Abstract | OBJECTIVE: Technetium-99m sestamibi (MIBI) has been utilized to evaluate multi-drug resistance (MDR) phenomenon of malignant tumors and to predict chemotherapeutic effects on them. The current investigation examined the possibility of monitoring changes with respect to mRNA expression of multi-drug resistance associated protein (MRP) following antisense oligodeoxynucleotide (AS-ODN) treatment involving 99mTc-MIBI. METHODS: The human breast cancer MCF-7 cell line and its MDR-induced MCF-7/VP cell line were employed. Cell suspensions of the two cell lines at 1 x 10(4) cells/ml were inoculated in 24-well plates (0.2 ml/well) and incubated for one day. Antisense (AS) 20-mer phosphorothioate ODN complementary to the coding region of MRP mRNA and its sense (S) ODN were administered at final concentrations up to 25 microM, followed by a 5-day incubation. 99mTc-MIBI solution was added to each well and incubated for 30 min. Cellular 99mTc-MIBI uptake was corrected for protein concentration. MRP mRNA expression levels were analyzed via the reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Cellular uptake of 99mTc-MIBI in MCF-7/VP cells was only 15% of that of MCF-7 cells. Following AS-ODN treatment at 25 microM for five days, 99mTc-MIBI uptake in MCF-7/VP cells increased 2.4-fold in comparison with non-treated control cells. 99mTc-MIBI uptake in MCF-7 cells was unaffected by AS-ODN administration. Sense ODN did not alter uptake in either cell line. RT-PCR confirmed reduction of MRP mRNA in MCF-7/VP cells following AS-ODN treatment. CONCLUSION: Effects of AS-ODN administration on MRP function can be monitored via assessment of cellular uptake of 99mTc-MIBI.
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Authors | Seigo Kinuya, Jingming Bai, Kazuhiro Shiba, Kunihiko Yokoyama, Hirofumi Mori, Makoto Fukuoka, Naoto Watanabe, Noriyuki Shuke, Takatoshi Michigishi, Norihisa Tonami |
Journal | Annals of nuclear medicine
(Ann Nucl Med)
Vol. 20
Issue 1
Pg. 29-34
(Jan 2006)
ISSN: 0914-7187 [Print] Japan |
PMID | 16485571
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Multidrug Resistance-Associated Proteins
- Oligodeoxyribonucleotides, Antisense
- RNA, Messenger
- Radiopharmaceuticals
- Technetium Tc 99m Sestamibi
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Topics |
- Breast Neoplasms
(diagnostic imaging, genetics, metabolism, therapy)
- Cell Line, Tumor
- Genetic Therapy
(methods)
- Humans
- Metabolic Clearance Rate
- Multidrug Resistance-Associated Proteins
(genetics, metabolism)
- Oligodeoxyribonucleotides, Antisense
(administration & dosage, genetics)
- Prognosis
- RNA, Messenger
(genetics)
- Radionuclide Imaging
- Radiopharmaceuticals
(pharmacokinetics)
- Technetium Tc 99m Sestamibi
(pharmacokinetics)
- Treatment Outcome
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