Speaker
Prof.
Frank Roesch
(University of Mainz, Germany)
Description
Introduction: Radionuclide generator systems continue to play a key role in providing both diagnostic and therapeutic radionuclides for various applications in nuclear medicine, oncology and interventional cardiology. In parallel to the well established 99Mo/99mTc generator used for SPECT imaging, new generators for PET/CT imaging attract attention. In particular the 68Ge/68Ga system (68Ge: t½ = 270.95 d; 68Ga: t½ = 67.7 min, β+ branching = 89.1%) has found impressive and established clinical application, the 44Ti/44Sc generator (44Ti: t½ = 60 a; 44Sc: t½ = 3.97 h, β+ branching = 94.3) represents a promising system providing a longer-lived daughter, and a 140Nd/140Pr system (140Nd: t½ = 3.37 d d; 140Pr: t½ = 3.39 min, β+ branching = 51.0%) may be used in terms of an in vivo generator.
Challenges: (1) Different to the established 99Mo/99mTc generator used for SPECT imaging, new generators for PET/CT such as the 68Ge/68Ga system [1] and the 44Ti/44Sc generator ask for special generator designs because of the long half-life of the parent nuclide. Both represent secular equilibrium systems (different to the transient 99Mo/99mTc generator) as well as long shelf-life. Both generators may be used over periods of many month and many years, respectively. Still the elution yield of the daughter should be high and the breakthrough of the parent low.
(2) While the generators mentioned all separate parent and daughter nuclides due to different chemical properties of the chemical elements involved, i.e. Mo vs. Tc, Ge vs. Ga, Ti vs. Sc), the 140Nd/140Pr system involves two neighbored lanthanides of very similar chemical behavior.
Experiments and Conclusion: (1) It appears to be a rather general feature of radionuclide generators based on longer-lived parent nuclides, that effective elution modes [2] as well as post-elution processing [3] are mandatory. With those aspects managed in an effective way, the radionuclide generator systems may be tuned to medical systems. This was demonstrated in detail for the 44Ti/44Sc radionuclide generator. Very low breakthrough of 44Ti and high yield of 44Sc is guaranteed by sophisticated generator designs (anion exchange resin as column material, HCl / oxalic acid mixtures for elution), but in addition by a scheme of reverse elution directions. Particular attention was paid to the application of a reverse elution mode, which helps to retain the parent nuclide along the chromatographic column even after many hundred elutions. A 5 mCi generator provides about 170 MBq of 44Sc after direct elution and about 150 MBq following online post-processing similar to the 68Ge/68Ga generator. The final content of 44Ti is as low as < 10 Bq, representing a separation factor of > 107..
(2) With no-carrier-added 140Nd produced by irradiations of CeO2 and Pr2O3 targets [4], an efficient 140Nd/140Pr radionuclide generator system was developed and evaluated. The principle of the radiochemical separation is based on physico-chemical transitions (hot-atom effects) of the daughter 140Pr following the electron decay process of 140Nd. The parent radionuclide 140Nd(III) is quantitatively adsorbed on a solid phase matrix in the form of 140Nd-DOTA-conjugated complexes. 140Nd generated is released from the 140Pr-DOTA core as an ionic species. It is easily separated using low volumes of various aqueous eluents. The elution yield is at least 93%, if an optimized eluent, such as DTPA solution is applied. The system remains stable at least over three half-lives of 140Nd, with high radiolytic stability and low 140Nd breakthrough of ca. 0.025% [5].
[1] Roesch F, Riss PJ. The renaissance of the 68Ge/68Ga radionuclide generator initiates new developments in 68Ga radiopharmaceutical chemistry. Curr Top Med Chem. 10/16 (2010) 1633-68.
[2] Filosofov DV, Loktionova NS, Rösch F. A 44Ti44/Sc radionuclide generator for potential application of 44Sc-based PET-radiopharmaceuticals. Radiochimica Acta 98/3 (2010) 149-156
[3] Pruszyński M, Loktionova NS, Filosofov DV, Rösch F. Post-elution processing of 44Ti/44Sc generator-derived 44Sc for clinical application. Appl Radiat Isot. 68/9 (2010) 1636-1641
[4] Rösch F, Brockmann J, Lebedev NA, Qaim SM. Production and radiochemical separation of the Auger electron emitter 140Nd. Acta Oncologica, 39 (2000) 727-730
[5] Zhernosekov KP, Filosofov DV, Qaim SM, Rösch F. A 140Nd/140Pr radionuclide generator based on physico-chemical transitions in 140Pr complexes after electron capture decay of 140Nd-DOTA. Radiochim Acta 95 (2007) 319-327.
Primary author
Prof.
Frank Roesch
(University of Mainz, Germany)