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[(177)Lu]pertuzumab :
[(177)Lu]pertuzumab : experimental studies on targeting of HER-2 positive tumour cells
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- Persson, Mikael (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Andersson, Karl (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Gedda, Lars (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Sandström, Mattias (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Carlsson, Jörgen (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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(creator_code:org_t)
- 2005-09-29
- 2005
- Engelska.
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 32:12, s. 1457-62
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- PURPOSE: The new antibody pertuzumab (Omnitarg) targets the dimerisation subdomain of HER-2. The purpose of this study was to analyse whether pertuzumab retains HER-2 targeting capacity after labelling with the therapeutically interesting beta emitter (177)Lu and to make initial characterizations in vitro and in vivo. METHODS: Pertuzumab was conjugated with isothiocyanate-benzyl-CHX-A''-DTPA and chelated to (177)Lu. Immunoreactivity, affinity, cellular retention and internalisation were analysed using SKOV-3 cells. The affinity of non-radioactive pertuzumab was measured using a surface plasmon resonance biosensor. In vivo targeting and specific binding were assessed in Balb/c (nu/nu) mice carrying SKOV-3 xenografts. The biodistribution of (177)Lu was determined 1, 3 and 7 days after [(177)Lu]pertuzumab administration. Gamma camera images were taken after 3 days. RESULTS: The immunoreactivity of [(177)Lu]pertuzumab was 85.8+/-1.3%. The affinity of non-radioactive pertuzumab was 1.8+/-1.1 nM, and that of [(177)Lu]pertuzumab, 4.1+/-0.7 nM. The cellular retention after 5 h pre-incubation was 90+/-2% at 20 h. The targeting was HER-2 specific both in vitro and in vivo, since excess amounts of non-labelled antibody inhibited the uptake of labelled antibody (p<0.0001 and p<0.01, respectively). The biodistribution and gamma camera images of (177)Lu showed extensive tumour uptake. Normal tissues had a surprisingly low uptake. CONCLUSION: Pertuzumab was efficiently labelled with (177)Lu and showed good intracellular retention and HER-2 specific binding both in vitro and in vivo. The gamma camera images and the biodistribution study gave excellent tumour targeting results. Thus, [(177)Lu]pertuzumab is of interest for further studies aimed at radionuclide therapy.
Nyckelord
- Cancer
- Tumor
- Radiation
- Therapy
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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