Sökning: id:"swepub:oai:DiVA.org:kth-309573" >
HER3 PET Imaging :
HER3 PET Imaging : 68Ga-Labeled Affibody Molecules Provide Superior HER3 Contrast to 89Zr-Labeled Antibody and Antibody-Fragment-Based Tracers
-
- Rinne, Sara S. (författare)
- Uppsala universitet,Theranostics,KTH Royal Inst Technol, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden
-
- Dahlsson Leitao, Charles (författare)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden
-
- Abouzayed, Ayman (författare)
- Uppsala universitet,Theranostics
-
visa fler...
-
- Vorobyeva, Anzhelika (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
-
- Tolmachev, Vladimir (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Institutionen för medicinska vetenskaper
-
- Ståhl, Stefan (författare)
- KTH,Proteinteknologi
-
- Löfblom, John (författare)
- KTH,Proteinteknologi,KTH Royal Inst Technol, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden
-
- Orlova, Anna (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för läkemedelskemi
-
visa färre...
-
(creator_code:org_t)
- 2021-09-24
- 2021
- Engelska.
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:19, s. 4791-4791
- Relaterad länk:
-
https://doi.org/10.3...
-
visa fler...
-
https://www.mdpi.com...
-
https://uu.diva-port... (primary) (Raw object)
-
https://urn.kb.se/re...
-
https://doi.org/10.3...
-
https://urn.kb.se/re...
-
visa färre...
Abstract
Ämnesord
Stäng
- HER3 (human epidermal growth factor receptor type 3) is a challenging target for diag- nostic radionuclide molecular imaging due to the relatively modest overexpression in tumors and substantial expression in healthy organs. In this study, we compared four HER3-targeting PET tracers based on different types of targeting molecules in a preclinical model: the 89Zr-labeled therapeutic antibody seribantumab, a seribantumab-derived F(ab)2-fragment labeled with 89Zr and 68Ga, and the 68Ga-labeled affibody molecule [68Ga]Ga-ZHER3. The novel conjugates were radiolabeled and characterized in vitro using HER3-expressing BxPC-3 and DU145 human cancer cells. Biodistribu- tion was studied using Balb/c nu/nu mice bearing BxPC-3 xenografts. HER3-negative RAMOS xenografts were used to demonstrate binding specificity in vivo. Autoradiography was conducted on the excised tumors. nanoPET/CT imaging was performed. New conjugates specifically bound to HER3 in vitro and in vivo. [68Ga]Ga-DFO-seribantumab-F(ab’)2 was considered unsuitable for imaging due to the low stability and high uptake in normal organs. The highest tumor-to-non-tumor contrast with [89Zr]Zr-DFO-seribantumab and [89Zr]Zr-DFO-seribantumab-F(ab’)2 was achieved at 96 h and 48 h pi, respectively. Despite lower tumor uptake, [68Ga]Ga-ZHER3 provided the best imaging contrast due to the fastest clearance from blood and normal organs. The results of our study suggest that affibody-based tracers are more suitable for PET imaging of HER3 expression than antibody- and antibody-fragment-based tracers.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (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
- HER3
- PET
- seribantumab
- MM-121
- zirconium-89
- gallium-68
- affibody molecules
- monoclonal antibody
- antibody-fragments
- F(ab’)2
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
-
Cancers
(Sök värdpublikationen i LIBRIS)
Till lärosätets databas