Microfluidic Preparation of a 89Zr-Labeled Trastuzumab Single-Patient Dose
Abstract
(89)Zr-labeled antibodies are being investigated in several clinical trials; however, the time requirement for synthesis of clinical doses can hinder patient throughput because of scheduling difficulties. Additionally, low specific activity due to poor labeling efficiency can require larger amounts of the radiopharmaceutical to be administered, possibly leading to adverse side effects. Here, we describe the design and evaluation of a microfluidic reactor capable of synthesizing a single clinical dose of (89)Zr-labeled antibody. (89)Zr-labeled trastuzumab was chosen for this validation because it is currently being evaluated in clinical trials for imaging human epidermal growth factor receptor 2-positive cancer patients. A microreactor fabricated from polydimethylsiloxane/glass was silanated with trimethoxy(octadecyl) silane to reduce antibody adsorption. Desferrioxamine-p-benzyl-isothiocyanate (DFO-Bz-NCS) was conjugated to trastuzumab in an 8:1 molar ratio following the literature procedures using aseptic techniques. Radiolabeling was performed by pumping (89)Zr-oxalate and DFO-Bz-trastuzumab into the microfluidic reactor at a total rate of 20 μL/min in ratios varying from 1:37 to 1:592 mg:MBq at 37°C to achieve optimal labeli...Continue Reading
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