Department of Nuclear Medicine and PET, Prince of Wales Hospital, Randwick, Sydney, NSW 2031, Australia.
The Centenary Institute, The University of Sydney, Camperdown, Sydney, NSW 2050, Australia.
Curr Radiopharm. 2022;15(3):184-193. doi: 10.2174/1874471014666211122100646.
4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid (GSAO) when conjugated with a bifunctional chelator 2,2'-(7-(1-carboxy-4-((2,5-dioxopyrrolidin-1-yl)oxy)-4- oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NODAGA) (hereafter referred to as Cell Death Indicator [CDI]), enters dead and dying cells and binds to 90kDa heat shock proteins (hsp90).
This study assesses stability, biodistribution, imaging, and radiation dosimetry of [68Ga]- Ga-CDI for positron emission tomography (PET).
Preparation of [Ga]Ga-CDI was performed as previously described. Product stability and stability in plasma were assessed using high-performance liquid chromatography. Biodistribution and imaging were conducted in ten healthy male Lewis rats at 1 and 2 h following intravenous [Ga]Ga-CDI injection. Human radiation dosimetry was estimated by extrapolation for a standard reference man and calculated with OLINDA/EXM 1.1.
Radiochemical purity of [Ga]Ga-CDI averaged 93.8% in the product and 86.7% in plasma at 4 h post-synthesis. The highest concentration of [Ga]Ga-CDI is observed in the kidneys; [Ga]Ga-CDI is excreted in the urine, and mean retained activity was 32.4% and 21.4% at 1 and 2 h post-injection. Lower concentrations of [Ga]Ga-CDI were present in the small bowel and liver. PET CT was concordant and additionally demonstrated focal growth plate uptake. The effective dose for [Ga]Ga-CDI is 2.16E-02 mSv/MBq, and the urinary bladder wall received the highest dose (1.65E-02 mSv/Mbq).
[Ga] Ga-CDI is stable and has favourable biodistribution, imaging, and radiation dosimetry for imaging of dead and dying cells. Human studies are underway.
4-(N-(谷胱甘酰基乙酰基)氨基)苯胂酸（GSAO）与双功能螯合剂 2,2'-(7-(1-羧基-4-((2,5-二氧代吡咯烷-1-基)氧基)-4-氧代丁基)-1,4,7-三氮杂环壬烷-1,4-二基)二乙酸（NODAGA）（以下简称细胞死亡指示剂[CDI]）偶联后，进入死亡和濒死的细胞，并与 90kDa 热休克蛋白（hsp90）结合。
本研究评估用于正电子发射断层扫描（PET）的[68Ga]-Ga-CDI 的稳定性、生物分布、成像和辐射剂量学。
如前所述进行[Ga]Ga-CDI 的制备。使用高效液相色谱法评估产品稳定性和血浆稳定性。在静脉注射[Ga]Ga-CDI 后 1 和 2 小时，在 10 只健康雄性 Lewis 大鼠中进行生物分布和成像。通过外推标准参考人估算人类辐射剂量，并使用 OLINDA/EXM 1.1 进行计算。
[Ga]Ga-CDI 的放射化学纯度在产物中平均为 93.8%，在合成后 4 小时的血浆中为 86.7%。[Ga]Ga-CDI 的最高浓度出现在肾脏中；[Ga]Ga-CDI 经尿液排泄，注射后 1 和 2 小时的平均滞留活性分别为 32.4%和 21.4%。[Ga]Ga-CDI 的浓度较低见于小肠和肝脏。PET CT 是一致的，并额外显示出焦点生长板摄取。[Ga]Ga-CDI 的有效剂量为 2.16E-02 mSv/MBq，膀胱壁接受的剂量最高（1.65E-02 mSv/Mbq）。
[Ga]Ga-CDI 稳定，具有良好的生物分布、成像和辐射剂量学特性，可用于成像死亡和濒死的细胞。人体研究正在进行中。
