Production of alpha emitters for cancer therapy

6 Sept 2022, 14:40
40m
Aula Leonardi (ECT*)

Aula Leonardi

ECT*

Strada delle Tabarelle 286, I-38123 Villazzano (Trento)
Targeted radionuclide therapy and associated technologies Research on targeted radionuclide therapy and associated technologies

Speaker

Cornelia Hoehr (Life Sciences, TRIUMF Canadian Particle Accelerator and University of Victoria, Canada)

Description

Alpha emitters hold great promise to improve ligandtherapy or Targeted Alpha Therapy (TAT), where an alpha emitter is attached to a biological tracer. The tracer is injected into the blood stream of a cancer patient and accumulates over time in the cells with the targeted expression, e.g.cancer cells. As alpha particles have a relative high Linear Energy Transfer (LET), it typically causes more cell kill than other options for ligandtherapy, e.g.the beta emitter 177Lu. Therefore, alpha emitters can be an excellent therapy choice where high LET is required as a last option due to radiation resistance and whereexternal beam therapy with high LET particles (protons, heavy ions) is not applicable (e.g.widely-spread metastases).

First clinical treatment with the alpha emitter 225Ac have caused large excitement due to successes in hard-to-treat prostate cancer [1]. 225Ac does not only send out one alpha particle, but four in its decay chain. But the supply of 225Ac is limited [2]. At TRIUMF, we have the appropriate accelerator (500 MeV cyclotron) to produce large quantities of 225Ac by proton irradiation of 232Th [3]. We successfully developed the target, the handling, and the purification to produce225Ac. As227Ac is co-produced and constitutes an unwantedcontamination which could accumulate in the bones of patients, potentially causing late side effects or secondary cancer, we also developed the separation of 225Ra. By utilizing the 225Ra as parent isotope and incorporating it into a generator, very pure 225Ac can be produced for curative intent [4, 5].

REFERENCES
[1] C.Kratochwil, F.Bruchertseifer, F.Giesel, M.Weis, F. Verburg, F. Mottaghy, K. Kopka, C.Apostolidis, U.Haberkorn, A. Morgenstern, 225Ac-PSMA-617 for PSMA-targeted a-radiation therapy of metastatic castration-resistant prostate cancer. J. Nucl. Med.57, 1941–1944 (2016).
[2]V. Radchenko, A. Morgenstern, A. Jalilian, C. Ramogida, C. Cutler, C. Duchemin, C. Hoehr,
F. Haddad, F. Buchertseifer, H. Gausemel, H. Yang, J. Osso, K. Washiyama, K. Czherwinski,K. Leufgen, M Pruszynski, O. Valzdorf, P. Causey, P. Schaffer, R. Perron, S. Maxim, S.Wilbur, T. Stora, Y. Li, Production and supply of alpha particles emitting radionuclides for Targeted Alpha Therapy(TAT), J. Nucl. Med.,62 1495 (2021).
[3]V. Radchenko, C. Hoehr, Modern Alchemy to fight Cancer, Nuclear Physics News, 30 28 (2020)
[4]A. Robertson, A. Lobbezoo, L. Moskven, P. Schaffer, C.Hoehr, New target design to produce Ac-225 at TRIUMF, Instruments,3 18 (2019).
[5]a. Robertson, B. McNeil, H. Yang, D.Gendron, R. Perron, V. Radchenko, S. Zeisler, P. Causey,P. Schaffer,232Th-Spallation-Produced 225Ac with Reduced 227Ac Content.Inorg. Chem.59,12156–12165 (2020).

Primary author

Cornelia Hoehr (Life Sciences, TRIUMF Canadian Particle Accelerator and University of Victoria, Canada)

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