期刊
BIOCONJUGATE CHEMISTRY
卷 23, 期 6, 页码 1221-1229出版社
AMER CHEMICAL SOC
DOI: 10.1021/bc300039r
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资金
- [NCI ICMIC P50-CA114747]
Positron emission tomography (PET) is an attractive imaging tool to localize and quantify tracer biodistribution. ImmunoPET with an intact mAb typically requires two to four days to achieve optimized tumor-to-normal ratios. Thus, a positron emitter with a half-life of two to four days such as zirconium-89 [Zr-89] (t(1/2): 78.4 h) is ideal. We have developed an antibody-based, long-lived immunoPET tracer Zr-89-Desferrioxamine-p-SCN (Df-Bz-NCS)-rituximab (Zr-iPET) to image tumor for longer durations in a humanized CD20-expressing transgenic mouse model. To optimize the radiolabeling efficiency of Zr-89 with Df-Bz-rituximab, multiple radiolabelings were performed. Radiochemical yield, purity, immunoreactivity, and stability assays were carried out to characterize the Zr-iPET for chemical and biological integrity. This tracer was used to image transgenic mice that express the human CD20 on their B cells (huCD20TM). Each huCD20TM mouse received a 7.4 MBq/dose. One group (n = 3) received a 2 mg/kg predose (blocking) of cold rituximab 2 h prior to Zr-89-iPET; the other group (n = 3) had no predose (nonblocking). Small animal PET/CT was used to image mice at 1, 4, 24, 48, 72, and 120 h. Quality assurance of the Zr-89-iPET demonstrated NCS-Bz-Df: antibody ratio (c/a: 1.5 +/- 0.31), specific activity (0.44-1.64 TBq/mol), radiochemical yield (>70%), and purity (>98%). The Zr-iPET immunoreactivity was >80%. At 120 h, Zr-iPET uptake (% ID/g) as mean +/- STD for blocking and nonblocking groups in spleen was 3.2 +/- 0.1% and 83.3 +/- 2.0% (p value <0.0013.). Liver uptake was 1.32 +/- 0.05% and 0.61 +/- 0.001% (p value <0.0128) for blocking and nonblocking, respectively. The small animal PET/CT image shows the spleen specific uptake of Zr-iPET in mice at 120 h after tracer injection. Compared to the liver, the spleen specific uptake of Zr-iPET is very high due to the expression of huCD20. We optimized the radiolabeling efficiency of Zr-89 with Df-Bz-rituximab. These radioimmunoconjugate lots were stable up to 5 days in serum in vitro. The present study showed that Zr-89 is well-suited for mAbs to image cancer over an extended period of time (up to 5 days).
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