Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton, Alberta, Canada; and.
J Nucl Med. 2022 Apr;63(4):584-590. doi: 10.2967/jnumed.121.262459. Epub 2021 Aug 12.
Theranostic isotope pairs have gained recent clinical interest because they can be labeled to the same tracer and applied for diagnostic and therapeutic purposes. The goals of this study were to investigate cyclotron production of clinically relevant La activities using natural and isotopically enriched barium target material, compare fundamental PET phantom imaging characteristics of La with those of common PET radionuclides, and demonstrate in vivo preclinical PET tumor imaging using La-PSMA-I&T. La was produced on a 24-MeV cyclotron using an aluminum-indium sealed target with 150-200 mg of isotopically enriched BaCO, BaCO, and Ba metal. A synthesis unit performed barium/lanthanum separation. DOTA, PSMA-I&T, and macropa were radiolabeled with La. Derenzo and National Electrical Manufacturers Association phantom imaging was performed with La, La, and Zr and compared with F, Ga, Sc, and Cu. In vivo preclinical imaging was performed with La-PSMA-I&T on LNCaP tumor-bearing mice. Proton irradiations for 100 µA·min at 23.3 MeV yielded 214 ± 7 MBq of La and 28 ± 1 MBq of La using BaCO, 59 ± 2 MBq of La and 35 ± 1 MBq of La using BaCO, and 81 ± 3 MBq of La and 48 ± 1 MBq of La using Ba metal. At 11.9 MeV, La yields were 81 ± 2 MBq, 6.8 ± 0.4 MBq, and 9.9 ± 0.5 MBq for BaCO, BaCO, and Ba metal. BaCO target material recovery was 95.4% ± 1.7%. National Electrical Manufacturers Association and Derenzo phantom imaging demonstrated that La PET spatial resolution and scanner recovery coefficients were superior to those of Ga and La and comparable to those of Zr. The apparent molar activity was 130 ± 15 GBq/µmol with DOTA, 73 ± 18 GBq/µmol with PSMA-I&T, and 206 ± 31 GBq/µmol with macropa. Preclinical PET imaging with La-PSMA-I&T provided high-resolution tumor visualization with an SUV of 0.97 ± 0.17 at 60 min. With high-yield La cyclotron production, recovery of BaCO target material, and fundamental imaging characteristics superior to those of Ga and La, La represents a promising radiometal candidate to provide high-resolution PET imaging as a PET/α-therapy theranostic pair with Ac or as a PET/Auger electron therapy theranostic pair with La.
治疗性同位素对最近引起了临床关注，因为它们可以用相同的示踪剂标记，并用于诊断和治疗目的。本研究的目的是研究使用天然和同位素富集的钡靶材料在回旋加速器上生产临床相关镧活度，比较镧与常见的正电子发射断层扫描（PET）放射性核素的基本 PET 体模成像特性，并展示使用镧-PSMA-I&T 进行体内临床前 PET 肿瘤成像。使用 24-MeV 回旋加速器，在 150-200mg 同位素富集的 BaCO3、BaCO3 和 Ba 金属的铝-铟密封靶上生产镧。一个合成单元进行钡/镧分离。用镧对 DOTA、PSMA-I&T 和大环肽进行放射性标记。用镧、镧和 Zr 进行 Derenzo 和美国国家电器制造商协会（NEMA）体模成像，并与 F、Ga、Sc 和 Cu 进行比较。使用 La-PSMA-I&T 在 LNCaP 荷瘤小鼠上进行体内临床前成像。在 23.3 MeV 下以 100 µA·min 的质子辐照，使用 BaCO3 获得 214 ± 7 MBq 的 La 和 28 ± 1 MBq 的 La，使用 BaCO3 获得 59 ± 2 MBq 的 La 和 35 ± 1 MBq 的 La，使用 Ba 金属获得 81 ± 3 MBq 的 La 和 48 ± 1 MBq 的 La。在 11.9 MeV 下，对于 BaCO3、BaCO3 和 Ba 金属，La 的产率分别为 81 ± 2 MBq、6.8 ± 0.4 MBq 和 9.9 ± 0.5 MBq。BaCO3 靶材料回收率为 95.4%±1.7%。NEMA 和 Derenzo 体模成像表明，与 Ga 和 La 相比，La PET 的空间分辨率和扫描仪恢复系数更高，与 Zr 相当。用 DOTA 得到的表观摩尔活度为 130 ± 15 GBq/µmol，用 PSMA-I&T 得到的为 73 ± 18 GBq/µmol，用大环肽得到的为 206 ± 31 GBq/µmol。使用 La-PSMA-I&T 进行临床前 PET 成像可提供高分辨率的肿瘤可视化，60 分钟时 SUV 为 0.97 ± 0.17。通过高产率的镧回旋加速器生产、BaCO3 靶材料的回收以及优于 Ga 和 La 的基本成像特性，La 代表一种很有前途的放射性金属候选物，可提供高分辨率的 PET 成像，作为与 Ac 的 PET/α-治疗治疗性对或与 La 的 PET/俄歇电子治疗治疗性对。
