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- Title
Scintigraphic imaging of P-glycoprotein expression with a radiolabelled antibody.
- Authors
van Eerd, Julliëtte E. M.; de Geus-Oei, Lioe-Fee; Oyen, Wim J. G.; Corstens, Frans H. M.; Boerman, Otto C.
- Abstract
P-glycoprotein (P-gp) is a membrane efflux pump protein that is involved in multidrug resistance (MDR). Tumour cells with high P-gp expression show poor response to cancer treatment with several chemotherapeutics. In vivo targeting and visualisation of P-gp expression would allow MDR to be evaluated non-invasively prior to treatment. The aim of this study was to investigate the feasibility of visualising P-gp expression in tumours using a monoclonal anti-P-gp antibody, 15D3. Nude BALB/c mice with subcutaneously growing human uterine sarcoma cell tumours with either high (MES-SA/D×5 1977) or low (MES-SA 1976) P-gp expression were used. When tumours were 0.2–0.4 g, mice received 131I-15D3 or 111In-DTPA-15D3 monoclonal anti-P-gp antibody intravenously. Images were acquired up to 3 days p.i. and radioactivity concentration in various tissues was determined after euthanisation of the animals. The images demonstrated that radioactivity accumulated to a higher concentration in high P-gp expressing tumours than in the low P-gp expressing MES-SA 1976 tumour. Furthermore, visualisation of the P-gp expressing tumours was superior with 111In-DTPA-15D3 than with 131I-15D3. After injection of 111In-DTPA-15D3, the high P-gp expressing MES-SA/D×5 1977 tumours were clearly visualised at 3 days p.i. The biodistribution data indicated that radioactivity concentration in the high P-gp expressing tumours was higher than in the tumours with low P-gp expression (20.78±1.42 %ID/g for MES-SA/Dx5 1977 tumours and 8.39±3.78 %ID/g for MES-SA 1976 tumours for 111In-DTPA-15D3). The 111In-labelled monoclonal anti-P-gp antibody clearly visualised P-gp expression in a human uterine sarcoma tumour in nude mice.
- Subjects
POSITRON emission tomography; P-glycoprotein; MULTIDRUG resistance; MONOCLONAL antibodies; CANCER cells; CANCER treatment; SARCOMA; NUDE mouse
- Publication
European Journal of Nuclear Medicine & Molecular Imaging, 2006, Vol 33, Issue 11, p1266
- ISSN
1619-7070
- Publication type
Article
- DOI
10.1007/s00259-006-0152-0