Alliot C, Kerdjoudj R, Michel N, Haddad F, Huclier-Markai S
GIP Arronax, 1 rue Arronax, BP 10112, 44817 Saint-Herblain, France; Inserm U892, Centre de Recherche en Cancérologie Nantes - Angers, Institut de Biologie, 9 quai Moncousu, 44035 Nantes cedex 01, France.
Subatech Laboratory, UMR 6457, Ecole des Mines de Nantes, IN2P3/CNRS, Université de Nantes, 4 rue Alfred Kastler, 44300 Nantes, France.
Nucl Med Biol. 2015 Jun;42(6):524-9. doi: 10.1016/j.nucmedbio.2015.03.002. Epub 2015 Mar 11.
Due to its longer half-life, (44)Sc (T1/2 = 3.97 h) as a positron emitter can be an interesting alternative to (68)Ga (T1/2 = 67.71 min). It has been already proposed as a PET radionuclide for scouting bone disease and is already available as a (44)Ti/(44)Sc generator. (44)Sc has an isomeric state, (44 m)Sc (T1/2 = 58.6 h), which can be co-produced with (44)Sc and that has been proved to be considered as an in-vivo PET generator (44 m)Sc/(44)Sc. This work presents the production route of (44 m)Sc/(44)Sc generator from (44)Ca(d,2n), its extraction/purification process and the evaluation of its performances.
Irradiation was performed in a low activity target station using a deuteron beam of 16 MeV, which favors the number of (44 m)Sc atoms produced simultaneously to (44)Sc. Typical irradiation conditions were 60 min at 0.2 μA producing 44 MBq of (44)Sc with a (44)Sc/(44 m)Sc activity ratio of 50 at end of irradiation. Separations of the radionuclides were performed by means of cation exchange chromatography using a DGA® resin (Triskem). Then, the developed process was applied with bigger targets, and could be used for preclinical studies.
The extraction/purification process leads to a radionucleidic purity higher than 99.99% ((43)Sc, (46)Sc, (48)Sc < DL). (44 m)Sc/(44)Sc labeling towards DOTA moiety was performed in order to get an evaluation of the specific activities that could be reached with regard to all metallic impurities from the resulting source. Reaction parameters of radiolabeling were optimized, reaching yields over 95%, and leading to a specific activity of about 10-20 MBq/nmol for DOTA. A recycling process for the enriched (44)Ca target was developed and optimized.
The quality of the final batch with regard to radionucleidic purity, specific activity and metal impurities allowed a right away use for further radiopharmaceutical evaluation. This radionucleidic pair of (44 m)Sc/(44)Sc offers a quite interesting PET radionuclide for being further evaluated as an in-vivo generator.
由于其半衰期较长，（44）Sc（T1/2 = 3.97小时）作为一种正电子发射体，可能是（68）Ga（T1/2 = 67.71分钟）的一个有趣替代物。它已被提议作为一种用于探测骨疾病的PET放射性核素，并且已经有（44）Ti/（44）Sc发生器可供使用。（44）Sc有一种同质异能态，即（44m）Sc（T1/2 = 58.6小时），它可以与（44）Sc共同产生，并且已被证明可被视为一种体内PET发生器（44m）Sc/（44）Sc。本文介绍了通过（44）Ca（d，2n）制备（44m）Sc/（44）Sc发生器的生产路线、其提取/纯化过程以及性能评估。
在一个低活度靶站中使用16 MeV的氘束进行辐照，这有利于同时产生的（44m）Sc原子数量多于（44）Sc。典型的辐照条件是在0.2 μA下辐照60分钟，产生44 MBq的（44）Sc，辐照结束时（44）Sc/（44m）Sc活度比为50。通过使用DGA®树脂（Triskem）的阳离子交换色谱法进行放射性核素的分离。然后，将开发的方法应用于更大的靶材，并可用于临床前研究。
提取/纯化过程导致放射性核素纯度高于99.99%（（43）Sc、（46）Sc、（48）Sc <检测限）。对DOTA部分进行了（44m）Sc/（44）Sc标记，以便评估相对于所得源中所有金属杂质可达到的比活度。对放射性标记的反应参数进行了优化，产率超过95%，导致DOTA的比活度约为10 - 20 MBq/nmol。开发并优化了富集（44）Ca靶材的循环利用过程。
最终批次在放射性核素纯度、比活度和金属杂质方面的质量允许立即用于进一步的放射性药物评估。这种（44m）Sc/（44）Sc放射性核素对作为一种体内发生器提供了一种非常有趣的PET放射性核素，有待进一步评估。
