Few PET isotopes are suitable for antibody labelling since immunoPET requires that the PET isotope can be attached to the mAb with high in-vivo stability and the decay half-life of the isotope should match the pharmacokinetics of the mAb (Phelps 2004). Both 124I (t½ = 4.2 d) and 89Zr (t½ = 3.3 d) have a near ideal half-life for anti-body-based imaging, but there are several ad-vantages of using 89Zr over 124I. For 124I, the high energy of its positrons (2.13 MeV), results in a relatively low PET image resolution and the possible dehalogenation in vivo can lead to significant radioactivity uptake in non-targeted organs. In comparison, for 89Zr the low energy of its positron (395.5 keV), results in a PET images with a higher spatial resolution and furthermore, 89Zr is a residualizing isotope, which is trapped inside the target cell after internalization of the mAb. One disadvantage of 89Zr is its abundant high energy gamma-ray (909 keV), which may limit the radioactive dose that can be administered to the patients.
The most popular reaction to produce 89Zr is the 89Y(p,n)89Zr nuclear reaction (Sahar et al., 1966; Link et al., 1986). A proton beam with 14-16MeV energy is used to bombard inexpensive high-purity 89Y metal target (99.9%), avoiding cumbersome recycling of the target material. The yttrium targets could be either a foil (Dejesus and Nickels, 1990), sputtered onto a copper support (Meijs et al., 1994) or Y2O3 pellets (S. A. Kandil, B. Scholten, 2007).
Although 89Zr is currently commercially available, its price is prohibitive for routine clinical applications of 89Zr immuno-PET. The motivation of the present work was the fully automated production of small quantities of 89Zr using commercially available automated systems. We also describe a newly designed and tested platinum cradle, capable of holding a metallic foil and being directly transferable/compatible between the IBA NIRTA target and IBA Pinctada Metal dissolution/purification module.
Material and Methods
The solid target infrastructure used for 89Zr production was identical to the implementation reported earlier for production of 64Cu and 124I (S. Poniger et al. 2012). The commercially avail-able Nirta Solid Target from IBA was coupled to our 18/9 IBA cyclotron using a 2-meter external beam line. A fully automated pneumatic solid target transfer system (STTS) designed by TEMA Sinergie was used to deliver the irradiated tar-gets to a dedicated hotcell. The newly designed platinum cradle holding the yttrium foil (0.127 mm thick, 8 mm d) is shown in FIG. 1.
Typical irradiation parameters were 14.9 MeV at 20 μA for 1.5 hours (90o angle of incidence). The irradiated cradle, containing the 89Zr target is then loaded directly into the IBA Pinctada Metal module (see FIG. 2) for dissolution/purification without disassembly. We used the dissolution/purification method described by Holland et al. 2009, without modification (Purification of 89Zr from 89Y, 88Y and other radionuclidic impurities using a hydroxamate column, with 89Zr eluted with 1.0M Oxalic acid). Radionuclidic purities were evaluated by gamma spectroscopy and traces of metallic impurities were determined by ICP-MS.
Results and Conclusion
FIGURE 3 shows the gamma spectrum of the purified 89Zr solution. Since yttrium has one stable isotope only, relatively pure 89Zr is produced at low energy (14.9 MeV). In these preliminary non-optimized cyclotron productions, average purified 89Zr yield of 0.34 mCi/μAh was achieved, in comparison to values of 1.5 mCi/μAh found in the literature (10° angle of incidence). In these preliminary experiments, no deformation of the foil was observed at 20 μA beam current and higher currents are under investigation.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa.de:bsz:d120-qucosa-166082 |
| Date | 19 May 2015 |
| Creators | Poniger, S., Tochon-Danguy, H., Panopoulos, H., Scott, A. |
| Contributors | Ludwig Institute of Cancer Research, Melbourne branch, Australia,, Helmholtz-Zentrum Dresden - Rossendorf, |
| Publisher | Helmholtz-Zentrum Dresden - Rossendorf |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | doc-type:conferenceObject |
| Format | application/pdf |
| Source | WTTC15 |
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