-FDG-PET to predict disease progression in advanced digestive neuroendocrine neoplasmsPresenter: Maria Rinzivillo Session: Poster Display Resources: Abstract 3651 - UK phase IV, observational study to assess quality of life in patients (pts) with pancreatic neuroendocrine tumours (pNETS) receiving treatment with everolimus: The “real-world” OBLIQUE studyPresenter: John Ramage Session: Poster Display Resources: Abstract This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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