First In Vivo and Phantom Imaging of Cyclotron-Produced <sup>133</sup>La as a Theranostic Radionuclide for <sup>225</sup>Ac and <sup>135</sup>La
Bibliographic record
Abstract
Theranostic isotope pairs have gained recent clinical interest as they can be labeled to the same tracer and applied for diagnostic and therapeutic purposes. The goals of this study were to A) investigate cyclotron production of clinically relevant <sup>133</sup>La activities using natural and isotopically enriched barium target material, B) compare fundamental positron emission tomography (PET) phantom imaging characteristics of <sup>133</sup>La with common PET radionuclides, and C) demonstrate in vivo preclinical PET tumor imaging using <sup>133</sup>La-PSMA-I&T. <b>Methods:</b><sup>133</sup>La was produced on a 24 MeV cyclotron using an aluminum-indium sealed target with 150-200 mg of isotopically enriched <sup>135</sup>BaCO<sub>3</sub>, natBaCO<sub>3</sub>, and natBa metal. A NEPTIS Mosaic-LC performed Ba/La separation. DOTA, PSMA-I&T, and macropa were radiolabeled with <sup>133</sup>La. Derenzo and National Electrical Manufacturers Association (NEMA) phantom imaging was performed with <sup>133</sup>La, <sup>132</sup>La, and <sup>89</sup>Zr and compared with <sup>18</sup>F, <sup>68</sup>Ga, <sup>44</sup>Sc, and <sup>64</sup>Cu. In vivo preclinical imaging was performed with <sup>133</sup>La-PSMA-I&T in LNCaP tumor-bearing mice. <b>Results:</b> Proton irradiations for 100 µA·min at 23.3 MeV yielded 214 ± 7 MBq <sup>133</sup>La and 28 ± 1 MBq <sup>135</sup>La using <sup>135</sup>BaCO<sub>3</sub>, 59 ± 2 MBq <sup>133</sup>La and 35 ± 1 MBq <sup>135</sup>La using natBaCO<sub>3</sub> and 81 ± 3 MBq <sup>133</sup>La and 48 ± 1 MBq <sup>135</sup>La using natBa metal. At 11.9 MeV, <sup>135</sup>La yields were: 81 ± 2 MBq, 6.8 ± 0.4 MBq, and 9.9 ± 0.5 MBq for <sup>135</sup>BaCO<sub>3</sub>, natBaCO<sub>3</sub>, and natBa metal. BaCO<sub>3</sub> target material recovery was 95.4 ± 1.7%. NEMA and Derenzo phantom imaging demonstrated <sup>133</sup>La PET spatial resolution, and scanner recovery coefficient were superior compared to <sup>68</sup>Ga, <sup>132</sup>La, and comparable to <sup>89</sup>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 <sup>133</sup>La-PSMA-I&T provided high-resolution tumor visualization with a SUV60min of 0.97 ± 0.17. <b>Conclusion:</b> With high-yield <sup>133</sup>La cyclotron production, recovery of BaCO<sub>3</sub> target material, and superior fundamental imaging characteristics compared to <sup>68</sup>Ga and <sup>132</sup>La, <sup>133</sup>La represents a promising radiometal candidate to provide high-resolution PET imaging as a PET/alpha therapy theranostic pair with <sup>225</sup>Ac, or a PET/Auger electron therapy theranostic pair with <sup>135</sup>La.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".