Leonard F. Mausner

Selection of radionuclides for radioimmunotherapy

Selection criteria for radionuclides to be used in radioimmunotherapy are reviewed. Among the topics covered are half‐life, specific activity, type of emission, and ease of preparation. (AIP)

RADIONUCLIDE DEVELOPMENT AT BNL FOR NUCLEAR MEDICINE THERAPY

Radionuclides with medium energy beta emission and a several day half-life have often been viewed as attractive candidates for radioimmunotherapy. Among the most promising in this category are 47Sc, 67Cu, 153Sm, 188Re, and 199Au. The production of 67Cu, 153Sm, 199Au at BNL is summarized and the development of the latest candidate for this application, 47Sc, is described in detail. We also summarize the development of another important therapeutic radionuclide, 117mSn for bone pain palliation.

Production of no-carrier added 67Cu

Copper-67 has been produced at the BLIP by 68Zn(p, 2p) and 70Zn(p, alpha) reactions with 193 MeV protons and at the HFBR using the 67Zn(n, p) route. The effective cross-sections of natZn(p, 2pxn)61,64,67Cu reactions were measured at 200 MeV and compared with predicted values obtained from semi-empirical formulae given by Silberberg and Tsao. From these cross-sections, the fraction of 64Cu in the final 67Cu preparations was estimated and compared with the experimental values. A procedure has been developed consisting of electrodeposition and ion-exchange for isolation of no-carrier-added radiocopper from a Zn target. The method is adaptable for remote hot cell operation. The overall radiochemical yield of 67Cu and the separation factors from a Zn target and other radionuclides were evaluated. The saturation yield of 67Cu produced by the fast neutron 67Zn(n, p) reaction and the corresponding cross-section were remeasured. Experiments have been initiated to attach 67Cu to monoclonal antibodies for immunotherapy applications.

Radiochemical purification of no-carrier-added scandium-47 for radioimmunotherapy.

A procedure, adaptable to large-scale remote operation, was developed to purify no-carrier-added (NCA) 47Sc from irradiated Ti targets. Methods based on extraction chromatography and cation-exchange chromatography were compared. Results of this comparison led to the development of an optimized procedure based on cation-exchange with Dowex AG 50W-X4 and 47Sc elution with HCl/HF. This method gave 90-97% overall 47Sc recovery, with a Ti separation factor greater than 2.4 x 10(-5), and specific activities > or = 0.9 GBq microgram-1. Use of the 47Sc product, for labeling monoclonal antibodies, resulted in consistent labeling yields of > or = 90%.

A new separation procedure for 67Cu from proton irradiated Zn

Abstract Cu-67 has been produced since 1985 at the Brookhaven Linac Isotope Producer (BLIP) by irradiation of natural Zn targets with 200 MeV protons. Since the electrodeposition method used previously for isolation of Cu was slow (24–48 h) and unreliable for remote operation, a new, faster and more reliable method has been devised. It is based on (1) selective extraction of Cu dithizonate into organic solvent from a 0.5 M HCl solution of the bulk Zn target; (2) back extraction of Cu into aqueous phase; (3) removal of Ga by isopropyl ether treatment; and (4) final purification by anion exchange separation from other trace radiocontaminants. This procedure has been successfully adapted to remote hot cell operation, takes about 5–7 h to complete the processing of a typical BLIP irradiated ZnO target, and has resulted in better deliverable yields and specific activity. The overall 67Cu recovery is about 90% under remote conditions. For several 67Cu production runs with this procedure, the average Zn separation factor was 1.1 × 10−6 and average 67Cu specific activity was 5 mCi/μg.

Half-life of 60Fe

Abstract The half-life of 60Fe has been measured to be T 1 2 = (1.49 ± 0.27) × 10 6 a, significantly longer than the one previous measurement of Roy and Kohman which reported a value of 3 × 105 a uncertain by a factor of 3. The present value was obtained from measurements of specific activity and radioisotope concentration in a material produced by spallation of copper with 191 MeV protons. 60Fe/Fe ratios in the range of 10−8 were measured with the Argonne FN tandem-superconducting linear accelerator system in conjunction with an Enge split-pole spectrograph. The specific activity of 60Fe in Fe was measured through the grow-in of the 1.332 MeV gamma-ray line of the 60Co daughter activity.

Development of a large scale production of 67Cu from 68Zn at the high energy proton accelerator: closing the 68Zn cycle.

A number of research irradiations of (68)Zn was carried out at Brookhaven Linac Isotope Producer aiming to develop a practical approach to produce the radioisotope (67)Cu through the high energy (68)Zn(p,2p)(67)Cu reaction. Disks of enriched zinc were prepared by electrodeposition of (68)Zn on aluminum or titanium substrate and isolated in the aluminum capsule for irradition. Irradiations were carried out with 128, 105 and 92 MeV protons for at least 24h. After irradiation the disk was chemically processed to measure production yield and specific activity of (67)Cu and to reclaim the target material. The recovered (68)Zn was irradiated and processed again. The chemical procedure comprised BioRad cation exchange, Chelex-100 and anion exchange columns. Reduction of the oxidation degree of copper allowed for more efficient Cu/Co/Zn separation on the anion exchange column. No radionuclides other than copper isotopes were detected in the final product. The chemical yield of (67)Cu reached 92-95% under remote handling conditions in a hot box. Production yield of (67)Cu averaged 29.2 μCi/[μA-h×g (68)Zn] (1.08MBq/[μA-h×g (68)Zn]) in 24h irradiations. The best specific activity achieved was 18.6 mCi/μg (688.2 MBq/μg).

New approaches in medical imaging using plastic scintillating detectors

Abstract A small animal imaging camera was built in our laboratory, using-fast plastic scintillating detectors ( τ = 2–4 ns) and position sensitive photomultipliers (Hamamatsu) digitized using flash ADCs. Pinhole collimators were used for 125 I imaging to achieve submillimeter resolution with scintillating plates of 28 mm radius and 1.5 mm thickness. A high resolution PET module was constructed with arrays of 1.0 mm diameter plastic scintillating fibers. The feasibility of high resolution imaging was demonstrated by the study of brain blood flow in a rat using 125 I IMP in single photon detection mode and with 64 Cu PTSM by using PET mode. Construction of single photon and positron emission tomographic imaging systems for small animals and subsequently for human imaging is in progress.

Production of 82Sr by proton irradiation of RbCl

Abstract The production of 82 Sr from proton irradiation of natural RbCl targets has been investigated. Protons of 84-51 MeV from the Brookhaven Linac Isotope Producer have been used to prepare up to 24.2 GBq of 82 Sr per target. Chemical isolation of Sr was accomplished with ion exchange on Chelex 100 with an average recovery of 83%. At shipment the 83 Sr/ 82 Sr ratio was 85 Sr/ 82 Sr ratio was

Separation of carrier-free47Sc from titanium targets

The radiochemical separation of no-carrier-added (NCA)47Sc fromnatTi targets has been studied. Scandium-47, a medium-energy β-emitter, is intended for use with labelled tumor associated monoclonal antibodies for radiotherapy. Several radiochemical methods for the separation of NCA47Sc from macroquantities of titanium and other impurities were tested. Four different procedures based on ion exchange, solvent extraction and extraction chromatography are reported. For each method, parameters such as the distribution coefficient, kinetics and recoveries are reported. The selective separation can be performed rapidly by all methods.