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Influence of pegylation and hapten location at the surface of radiolabelled liposomes on tumour immunotargeting using bispecific antibody
Abstract Introduction This paper proposes liposomes as a potential new tool for radioimmunotherapy in solid tumours with a two step targeting system. Tumour pretargeting is obtained by using a monoclonal bispecific antibody (BsmAb, anti CEA x anti-DTPA-In) and pegylated liposomes containing lipid-ha...
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Published in: | Nuclear medicine and biology 2014-05, Vol.41, p.e66-e74 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Abstract Introduction This paper proposes liposomes as a potential new tool for radioimmunotherapy in solid tumours with a two step targeting system. Tumour pretargeting is obtained by using a monoclonal bispecific antibody (BsmAb, anti CEA x anti-DTPA-In) and pegylated liposomes containing lipid-hapten (DSPE-DTPA-In or DSPE-PEG-DTPA-In). To optimise at the same time in vivo behaviour and specific targeting, the study focuses on the liposome formulation in order to determine more precisely the role of pegylation on both the blood half-life and the specific recognition with the BsmAb. Methods Different liposome formulations containing two PEG length (1000 and 2000) in varying amount (1.5–6 mol%) were prepared with DTPA directly coupled to DSPE or at the end of the PEG chain (DSPE-DTPA or DSPE-PEG-DTPA). Liposomes were immobilized on an L1 chip to measure by SPR (Surface Plasmon Resonance) the effect of pegylation on the BsmAb recognition of the DTPA-In hapten. Pharmacokinetic studies were performed in mice. Tumour targeting was studied in nude mice xenografted with human colorectal adenocarcinoma cells that express CEA, and doubly radiolabelled liposomes (with111 In and125 I) injected 24 h after the BsmAb. Results The best in vitro apparent dissociation constant was obtained with liposomes bearing DTPA at the end of the PEG chain ( KD = 6.3 nM), which showed significant specific tumour uptake after BsmAb injection (8.6 ± 2.4% ID/g at 24 h versus 4.5 ± 0.5%ID/g for passive targeting, α = 0.01). All tumour/organ ratios were superior to 1 at 24 h for this formulation, except for the spleen. Conclusion The feasibility of specific tumour targeting in mice with a BsmAb and radiolabelled liposomes was demonstrated and the interest of SPR to predict their targeting performance in vivo was highlighted. This original and new approach provides promising prospects for the radioimmunotherapy of solid tumours. |
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ISSN: | 0969-8051 1872-9614 |
DOI: | 10.1016/j.nucmedbio.2013.12.012 |