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Sökning: (WFRF:(Vorobyeva Anzhelika)) > (2020) > Evaluation of an an...

Evaluation of an antibody-PNA conjugate as a clearing agent for antibody-based PNA-mediated radionuclide pretargeting

Myrhammar, Anders (författare)
KTH Royal Institute of Technology,KTH,Proteinvetenskap,Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, Stockholm, Sweden.
Vorobyeva, Anzhelika (författare)
Uppsala University,Uppsala universitet,Medicinsk strålningsvetenskap,Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, Tomsk, Russia,Vladimir Tolmachev,Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk, Russia.
Westerlund, Kristina (författare)
KTH Royal Institute of Technology,KTH,Proteinvetenskap
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Yoneoka, Shuichiro (författare)
Tokyo Inst Technol, Lab Adv Nucl Energy, Tokyo, Japan.,Tokyo Institute of Technology
Orlova, Anna, 1960- (författare)
Uppsala University,Uppsala universitet,Institutionen för läkemedelskemi,Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, Tomsk, Russia,Anna Orlova,Uppsala Univ, Dept Med Chem, Uppsala, Sweden.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk, Russia.
Tsukahara, Takehiko (författare)
Tokyo Inst Technol, Lab Adv Nucl Energy, Tokyo, Japan.,Tokyo Institute of Technology
Tolmachev, Vladimir (författare)
Uppsala University,Uppsala universitet,Medicinsk strålningsvetenskap,Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, Tomsk, Russia,Vladimir Tolmachev,Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk, Russia.
Eriksson Karlström, Amelie (författare)
KTH Royal Institute of Technology,KTH,Proteinvetenskap
Altai, Mohamed (författare)
Lund University,Lunds universitet,Division of Oncology and Pathology, Kamprad Lab, Department of Clinical Sciences, Lund University, Lund, Sweden,Lund Univ, Div Oncol & Pathol, Dept Clin Sci, Kamprad Lab, Lund, Sweden.,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Systemisk strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Systemic radiation therapy,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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 (creator_code:org_t)
2020-11-27
2020
Engelska.
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
Relaterad länk:
https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
https://www.nature.c...
http://dx.doi.org/10... (free)
https://urn.kb.se/re...
https://doi.org/10.1...
https://urn.kb.se/re...
https://lup.lub.lu.s...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Radionuclide molecular imaging of cancer-specific targets is a promising method to identify patients for targeted antibody therapy. Radiolabeled full-length antibodies however suffer from slow clearance, resulting in high background radiation. To overcome this problem, a pretargeting system based on complementary peptide nucleic acid (PNA) probes has been investigated. The pretargeting relies on sequential injections of primary, PNA-tagged antibody and secondary, radiolabeled PNA probe, which are separated in time, to allow for clearance of non-bound primary agent. We now suggest to include a clearing agent (CA), designed for removal of primary tumor-targeting agent from the blood. The CA is based on the antibody cetuximab, which was conjugated to PNA and lactosaminated by reductive amination to improve hepatic clearance. The CA was evaluated in combination with PNA-labelled trastuzumab, T-ZHP1, for radionuclide HER2 pretargeting. Biodistribution studies in normal mice demonstrated that the CA cleared ca. 7 times more rapidly from blood than unmodified cetuximab. Injection of the CA 6 h post injection of the radiolabeled primary agent [131I]I-T-ZHP1 gave a moderate reduction of the radioactivity concentration in the blood after 1 h from 8.5 ± 1.8 to 6.0 ± 0.4%ID/g. These proof-of-principle results could guide future development of a more efficient CA.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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