Shalgunov, Vladimir published the artcileRadiolabeling of a polypeptide polymer for intratumoral delivery of alpha-particle emitter, 225Ac, and beta-particle emitter, 177Lu, Safety of 6,6′-((1,4,10,13-Tetraoxa-7,16-diazacyclooctadecane-7,16-diyl)bis(methylene))dipicolinic acid, the publication is Nuclear Medicine and Biology (2022), 11-21, database is CAplus and MEDLINE.
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) mol. 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 chromatog. 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 radiochem. conversions (RCC) of >75. Isolated radiochem. yields (RCY) for 177Lu-pGlu prepared from 177Lu-Tzs ranged from 31to 55. TLC analyses detected <5unchelated 177Lu for all 177Lu-pGlu preparations over six days in human serum. For 225Ac chelation, optimized RCCs ranged from 61 ± 34to quant. for DOTA-Tzs and were quant. for the macropa-modified Tz (>98). Isolated radiochem. yields (RCY) for 225Ac-pGlu prepared from 225Ac-Tzs ranged from 28to 51. For 3 out of 5 225Ac-pGlu conjugates prepared from DOTA-Tzs, the amount of unchelated 225Ac stayed below 10over six days in human serum, while 225Ac-pGlu prepared from macropa-Tz showed a steady release of up to 37225Ac. 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.
Nuclear Medicine and Biology published new progress about 1128304-86-8. 1128304-86-8 belongs to pyridine-derivatives, auxiliary class Pyridines, name is 6,6′-((1,4,10,13-Tetraoxa-7,16-diazacyclooctadecane-7,16-diyl)bis(methylene))dipicolinic acid, and the molecular formula is C18H12FN, Safety of 6,6′-((1,4,10,13-Tetraoxa-7,16-diazacyclooctadecane-7,16-diyl)bis(methylene))dipicolinic acid.
Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem