Bismuth-213 for Targeted Radionuclide Therapy: From Atom to Bedside

Abstract

In contrast to external high energy photon or proton therapy, targeted radionuclide therapy (TRNT) is a systemic cancer treatment allowing targeted irradiation of a primary tumor and all its metastases, resulting in less collateral damage to normal tissues. The α-emitting radionuclide bismuth-213 (213Bi) has interesting properties and can be considered as a magic bullet for TRNT. The benefits and drawbacks of targeted alpha therapy with 213Bi are discussed in this review, covering the entire chain from radionuclide production to bedside. First, the radionuclide properties and production of 225Ac and its daughter 213Bi are discussed, followed by the fundamental chemical properties of bismuth. Next, an overview of available acyclic and macrocyclic bifunctional chelators for bismuth and general considerations for designing a 213Bi-radiopharmaceutical are provided. Finally, we provide an overview of preclinical and clinical studies involving 213Bi-radiopharmaceuticals, as well as the future perspectives of this promising cancer treatment option.

PSMA-Targeting Radiopharmaceuticals for Prostate Cancer Therapy: Recent Developments and Future Perspectives

“…Finally, terbium-161 is an experimental radiometal that is promising for its application in TRT. 161 Tb emits βparticles, along with Auger and conversion electrons. This particularity of 161 Tb makes it deliver higher radiation doses directly to the cancerous tissue and gives it the ability to cause double-strand DNA damage, which can be more effective in clearing cancerous tissue [120].…”

“…The radiopharmaceutical was tested in PSMA(+) PC-3 PIP tumour-bearing mice, showing the same pharmacokinetic profile as [ 177 Lu]Lu-PSMA-617. Interestingly, [ 161 Tb]Tb-PSMA-617 was found to have an enhanced therapeutic effect on PSMA(+) PC-3 PIP tumours with higher survival times among the mice when compared to its 177 Lu counterpart (65 vs. 36 days). The authors attributed the enhancement of therapy to the 161 Tb properties, as it does not only emit β --particles, but also Auger and conversion electrons, which might increase the absorbed dose and thereby cause damage to the tumours [124].…”

“…213 Bi is a mixed emitter, giving both αand β --particles. Aside from not being a pure α-emitter, it also has the limitation of a relatively short half-life of 45 min, which does not match the typical pharmacokinetic profiles of the majority of PSMA-targeting radiopharmaceuticals [161].…”

A Radionuclide Generator of High-Purity Bi-213 for Instant Labeling

“…The radionuclide, 213 Bi, is considered as one of the promising radionuclides for targeted therapy of cancer [ 1 , 2 ]. Radiopharmaceuticals containing 213 Bi are successfully passing clinical trials for the treatment of leukemia [ 3 ], NHL [ 4 ], carcinoma [ 5 ], neuroendocrine tumor [ 6 ], glioma [ 7 ], and melanoma [ 8 ].…”

“…For the same reason, significantly high activities of 213 Bi are required to achieve a therapeutic effect. Depending on the vector molecules, a possible range of 213 Bi administered dose may vary within 5–10 GBq [ 1 ].…”