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Preclinical Evaluat...
Preclinical Evaluation of Tc-99m-ZHER2:41071, a Second-Generation Affibody-Based HER2-Visualizing Imaging Probe with a Low Renal Uptake
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- Oroujeni, Maryam, PhD, 1982- (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Rinne, Sara S. (author)
- Uppsala universitet,Theranostics
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- Vorobyeva, Anzhelika (author)
- Uppsala universitet,Medicinsk strålningsvetenskap,Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden.;Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.
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- Loftenius, Annika (author)
- Affibody AB, S-17165 Solna, Sweden.
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- Feldwisch, Joachim (author)
- Affibody AB, S-17165 Solna, Sweden.
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- Jonasson, Per (author)
- Affibody AB, S-17165 Solna, Sweden.
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- Chernov, Vladimir (author)
- Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.;Russian Acad Sci, Tomsk Natl Res Med Ctr, Canc Res Inst, Nucl Med Dept, Tomsk 634009, Russia.
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- Orlova, Anna, 1960- (author)
- Uppsala universitet,Medicinsk strålningsvetenskap,Theranostics,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden.;Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.
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- Frejd, Fredrik Y. (author)
- Uppsala universitet,Medicinsk strålningsvetenskap,Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden.;Affibody AB, S-17165 Solna, Sweden.
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- Tolmachev, Vladimir (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Medicinsk strålningsvetenskap,Radiologi,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden.;Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden.
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(creator_code:org_t)
- 2021-03-09
- 2021
- English.
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In: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:5
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Abstract
Subject headings
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- Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [Tc-99m]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface. In this study, a second-generation affibody molecule (designated ZHER2:41071) with a new improved scaffold has been prepared and characterized. HER2-binding, biodistribution, and tumour-targeting properties of [Tc-99m]Tc-labelled ZHER2:41071 were investigated. These properties were compared with properties of the first-generation affibody molecules, [Tc-99m]Tc-ZHER2:V2 and [Tc-99m]Tc-ZHER2:2395. [Tc-99m]Tc-ZHER2:41071 bound specifically to HER2 expressing cells with an affinity of 58 +/- 2 pM. The renal uptake for [Tc-99m]Tc-ZHER2:41071 and [Tc-99m]Tc-ZHER2:V2 was 25-30 fold lower when compared with [Tc-99m]Tc-ZHER2:2395. The uptake in tumour and kidney for [Tc-99m]Tc-ZHER2:41071 and [Tc-99m]Tc-ZHER2:V2 in SKOV-3 xenografts was similar. In conclusion, an extensive re-engineering of the scaffold did not compromise imaging properties of the affibody molecule labelled with Tc-99m using a GGGC chelator. The new probe, [Tc-99m]Tc-ZHER2:41071 provided the best tumour-to-blood ratio compared to HER2-imaging probes for single photon emission computed tomography (SPECT) described in the literature so far. [Tc-99m]Tc-ZHER2:41071 is a promising candidate for further clinical translation studies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
- LANTBRUKSVETENSKAPER -- Lantbruksvetenskap, skogsbruk och fiske -- Livsmedelsvetenskap (hsv//swe)
- AGRICULTURAL SCIENCES -- Agriculture, Forestry and Fisheries -- Food Science (hsv//eng)
Keyword
- HER2
- radionuclide molecular imaging
- affibody molecule
- technetium-99m
- second-generation scaffold
Publication and Content Type
- ref (subject category)
- art (subject category)
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Oroujeni, Maryam ...
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Rinne, Sara S.
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Vorobyeva, Anzhe ...
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Loftenius, Annik ...
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Feldwisch, Joach ...
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Jonasson, Per
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Chernov, Vladimi ...
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Orlova, Anna, 19 ...
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Frejd, Fredrik Y ...
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Tolmachev, Vladi ...
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Uppsala University