First preclinical SPECT/CT imaging and biodistribution of [165Er]ErCl3 and [165Er]Er-PSMA-617
Bibliographic record
Abstract
Abstract Background 165Er (t1/2 = 10.4 h, Ex-ray = 47.1 keV (59.4%) and 54.3 keV (14.3%)) is a promising radionuclide suitable for targeted Auger electron therapy of cancer. 165Er can be produced at a relatively low cost, high yield, and high purity using small medical cyclotrons. As a late lanthanide, 165Er is easy to label and can be used as a surrogate for other lanthanides or Ac in proof-of-concept studies. In this report, we explore the radiochemistry, in vitro, and in vivo behavior of [165Er]ErCl3 and [165Er]Er-PSMA-617 to showcase the application of this radionuclide. Particularly, we report the first phantom and preclinical SPECT imaging of this radionuclide leveraging its characteristic X-ray photon emissions. Results The 165Ho(p,n)165Er nuclear reaction using a 13 MeV cyclotron demonstrated production yields of up to 25 ± 5 MBq. µA−1 h−1 at the end of the bombardment. After the purification (4.0 ± 0.5 h) using a sequential combination of cation exchange and extraction chromatography, 4-h irradiation produced up to 1.5 GBq of [165Er]ErCl3. High molar activity [165Er]Er-PSMA-617 was prepared (~ 200 MBq/nmol). [165Er]Er-PSMA-617 showed a LogD7.4 value of -2.34 ± 0.24 meaning high hydrophilicity of the complex as expected. The stability of [165Er]Er-PSMA-617 in saline, human, and mouse serum was studied and showed intact tracer after 12 h in all three cases. [165Er]ErCl3 and [165Er]Er-PSMA-617 were both taken up by LNCaP cells. PSMA-617 has IC50 at nanomolar range for [165Er]Er-PSMA-617 in LNCaP cells. SPECT images with preclinical phantoms showed good uniformity, spatial resolution, and quantitative accuracy. SPECT/CT imaging in LNCaP tumor-bearing mice injected with [165Er]Er-PSMA-617 showed high tumor uptake and quantitative accuracy when comparing the results to ex vivo biodistribution %IA/g values. Mice injected with [165Er]ErCl3 showed uptake in bone structures and excretion through both liver and kidneys. Conclusions This study demonstrated the preclinical use of 165Er for the first time. Using [165Er]ErCl3 and [165Er]Er-PSMA-617 as examples, the radiochemistry, cell, and animal studies showed that 165Er can be used as a tool for evaluating targeted radiopharmaceuticals. The X-ray emission from 165Er can be used for quantitative SPECT imaging in mice.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".