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

Gordon Winter, Carmen Hamp-Goldstein, Gabriel Fischer, Peter Kletting, Gerhard Glatting, Christoph Solbach, Hendrik Herrmann, Elisa Sala, Michaela Feuring, Hartmut Döhner, Ambros J. Beer, Donald Bunjes, Vikas Prasad

Research output: Contribution to journalArticlepeer-review

Abstract

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 90Y-labeled anti-CD66 mAb. RIT followed by conditioning and HCT was well tolerated. Based on these promising initial data, further prospective studies of [90Y]Y-DTPA-Bn-CHX-A″-anti-CD66-mAb-assisted conditioning in HCT are warranted.

Original languageEnglish
Article number3660
JournalCancers
Volume15
Issue number14
DOIs
StatePublished - Jul 2023

Keywords

  • anti-CD66 antibody
  • hematopoietic cell transplantation (HCT)
  • myeloablation
  • p-SCN-Bn-CHX-A″-DTPA
  • radioimmunotherapy
  • yttrium-90

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