Clinical Translation of [68Ga]Ga-NOTA-anti-MMR-sdAb for PET/CT Imaging of Protumorigenic Macrophages.
Purpose: Macrophage mannose receptor (MMR, CD206) expressing tumor-associated macrophages (TAM) are protumorigenic and was reported to negatively impact therapy responsiveness and is associated with higher chances of tumor relapse following multiple treatment regimens in preclinical tumor models. Si...
| Publicado en: | Molecular Imaging & Biology Vol. 21; no. 5; pp. 898 - 907 |
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| Autores principales: | , , , , , , , , , , , , , , |
| Formato: | diagnostic images research tables/charts Journal Article |
| Publicado: |
Springer Nature
Oct2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=138415375&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 138415375 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 15361632 KJU jtl: Molecular Imaging & Biology issn: 15361632 maglogo: N pubinfo: dt: Oct2019 vid: 21 iid: 5 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 138415375 138415375 144034857 NLM30671739 138415375 10.1007/s11307-018-01302-5 NLM30671739 138415375 ppf: 898 ppct: 9 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Clinical Translation of [68Ga]Ga-NOTA-anti-MMR-sdAb for PET/CT Imaging of Protumorigenic Macrophages. aug: au: Xavier, Catarina Blykers, Anneleen Laoui, Damya Bolli, Evangelia Vaneyken, Ilse Bridoux, Jessica Baudhuin, Henri Raes, Geert Everaert, Hendrik Movahedi, Kiavash Van Ginderachter, Jo A. Devoogdt, Nick Caveliers, Vicky Lahoutte, Tony Keyaerts, Marleen affil: In Vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Brussels, Belgium sug: subj: Immunoglobulin Fragments Metabolism Neoplastic Processes Pathology Receptors, Cell Surface Metabolism Macrophages Pathology Heterocyclic Compounds Metabolism Proteins Metabolism Gallium Radioisotopes Metabolism Research, Medical Human Heterocyclic Compounds Radiometry Mice Animal Studies Female Macrophages Metabolism Validation Studies Comparative Studies Evaluation Research Multicenter Studies Clinical Assessment Tools Impact of Events Scale Scales Funding Source Female ab: Purpose: Macrophage mannose receptor (MMR, CD206) expressing tumor-associated macrophages (TAM) are protumorigenic and was reported to negatively impact therapy responsiveness and is associated with higher chances of tumor relapse following multiple treatment regimens in preclinical tumor models. Since the distribution of immune cells within the tumor is often heterogeneous, sampling "errors" using tissue biopsies will occur. In order to overcome this limitation, we propose positron emission tomography (PET)/X-ray computed tomography (CT) imaging using 68Ga-labeled anti-MMR single-domain antibody fragment (sdAb) to assess the presence of these protumorigenic TAM.Procedures: Cross-reactive anti-MMR-sdAb was produced according to good manufacturing practice (GMP) and conjugated to p-SCN-Bn-NOTA bifunctional chelator for 68Ga-labeling. Biodistribution and PET/CT studies were performed in wild-type and MMR-deficient 3LL-R tumor-bearing mice. Biodistribution data obtained in mice were extrapolated to calculate radiation dose estimates for the human adult using OLINDA software. A 7-day repeated dose toxicity study for NOTA-anti-MMR-sdAb was performed in healthy mice up to a dose of 1.68 mg/kg.Results: [68Ga]Ga-NOTA-anti-MMR-sdAb was obtained with 76 ± 2 % radiochemical yield, 99 ± 1 % radiochemical purity, and apparent molar activity of 57 ± 11 GBq/μmol. In vivo biodistribution analysis showed fast clearance via the kidneys and retention in MMR-expressing organs and tumor, with tumor-to-blood and tumor-to-muscle ratios of 6.80 ± 0.62 and 5.47 ± 1.82, respectively. The calculated effective dose was 0.027 mSv/MBq and 0.034 mSv/MBq for male and female, respectively, which means that a proposed dose of 185 MBq in humans would yield a radiation dose of 5.0 and 6.3 mSv to male and female patients, respectively. In the toxicity study, no adverse effects were observed.Conclusions: Preclinical validation of [68Ga]Ga-NOTA-anti-MMR-sdAb showed high specific uptake of this tracer in MMR-expressing TAM and organs, with no observed toxicity. [68Ga]Ga-NOTA-anti-MMR-sdAb is ready for a phase I clinical trial. pubtype: Academic Journal doctype: diagnostic images research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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