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Preparation and eva...
Preparation and evaluation of (68)Ga-DOTA-hEGF for visualisation of EGFR expression in malignant tumours
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- Velikyan, Irina (författare)
- Uppsala universitet,Avdelningen för organisk kemi
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- Liljegren Sundberg, Åsa (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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Lindhe, Örjan (författare)
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visa fler...
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Höglund, A Urban (författare)
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Eriksson, Olof (författare)
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Werner, Eva (författare)
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- Carlsson, Jörgen (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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Bergström, Mats (författare)
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- Långström, Bengt (författare)
- Uppsala universitet,Avdelningen för organisk kemi
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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visa färre...
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(creator_code:org_t)
- 2005
- 2005
- Engelska.
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Ingår i: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 46:11, s. 1881-1888
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- Detection of epidermal growth factor receptor (EGFR) overexpression in many carcinomas provides important diagnostic information, which can influence patient management. The use of PET may enable such detection in vivo by a noninvasive procedure with high sensitivity. The aim of this study was to develop a method for preparation of a positron-emitting tracer based on a natural ligand to EGFR, the recombinant human epidermal growth factor (hEGF), and to perform a preclinical evaluation of the tracer.METHODS: DOTA-hEGF (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) was prepared by coupling of a N-sulfosuccinimide ester of DOTA to hEGF. The conjugate was labeled with a generator-produced positron-emitting nuclide, (68)Ga (half-life = 68 min), using microwave heating. Binding specificity, affinity, internalization, and retention of (68)Ga-DOTA-hEGF was studied in 2 EGFR-expressing cell lines, U343 glioma cells and A431 cervical carcinoma cells. Biodistribution and microPET visualization studies were performed in BALB/c nu/nu mice bearing A431 carcinoma xenografts.RESULTS: A 1-min-long microwave-assisted labeling provided radioactivity incorporation of 77% +/- 4%. Both cell lines demonstrated receptor-specific uptake of the conjugate, rapid internalization of the tracer, and good retention of radioactivity. Binding to both cell lines occurred with high affinity, approximately 2 nmol/L. The biodistribution study demonstrated accumulation of radioactivity in xenografts and in EGFR-expressing organs. The microPET imaging study enabled visualization of tumors and demonstrated quick--within 5 min--localization of radioactivity in tumors.CONCLUSION: (68)Ga-DOTA-hEGF has potential for imaging EGFR overexpression in tumors.
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