Preparation of a Zirconium-89 Labeled Clickable DOTA Complex and Its Antibody Conjugate

Author:

Basuli Falguni1,Vasalatiy Olga1,Shi Jianfeng1,Lane Kelly C.1,Escorcia Freddy E.23ORCID,Swenson Rolf E.1ORCID

Affiliation:

1. Chemistry and Synthesis Center, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA

2. Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA

3. Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA

Abstract

Desferrioxamine B (DFO) is the clinical standard chelator for preparing zirconium-89 labeled antibodies. In the current study, the stabilities of a zirconium-89 labeled panitumumab (PAN; Vectibix®) with three different chelators (DFO, DFO*, and DOTA) were compared. PAN is an anti-HER1/EGFR monoclonal antibody approved by the FDA for the treatment of HER1-expressing colorectal cancers and was used as the model antibody for this study. DFO/DFO* conjugates of PAN were directly radiolabeled with zirconium-89 at room temperature to produce [89Zr]Zr-DFO/DFO*-PAN conjugates following a well-established procedure. A zirconium-89 labeled DOTA-PAN conjugate was prepared by an indirect radiolabeling method. A cyclooctyne-linked DOTA chelator (BCN-DOTA-GA) was first radiolabeled with zirconium-89 at 90 °C under a two-step basic pH adjustment method followed by conjugation with PAN-tetrazene at 37 °C to produce a labeled conjugate, BCN-[89Zr]Zr-DOTA-GA-PAN. High reproducibility of the radiolabeling was observed via this two-step basic pH adjustment. The overall radiochemical yield was 40–50% (n = 12, decay uncorrected) with a radiochemical purity of >95% in 2 h synthesis time. All three conjugates were stable in whole human serum for up to 7 days at 37 °C. The kinetic inertness of the conjugates was assessed against the EDTA challenge. BCN-[89Zr]Zr-DOTA-GA-PAN exhibited excellent inertness followed by [89Zr]Zr-DFO*-PAN. [89Zr]Zr-DFO-PAN displayed the lowest level of inertness.

Funder

Intramural Research Programs of the National Institutes of HealthZIA

Publisher

MDPI AG

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