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Feasibility of imag...
Feasibility of imaging of epidermal growth factor receptor expression with ZEGFR:2377 affibody molecule labeled with Tc-99m using a peptide-based cysteine-containing chelator
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- Andersson, Ken G. (författare)
- KTH,Proteinteknologi,KTH Royal Inst Technol, Div Prot Technol, SE-10691 Stockholm, Sweden
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- Oroujeni, Maryam (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap,Vladimir Tolmachev
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- Garousi, Javad (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap,Vladimir Tolmachev
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- Mitran, Bogdan (författare)
- Uppsala universitet,Avdelningen för Molekylär Avbildning,Anna Orlova
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- Ståhl, Stefan (författare)
- KTH,Proteinteknologi,KTH Royal Inst Technol, Div Prot Technol, SE-10691 Stockholm, Sweden
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- Orlova, Anna (författare)
- Uppsala universitet,Avdelningen för Molekylär Avbildning,Anna Orlova
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- Löfblom, John (författare)
- KTH,Proteinteknologi,KTH Royal Inst Technol, Div Prot Technol, SE-10691 Stockholm, Sweden
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap,Vladimir Tolmachev
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(creator_code:org_t)
- 2016-10-05
- 2016
- Engelska.
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Ingår i: International Journal of Oncology. - : SPANDIDOS. - 1019-6439 .- 1791-2423. ; 49:6, s. 2285-2293
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- The epidermal growth factor receptor (EGFR) is overexpressed in a number of malignant tumors and is a molecular target for several specific anticancer antibodies and tyrosine kinase inhibitors. The overexpression of EGFR is a predictive biomarker for response to several therapy regimens. Radionuclide molecular imaging might enable detection of EGFR overexpression by a non-invasive procedure and could be used repeatedly. Affibody molecules are engineered scaffold proteins, which could be selected to have a high affinity and selectivity to predetermined targets. The anti-EGFR ZEGFR:2377 affibody molecule is a potential imaging probe for EGFR detection. The use of the generator-produced radionuclide Tc-99m should facilitate clinical translation of an imaging probe due to its low price, availability and favorable dosimetry of the radionuclide. In the present study, we evaluated feasibility of ZEGFR:2377 labeling with Tc-99m using a peptide-based cysteine-containing chelator expressed at the C-terminus of ZEGFR:2377. The label was stable in vitro under cysteine challenge. In addition, Tc-99m-ZEGFR:2377 was capable of specific binding to EGFR-expressing cells with high affinity (274 pM). Studies in BALB/C nu/nu mice bearing A431 xenografts demonstrated that Tc-99m-ZEGFR:2377 accumulates in tumors in an EGFR-specific manner. The tumor uptake values were 3.6 1 and 2.5 0.4% ID/g at 3 and 24 h after injection, respectively. The corresponding tumor-to-blood ratios were 1.8 0.4 and 8 3. The xenografts were clearly visualized at both time-points. This study demonstrated the potential of Tc-99m-labeled ZEGFR:2377 for imaging of EGFR in vivo.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Other Basic Medicine (hsv//eng)
Nyckelord
- epidermal growth factor receptor
- radionuclide molecular imaging
- affibody molecules
- technetium-99m
- A431
- biodistribution
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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