Isolation of actinium-225 for medical purposes

Abstract

A procedure is described for isolation and purification of 225 Ac as a 229 Th daughter decay product using ion exchange. The process includes the following steps: separation of 229 Th from a mixture of 225 Ac and 225 Ra ( 225 Ac precursor) using an anion-exchange resin; separation of 225 Ac and 225 Ra using a cation-exchange resin; purification of 225 Ac to remove inactive impurity cations (primarily Fe) using an anion-exchange resin; final purification of the product on a column with a cation-exchange resin.Monoclonal antibodies and other molecular carriers labeled with α-emitting radionuclides find increasing use in the development of methods for therapy of tumor diseases. With these carriers, radionuclides are delivered directly to the target, separate cell [1][2][3][4][5]. These systems also show promise in therapy of infection diseases [6].The major advantage of α-emitters is that α-particles have extremely short range in biological tissues. High linear energy transfer and short range of α-particles ensure high efficiency of destruction of tumor cells [7].The requirements to an ideal α-emitter are as follows:(1) neither the α-emitter itself, nor its decay products should emit high-energy γ-quanta;(2) the α-emitter half-life should be sufficient for ensuring its isolation and delivery, but not too long to pose hazard to the patient;(3) the chemical properties of the α-emitter should ensure strong binding with various carriers;(4) the α-emitter should be available and cheap.The list of α-emitters potentially suitable for use in radiotherapy is given in Table 1 [7-9].Several methods for producing 225 Ac are known. In particular, 225 Ac can be produced by irradiation of ura-

Overview of the Most Promising Radionuclides for Targeted Alpha Therapy: The “Hopeful Eight”

“…More precisely, after extraction of 229 Th and dissolution in 8 M HNO 3 , a first step using anion exchange resins such as MP1, AG1 × 8 or Dowex 1 × 8 allows the separation of mixtures of 225 Ac and 225 Ra. Isolation of 225 Ac is then performed by a second step, either with a cation exchange column [ 27 ], solid phase extraction chromatography [ 17 ] or a combination of anion and cation exchange resins [ 28 ]. These strategies result in the recovery of 225 Ac in high yields (80–95%) and with high radionuclidic purity for a use in preclinical and clinical trials.…”

Development of 225Ac Radiopharmaceuticals: TRIUMF Perspectives and Experiences

“…This 229 Th now exists in two sources: one at ORNL ( ∼ 5.55 GBq (150 mCi), or ∼ 704 mg) [16] and another (1.7 (46 mCi), or 215 mg) [17] transferred to the Institute for Transuranium Elements (ITU, Karlsruhe, Germany). A third 229 Th source (5.55 GBq (150 mCi), 704 mg) obtained from Russia 233 U stockpiles exists at the Leipunskii Institute for Physics and Power Engineering (IPPE, Obninsk, Russia) [18]. These three sources serve as generators of 225 Ac and its parent 225 Ra ( t 1 / 2 = 14.9 d) and act as the major 225 Ac sources worldwide, producing approximately 26.6 GBq (720 mCi) (ORNL) [19] and 13.1 GBq (350 mCi) (ITU) [17] of 225 Ac annually.…”

“…These three sources serve as generators of 225 Ac and its parent 225 Ra ( t 1 / 2 = 14.9 d) and act as the major 225 Ac sources worldwide, producing approximately 26.6 GBq (720 mCi) (ORNL) [19] and 13.1 GBq (350 mCi) (ITU) [17] of 225 Ac annually. While the IPPE source contains as much 229 Th as the ORNL source, reported values indicate 225 Ac production from this source is sporadic [18, 20]. Overall, the accepted global annual production from 229 Th is 63 GBq (1.7 Ci) [21-25].…”

“…At IPPE, separation of 225 Ac and 225 Ra from 229 Th stock (5.6 BGq, 150 mCi) occurs on an anion exchange column in nitric acid followed by Ra/Ac separation on a cation exchange column in diluted nitric acid [18]. The final 225 Ac fraction is additionally purified with a combination of cation and anion exchange columns.…”

Production and Supply of α-Particle–Emitting Radionuclides for Targeted α-Therapy

“…2), possesses about 215 mg of 229 Th (24), and the Leypunsky Institute for Physics and Power Engineer in the Russian Federation (Supplemental Fig. 3) (25) and ORNL in the United States (26) each possesses 700 mg of 229 Th. An additional source recently became available at Canadian Nuclear Laboratories (Supplemental Fig.…”