Production of 43sc radionuclide and radiopharmaceuticals thereof for use in positron emission tomography

Patent metadata

Field	Value
Publication number	US-2017087260-A1
Application number	US-201515310864-A
Country	US
Kind code	A1
Filing date	May 7, 2015
Priority date	May 13, 2014
Publication date	Mar 30, 2017
Grant date	—

Abstract

The radionuclide 43 Sc is produced at commercially significant yields and at specific activities and radionuclidic purities which are suitable for use in radiodiagnostic agents including imaging agents. In a method, a solid target having an isotopically enriched target layer prepared on an inert substrate is positioned in a specially configured target holder and irradiated with a charged-particle beam of protons or deuterons. The beam is generated using an accelerator such as a biomedical cyclotron at energies ranging from 3 to about 22 MeV. The method includes the use of three different nuclear reactions: a) irradiation of enriched 43 Ca targets with protons to generate the radionuclide 43 Scin the nuclear reaction 43 Ca (p,n) 43 Sc, b) irradiation of enriched 42 Ca targets with deuterons to generate the radionuclide 43 Sc in the nuclear reaction 42 Ca(d,n) 43 Sc, and c) irradiation of enriched 46 Ti targets with protons to generate the radionuclide 43 Sc in the nuclear reaction 46 Ti (p,a) 43 Sc.

First claim

1 - 7 . (canceled)

8 . A method for generating 43 Sc, wherein one of the following method steps is applied:
performing a nuclear reaction of 43 Ca(p,n) 43 Sc using enriched 43 Ca at proton beam energies of 5 to 24 MeV; performing a nuclear reaction of 42 Ca(d,n) 43 Sc using enriched 42 Ca and deuteron beam energies of 3 to 12 Mev; or performing a nuclear reaction of 46 Ti(p,α) 43 Sc using enriched 46 Ti and proton beam energies of 10 to 24 MeV.

9 . The method according to claim 8 , which further comprises:
irradiating the enriched 43 Ca target in form of CaCO 3 , Ca (NO 3 ) 2 , CaF 2 or CaO powders of Ca metal having a 43 Ca content of 50% or higher with the proton beam thereby turning the 43 Ca content into the 43 Sc; dissolving an irradiated enriched 43 Ca target in acidic solution and passing a resulting solution through a first column loaded with DGA resin in order to absorb 43 Sc ions; eluting absorbed 43 Sc ions by rinsing the first column with HCl into a second column loaded with a cation exchange resin in order to sorb 43 Sc in the second column; and performing an elution of the 43 Sc from the second column using NH 4 -acetate/HCl or NaCl/HCl.

10 . The method according to claim 8 , which further comprises:
irradiating the enriched 42 Ca target in form of CaCo 3 , Ca(NO 3 ) 2 , CaF 2 , or CaO powders or Ca metal having a 42 Ca content of 50% or higher with \hte deuteron beam thereby turning 42 Ca content into the 43 Sc; dissolving irradiated enriched 42 Ca target in acidic solution and passing a resulting solution through a first column loaded with DGA resin in order to absorb 43 Sc ions; eluting absorbed 43 Sc ions by rinsing the first column with HCl into a second column loaded with a cation exchange resin in order to sorb 43 Sc in the second column; and performing an elution of the 43 Sc from the second column using NH 4 -acetate/HCl or NaCl/HCl.

11 . The method according to claim 9 , which further comprises:
evaporating an effluent from the first column containing an enriched Ca isotope to dryness in order to form a resultant white residue; dissolving the resultant white residue in deionized water and adjusted to a pH of 4.5-5 with ammonia solution and HCl, respectively, in order to form a solution containing solved Ca(II) ions; precipitating a solved content of Ca(II) as Ca-oxalate by adding ammonium oxalate solution; and filtering precipitated Ca-oxalate and transferring an oxalate to a carbonate by slowly heating filtered Ca-oxalate.

12 . The method according to claim 8 , which further comprises:
reducing the enriched 46 Ti target in form of titania powder to Ti metal wherein the titania powder having a content of 46 Ti in a range of 50% or higher is irradiated with the proton beam thereby turning the 46 Ti content into the 43 Sc; dissolving irradiated 46 Ti target in HCl; adding deionized water to dilute solution to 3 to 5 M HCl; and eluting sorbed 43 Sc from SCX column with SCX-Eluent (NaCl/HCl).

13 . The method according to claim 9 , which further comprises selecting the cation exchange resin from the group consisting of DOWEX 50W-X2 cation exchange resin and SCX cation exchange resin.

14 . The method according to claim 10 , which further comprises selecting the cation exchange resin from the group consisting of DOWEX 50W-X2 cation exchange resin and SCX cation exchange resin.

15 . A radiopharmaceutical to be applied in positron emission tomography, comprising:
a radiometal-based radiopharmaceutical agent containing a bifunctional chelator namely a DOTA ligand (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) conjugated to a targeting vector and 43 Sc being bound to a chelating agent.

16 . The radiopharmaceutical according to claim 15 , wherein said targeting vector is selected from the group consisting of an antibody, a peptide, nanoparticles, a vitamine and their derivates.

17 . A radiopharmaceutical, comprising:
a dose for one positron emission tomography having 43 SC to a radio content of 100 to 500 MBq.

18 . The radiopharmaceutical according to claim 17 , wherein said radio content is about 200 MBq.

Assignees

• Scherrer Inst Paul

Inventors

• Tuerler Andreas
• Van Der Meulen Nicholas
• Bunka Maruta

Classifications

• A61K51/0474

  complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group · CPC title

• A61K51/088 Primary

  conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10) · CPC title

• G21G1/10

  by bombardment with electrically charged particles (irradiation devices G21K5/00) · CPC title

• G21G2001/0094

  Other isotopes not provided for in the groups listed above · CPC title

• G21G1/001 Primary

  Recovery of specific isotopes from irradiated targets · CPC title