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Optimization of Radiolabeling of a [ 90 Y]Y-Anti-CD66-Antibody for Radioimmunotherapy before Allogeneic Hematopoietic Cell Transplantation

Cancers, 2023-07, Vol.15 (14), p.3660 [Peer Reviewed Journal]

2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;2023 by the authors. 2023 ;ISSN: 2072-6694 ;EISSN: 2072-6694 ;DOI: 10.3390/cancers15143660 ;PMID: 37509321

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Title:
Optimization of Radiolabeling of a [ 90 Y]Y-Anti-CD66-Antibody for Radioimmunotherapy before Allogeneic Hematopoietic Cell Transplantation
Author: Winter, Gordon ; Hamp-Goldstein, Carmen ; Fischer, Gabriel ; Kletting, Peter ; Glatting, Gerhard ; Solbach, Christoph ; Herrmann, Hendrik ; Sala, Elisa ; Feuring, Michaela ; Döhner, Hartmut ; Beer, Ambros J ; Bunjes, Donald ; Prasad, Vikas
Subjects: Acute lymphoblastic leukemia ; Acute myeloid leukemia ; Adaptation ; Allografts ; anti-CD66 antibody ; Antibodies ; Bone marrow ; Chelating agents ; Chemotherapy ; Chromatography ; Dosimetry ; hematopoietic cell transplantation (HCT) ; Hematopoietic stem cells ; Ions ; Kidneys ; Labeling ; Leukemia ; Liver diseases ; Lymphatic leukemia ; Monoclonal antibodies ; myeloablation ; Myelodysplastic syndrome ; p-SCN-Bn-CHX-A″-DTPA ; Quality control ; Radiation ; Radiation therapy ; radioimmunotherapy ; Remission ; Risk groups ; Sensors ; Stem cell transplantation ; Toxicity ; Transplants & implants ; yttrium-90
Is Part Of: Cancers, 2023-07, Vol.15 (14), p.3660
Description: For patients with acute myeloid leukemia, myelodysplastic syndrome, or acute lymphoblastic leukemia, allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment. In addition to standard conditioning regimens for HCT, high-dose radioimmunotherapy (RIT) offers the unique opportunity to selectively deliver a high dose of radiation to the bone marrow while limiting side effects. Modification of a CD66b-specific monoclonal antibody (mAb) with a DTPA-based chelating agent should improve the absorbed dose distribution during therapy. The stability and radioimmunoreactive fraction of the radiolabeled mAbs were determined. Before RIT, all patients underwent dosimetry to determine absorbed doses to bone marrow, kidneys, liver, and spleen. Scans were performed twenty-four hours after therapy for quality control. A radiochemical purity of >95% and acceptable radioimmunoreactivity was achieved. Absorbed organ doses for the liver and kidney were consequently improved compared to reported historical data. All patients tolerated RIT well with no treatment-related acute adverse events. Complete remission could be observed in 4/5 of the patients 3 months after RIT. Two patients developed delayed liver failure unrelated to the radioimmunotherapy. The improved conjugation and radiolabeling procedure resulted in excellent stability, radiochemical purity, and CD66-specific radioimmunoreactivity of Y-labeled anti-CD66 mAb. RIT followed by conditioning and HCT was well tolerated. Based on these promising initial data, further prospective studies of [ Y]Y-DTPA-Bn-CHX-A″-anti-CD66-mAb-assisted conditioning in HCT are warranted.
Publisher: Switzerland: MDPI AG
Language: English
Identifier: ISSN: 2072-6694
EISSN: 2072-6694
DOI: 10.3390/cancers15143660
PMID: 37509321
Source: DOAJ Directory of Open Access Journals
GFMER Free Medical Journals
PubMed Central
ROAD: Directory of Open Access Scholarly Resources
ProQuest Central

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Optimization of Radiolabeling of a [ 90 Y]Y-Anti-CD66-Antibody for Radioimmunotherapy before Allogeneic Hematopoietic Cell Transplantation

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