Radiolabeling of a polypeptide polymer for intratumoral delivery of alpha-particle emitter, 225Ac, and beta-particle emitter, 177Lu

化学 结合 放射化学 多塔 螯合作用 放射免疫疗法 放射性核素治疗 α粒子 核化学 核医学 抗体 有机化学 单克隆抗体 医学 免疫学 数学分析 物理 数学 原子物理学
作者
Vladimir Shalgunov,Gokce Engudar,Lennart Bohrmann,Luke Wharton,Keiran Maskell,Kerstin Johann,Matthias Barz,Paul Schaffer,Matthias M. Herth,Valery Radchenko
出处
期刊:Nuclear Medicine and Biology [Elsevier BV]
卷期号:104-105: 11-21 被引量:6
标识
DOI:10.1016/j.nucmedbio.2021.11.001
摘要

Radiotherapy of cancer requires both alpha- and beta-particle emitting radionuclides, as these radionuclide types are efficient at destroying different types of tumors. Both classes of radionuclides require a vehicle, such as an antibody or a polymer, to be delivered and retained within the tumor. Polyglutamic acid (pGlu) is a polymer that has proven itself effective as a basis of drug-polymer conjugates in the clinic, while its derivatives have been used for pretargeted tumor imaging in a research setup. trans-Cyclooctene (TCO) modified pGlu is suitable for pretargeted imaging or therapy, as well as for intratumoral radionuclide therapy. In all cases, it becomes indirectly radiolabeled via the bioorthogonal click reaction with the tetrazine (Tz) molecule carrying the radionuclide. In this study, we report the radiolabeling of TCO-modified pGlu with either lutetium-177 (177Lu), a beta-particle emitter, or actinium-225 (225Ac), an alpha-particle emitter, using the click reaction between TCO and Tz.A panel of Tz derivatives containing a metal ion binding chelator (DOTA or macropa) connected to the Tz moiety directly or through a polyethylene glycol (PEG) linker was synthesized and tested for their ability to chelate 177Lu and 225Ac, and click to pGlu-TCO. Radiolabeled 177Lu-pGlu and 225Ac-pGlu were isolated by size exclusion chromatography. The retention of 177Lu or 225Ac by the obtained conjugates was investigated in vitro in human serum.All DOTA-modified Tzs efficiently chelated 177Lu resulting in average radiochemical conversions (RCC) of >75%. Isolated radiochemical yields (RCY) for 177Lu-pGlu prepared from 177Lu-Tzs ranged from 31% to 55%. TLC analyses detected <5% unchelated 177Lu for all 177Lu-pGlu preparations over six days in human serum. For 225Ac chelation, optimized RCCs ranged from 61 ± 34% to quantitative for DOTA-Tzs and were quantitative for the macropa-modified Tz (>98%). Isolated radiochemical yields (RCY) for 225Ac-pGlu prepared from 225Ac-Tzs ranged from 28% to 51%. For 3 out of 5 225Ac-pGlu conjugates prepared from DOTA-Tzs, the amount of unchelated 225Ac stayed below 10% over six days in human serum, while 225Ac-pGlu prepared from macropa-Tz showed a steady release of up to 37% 225Ac.We labeled TCO-modified pGlu polymers with alpha- and beta-emitting radionuclides in acceptable RCYs. All 177Lu-pGlu preparations and some 225Ac-pGlu preparations showed excellent stability in human plasma. Our work shows the potential of pGlu as a vehicle for alpha- and beta-radiotherapy of tumors and demonstrated the usefulness of Tz ligation for indirect radiolabeling.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
刚刚
1秒前
依灵完成签到,获得积分10
1秒前
1秒前
充电宝应助mariawang采纳,获得10
2秒前
王哈哈关注了科研通微信公众号
3秒前
kkdkg发布了新的文献求助10
3秒前
时笙发布了新的文献求助10
3秒前
苏利文完成签到,获得积分10
4秒前
4秒前
小二郎应助尔尔采纳,获得30
4秒前
5秒前
小丑鱼儿发布了新的文献求助10
5秒前
6秒前
Rubby应助Sissi采纳,获得10
6秒前
7秒前
隐形夕阳发布了新的文献求助50
8秒前
搞学术的发布了新的文献求助10
8秒前
Freddie发布了新的文献求助10
10秒前
淡淡梦容发布了新的文献求助10
10秒前
10秒前
mmol发布了新的文献求助10
11秒前
可靠的冰烟完成签到,获得积分10
11秒前
Ava应助kkdkg采纳,获得10
12秒前
Bio应助AA简单男孩采纳,获得26
13秒前
搜集达人应助虚幻靖易采纳,获得10
13秒前
Notdodead应助yyds采纳,获得10
13秒前
科研通AI2S应助Lu采纳,获得10
13秒前
14秒前
14秒前
搞怪的人龙完成签到,获得积分10
15秒前
淡淡梦容完成签到,获得积分10
15秒前
情怀应助star采纳,获得10
16秒前
17秒前
17秒前
19秒前
19秒前
汉堡包应助山河与海采纳,获得10
19秒前
19秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3988732
求助须知:如何正确求助?哪些是违规求助? 3531027
关于积分的说明 11252281
捐赠科研通 3269732
什么是DOI,文献DOI怎么找? 1804764
邀请新用户注册赠送积分活动 881869
科研通“疑难数据库(出版商)”最低求助积分说明 809021