Imaging of HER3-expressing xenografts in mice using a Tc-99m(CO)(3)-HEHEHE-Z(HER3:08699) affibody molecule

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Imaging of HER3-expressing xenografts in mice using a Tc-99m(CO)(3)-HEHEHE-Z(HER3:08699) affibody molecule

Orlova, Anna (author): Uppsala universitet,Plattformen för preklinisk PET

Malm, Magdalena (author): KTH,Proteinteknologi

Rosestedt, Maria (author): Uppsala universitet,Plattformen för preklinisk PET

Varasteh, Zohreh (author): Uppsala universitet,Plattformen för preklinisk PET

Andersson, Ken (author): KTH,Proteinteknologi

Selvaraju, Ram Kumar (author): Uppsala universitet,Plattformen för preklinisk PET

Altai, Mohamed (author): Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap

Honarvar, Hadis (author): Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap

Strand, Joanna (author): Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap

Stahl, Stefan (author): KTH,Proteinteknologi

Tolmachev, Vladimir (author): Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap

Löfblom, John (author): KTH,Proteinteknologi

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(creator_code:org_t)

2014-03-13
2014
English.
In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 41:7, s. 1450-1459

Related links:: http://uu.diva-porta...; show more...; https://uu.diva-port... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; https://urn.kb.se/re...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Human epidermal growth factor receptor type 3 (HER3) is a transmembrane receptor tyrosine kinase belonging to the HER (ErbB) receptor family. Membranous expression of HER3 is associated with trastuzumab resistance in breast cancer and the transition to androgen independence in prostate cancer. Imaging of HER3 expression in malignant tumors may provide important diagnostic information that can influence patient management. Affibody molecules with low picomolar affinity to HER3 were recently selected. The aim of this study was to investigate the feasibility of HER3 imaging using radiolabeled Affibody molecules. A HER3-binding Affibody molecule, Z(08699), with a HEHEHE-tag on N-terminus was labeled with Tc-99m(CO)(3) using an IsoLink kit. In vitro and in vivo binding specificity and the cellular processing of the labeled binder were evaluated. Biodistribution of Tc-99m(CO)(3)-HEHEHE-Z(08699) was studied over time in mice bearing HER3-expressing xenografts. HEHEHE-Z(08699) was labeled with Tc-99m(CO)(3) with an isolated yield of > 80 % and a purity of > 99 %. Binding of Tc-99m(CO)(3)-HEHEHE-Z(08699) was specific to BT474 and MCF7 (breast cancer), and LS174T (colon cancer) cells. Cellular processing showed rapid binding and relatively quick internalization of the receptor/Affibody molecule complex (70 % of cell-associated radioactivity was internalized after 24 h). The tumor targeting was receptor mediated and the excretion was predominantly renal. Receptor-mediated uptake was also found in the liver, lung, stomach, intestine, and salivary glands. At 4 h pi, tumor-to-blood ratios were 7 +/- 3 for BT474, and 6 +/- 2 for LS174T xenografts. LS174T tumors were visualized by microSPECT 4 h pi. The results of this study suggest the feasibility of HER3-imaging in malignant tumors using Affibody molecules.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

Keyword

HER3
Affibody molecule
Technetium-99m
Molecular imaging
Molecular targeting

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ref (subject category)
art (subject category)

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By the author/editor: Orlova, Anna; Malm, Magdalena; Rosestedt, Maria; Varasteh, Zohreh; Andersson, Ken; Selvaraju, Ram K ...; show more...; Altai, Mohamed; Honarvar, Hadis; Strand, Joanna; Stahl, Stefan; Tolmachev, Vladi ...; Löfblom, John; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmaceutical S ...

Articles in the publication: European Journal ...

By the university: Royal Institute of Technology; Uppsala University

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