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Affibody-mediated i...
Affibody-mediated imaging of EGFR expression in prostate cancer using radiocobalt-labeled DOTA-Z(EGFR:2377)
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- Mitran, Bogdan (författare)
- Uppsala universitet,Theranostics
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- Andersson, Ken G. (författare)
- KTH,Proteinvetenskap
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- Lindström, Elin (författare)
- Uppsala universitet,Institutionen för läkemedelskemi
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- Garousi, Javad (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Rosestedt, Maria (författare)
- Uppsala universitet,Theranostics
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Ståhl, Stefan (författare)
- KTH,Albanova VinnExcellence Center for Protein Technology, ProNova
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- Orlova, Anna, 1960- (författare)
- Uppsala universitet,Theranostics,Medicinsk strålningsvetenskap,Science for Life Laboratory, SciLifeLab
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- Löfblom, John (författare)
- KTH,Skolan för teknikvetenskap (SCI),Proteinvetenskap
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(creator_code:org_t)
- 2018-10-15
- 2019
- Engelska.
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 41:1, s. 534-542
- Relaterad länk:
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https://www.spandido...
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https://doi.org/10.3...
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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 often overexpressed during prostate cancer (PCa) progression towards androgen-independence after hormone therapy, but the overexpression is lower than in other types of cancers. Despite the low expression, EGFR has emerged as a promising therapeutic target for patients with castration-resistant PCa. Non-invasive methods for determination of EGFR expression in PCa can serve for patient stratification and therapy response monitoring. Radionuclide imaging probes based on affibody molecules (7 kDa) provide high contrast imaging of cancer-associated molecular targets. We hypothesized that the anti-EGFR affibody molecule DOTA-Z(EGFR:2377) labeled with Co-55 (positron-emitter, T1/2=17.5 h) would enable imaging of EGFR expression in PCa xenografts. The human PCa cell line DU-145 was used for in vitro and in vivo experiments and Co-57 was used as a surrogate for Co-55 in the present study. Binding of Co-57-DOTA-Z(EGFR:2377) to EGFR-expressing xenografts was saturable with anti-EGFR monoclonal antibody cetuximab, which would motivate the use of this tracer for monitoring the receptor occupancy during treatment. A significant dose-dependent difference in radioactivity accumulation in tumors and normal organs was observed when the biodistribution was studied 3 h after the injection of 10 and 35 mu g of Co-57-DOTA-Z(EGFR:2377): At lower doses the tumor uptake was 2-fold higher although tumor-to-organ ratios were not altered. For clinically relevant organs for PCa, tumor-to-organ ratios increased with time, and at 24 h pi were 2.2 +/- 0.5 for colon, 7 +/- 2 for muscle, and 4.0 +/- 0.7 for bones. Small animal SPECT/CT images confirmed the capacity of radiocobalt labeled DOTA-Z(EGFR:2377) to visualize EGFR expression in PCa. In conclusion, the present study demonstrated the feasibility of using the radiocobalt labeled anti-EGFR affibody conjugate Z(EGFR:2377) as an imaging agent for in vivo visualization of low EGFR-expressing tumors, like PCa, and for monitoring of receptor occupancy during cetuximab therapy as well as the importance of optimal dosing in order to achieve higher sensitivity molecular imaging.
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 -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
Nyckelord
- prostate cancer
- molecular imaging
- cobalt
- affibody molecule
- HER1
- EGFR
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Mitran, Bogdan
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Andersson, Ken G ...
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Lindström, Elin
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Garousi, Javad
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Rosestedt, Maria
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Tolmachev, Vladi ...
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visa fler...
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Ståhl, Stefan
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Orlova, Anna, 19 ...
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Löfblom, John
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Radiologi och bi ...
- Artiklar i publikationen
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Oncology Reports
- Av lärosätet
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Uppsala universitet
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Kungliga Tekniska Högskolan