Scintigraphic imaging of P-glycoprotein expression with a radiolabelled antibody.
OBJECTIVE
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.


METHODS
Nude BALB/c mice with subcutaneously growing human uterine sarcoma cell tumours with either high (MES-SA/Dx5 1977) or low (MES-SA 1976) P-gp expression were used. When tumours were 0.2-0.4 g, mice received (131)I-15D3 or (111)In-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.


RESULTS
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 (111)In-DTPA-15D3 than with (131)I-15D3. After injection of (111)In-DTPA-15D3, the high P-gp expressing MES-SA/Dx5 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 (111)In-DTPA-15D3).


CONCLUSIONS
The (111)In-labelled monoclonal anti-P-gp antibody clearly visualised P-gp expression in a human uterine sarcoma tumour in nude mice.
van Eerd
Julliëtte E M
JE
Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. J.vaneerd@nucmed.umcn.nl
de Geus-Oei
Lioe-Fee
LF
Oyen
Wim J G
WJ
Corstens
Frans H M
FH
Boerman
Otto C
OC
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D005240:Feasibility Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011877:Radionuclide Imaging; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014594:Uterine Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes