A kit method for the high level synthesis of [211At]MABG.
meta-[(211)At]Astatobenzylguanidine ([(211)At]MABG), an analogue of meta-iodobenzylguanidine (MIBG) labeled with the alpha-emitter (211)At, targets the norepinephrine transporter. Because MABG has been shown to have excellent characteristics in preclinical studies, it has been considered to be a promising targeted radiotherapeutic for the treatment of tumors such as micrometastatic neuroblastoma that overexpress the norepinephrine transporter. To facilitate clinical evaluation of this agent, a convenient method for the high level synthesis of [(211)At]MABG that is adaptable for kit formulation has been developed. A tin precursor anchored to a solid-support was treated with a methanolic solution of (211)At in the presence of a mixture of H(2)O(2)/HOAc as the oxidant; [(211)At]MABG was isolated by simple solid-phase extraction. By using C-18 solid-phase extraction, the radiochemical yield from 25 batches was 63+/-13%; however, loss of radioactivity during evaporation of the methanolic solution was a problem. This difficulty was avoided by use of a cation exchange resin cartridge for isolation of [(211)At]MABG, which resulted in radiochemical yields of 63+/-9% in a shorter duration of synthesis. The radiochemical purity was more than 90% and no chemical impurity has been detected. The final doses were sterile and apyrogenic. These results demonstrate that [(211)At]MABG can be prepared via a kit method at radioactivity levels anticipated for initiation of clinical studies.
Vaidyanathan
Ganesan
G
Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA. ganesanv@duke.edu
Affleck
Donna J
DJ
Alston
Kevin L
KL
Zhao
Xiao-Guang
XG
Hens
Marc
M
Hunter
Duncan H
DH
Babich
John
J
Zalutsky
Michael R
MR
D019797:3-Iodobenzylguanidine / Q000138:chemical synthesis*; D001246:Astatine / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D002855:Chromatography, Thin Layer; D019791:Guanidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D006207:Half-Life; D007202:Indicators and Reagents; D007553:Isotope Labeling; D011786:Quality Control; D011868:Radioisotopes / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D013056:Spectrophotometry, Ultraviolet; D014001:Tin / Q000737:chemistry
D007202:Indicators and Reagents; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C520658:meta-((211)At)astatobenzylguanidine; D019797:3-Iodobenzylguanidine; D014001:Tin; D019791:Guanidine; D001246:Astatine