101,2019-2036 (2001), which is incorporated herein in its entirety.

Background of the Invention Bi-213 is a decay product of actinium-225 (Ac-225), as shown in Figure 2 on page 2021 of the above-referenced Hassfjell et al. publication. The cumulative dose to a small mass of a functionalized organic resin due to in excess of 20 mCi Ac-225 is substantial and will cause premature generator failure of the resin. Furthermore, the continuous generation of radical species on the resin and in the generator eluate can lead to poor radiochemical labeling yields and poor recovery of radiolabled product.

Currently, published generator technology (see, for example, Section IV in the above-referenced Hassfjell et al. publication on pages 2022-2023) is not adequate to prepare economical material for human use. In such pre- existing technology approaches, limitations in materials and time-consuming steps will result in a loss of 25% to 50% of the Bi-213. Economically, such prior art approaches result in a substantial loss of dose of the desired Bi-213 for patient applications. The present invention provides a novel approach for the need in the art for an alternative and superior Bi-213 generator technology.

Summary of the Invention The present invention relates to a process for the recovery of Bi-213 from a solution comprising Ac-225, Bi- 213, and other decay products of Ac-225 that comprises: (a) passing the solution through an ion exchange column that preferentially captures the Ac-225 and its decay products Fr-221 and At-217 but that does not preferentially capture Bi-213 so that the Bi-213 contained in the solution is eluted from the column thereby forming an eluant solution, which is rich in Bi-213, and capturing the solution containing the Bi-213; (b) promptly eluting the captured Ac-225 from the ion exchange column, forming a reinitialized solution containing that Ac-225; (c) repeating step (a) a plurality of times using previously reinitialized solution that contains the Ac-225 and fresh Bi-213 formed by radioactive decay thereby forming additional captured portions of eluant solution that are rich in Bi-213; and (d) combining the solution portions that are rich in Bi-213.

Detailed Description of the Invention of the Invention The present invention is more specifically directed to a method for constructing and operating an Ac-225/Bi-213 separation system capable of producing 1-150 mCi of Bi-213 suitable for clinical applications. The system is designed to have a lifetime of from about one to about two months, producing material every few hours.

In one embodiment of the present invention, there is a Bi-213 supply system comprising a first container containing Ac-225 in solution; a syringe pump and associated tubing ; a ion exchange column with catch plug; a second reservoir of elution liquid with syringe pump and associated tubing; a product vial; and a third reservoir

for backflush and removal of Ac-225 with associated syringe pump and tubing. The system contains isolated shielding from the radiation exposure and can integrate with clinical radiolabeling applications. Increased efficiency is obtained through localized heating of the solutions and ion exchange column.

The proposed system will pass the Ac-225 solution through the ion exchange column adsorbing the Ac-225 and decay daughters francium-221 (Fr-221) and astatine-217 (At- 217). The resultant pass-through solution will contain a high purity solution of Bi-213 with minimal residual of Ac- 225, Fr-221, and At-217. To minimize radiolytic damage to the ion exchange resin, the Ac-225 will be eluted from the ion exchange resin and reinitialized for use ion-2-4 hours, which represents the optimum recovery period for the decay product, Bi-213. This approach will rapidly produce a Bi- 213 product free of Ac-225 without the associated damage of long-term radiolytic exposure to the ion exchange resin or multiple elution steps associated with the product of concern, Bi-213.

A novel modification can be made to the apparatus by replacing the second ion exchange column with a quartz vile from which external heat is applied to evaporate the eluated Ac-225 to dryness, creating an oxide form. The Ac- 225 oxide can then be dissolved with an acid solution allowing the material to be reinitialized for adsorption onto the 1st ion exchange column.

Description of the Figure The Drawing shows a preferred conceptual design for practice of the present invention. What follows is a description of how the design can be used in such practice : The Ac-225, in radioactive decay equilibrium and dissolved in a solution of 0.1 M-1 M acid (such as HC1 or HNO3), is stored in Al.

Upon initiation, V1, V2, V3, V15, and V17 open.

S1 draws a vacuum, pulling the contents of Al through the first Ac-225 column and the catch column, which adsorbs the Ac-225. A typical ion exchange column or membrane for use is a cation-type ion exchange substrate, such as the DOWEX AGW50 or AGMP-1 resins.

The cross linkage and bead size can be adjusted, as necessary, in manners known to persons of ordinary skill in the art. Heat is applied to increase the kinetics of the adsorption reaction with a temperature range of 50°F - 125°F and a nominal operating temperature of about 98. 6°F being preferred.

V1 shuts and V5 opens.

S1 draws additional fluid from B1 to flush the first Ac- 225 column and remove any residual Bi-213 and all valves then shut.

V22 opens and S1 vents and resets. V22 shuts.

V11, V8, V4, V7, V12, V13, V14, and V17 open.

S1 draws a vacuum, pulling the contents of Cl across the catch column and the first Ac-225 column eluting the Ac- 225 from the first Ac-225 column onto the second Ac-225

column and excess fluid is deposited into F1, where the molarity of the solution in Cl can be adjusted to 7M- 10M, with acids such as HC1, HNO3, or NaI, or an organic acid, such as an acetate-based derivative.

All valves shut.

V22 opens and S1 vents and resets. V22 shuts.

V6, V2, V4, V7, V16 and V17 then open.

S1 draws a vacuum, pulling the contents from D1 across the second Ac-225 column eluting the Ac-225 from the second Ac-225 column and depositing the solution into Al, where the solution is reinitialized for future Bi- 213 extraction when needed by adjusting the molarity of the acid from 0. 1-lOM, with acids such as HC1 or NaI, or an organic such as an acetate-based derivative. Typical ion exchange columns or membranes for use include such anion type ion exchange substrates, such as the DOWEX lx8, EICHROM LN, or TEVA brand resins, where the cross linkage and bead size can be adjusted as necessary.

Heat can be applied to increase the kinetics of the adsorption reaction with a temperature range of 50°F- 125°F and a nominal operating temperature of 98. 6°F being preferred. In this step, it is possible to alternatively have S 1 draw a vacuum, pulling the contents from Cl across the first Ac-225 column and the catch column into a heated catch vessel, in lieu of the second Ac-225 column. The solution is then heated to dryness. S1 draws a vacuum pulling the contents of D1 (e. g., 0. 1M to 1M acid, such as nitric acid) into the heated catch vessel redissolving dried Ac-225. S1 draws a vacuum, pulling the contents of the heated catch

vessel into Al where the solution is reinitialized for future Bi-213 extractions.

All valves shut. V22 opens and S1 vents and resets. V 22 shuts.

V10, V8, V4, V7 V12, V13 V14 and V17 open.

The preceding description has been provided to describe certain preferred embodiments of the present invention and, for that reason, should not be construed in a limiting fashion. The Claims that follow set forth the scope of protection desired.