<i>In vivo</i> quantitative SPECT imaging of actinium-226: feasibility and proof-of-concept
Bibliographic record
Abstract
Abstract Objective . 225 Ac radiopharmaceuticals have tremendous potential for targeted alpha therapy, however, 225 Ac ( t 1/2 = 9.9 d) lacks direct gamma emissions for in vivo imaging. 226 Ac ( t 1/2 = 29.4 h) is a promising element-equivalent matched diagnostic radionuclide for preclinical evaluation of 225 Ac radiopharmaceuticals. 226 Ac has two gamma emissions (158 keV and 230 keV) suitable for SPECT imaging. This work is the first feasibility study for in vivo quantitative 226 Ac SPECT imaging and validation of activity estimation. Approach . 226 Ac was produced at TRIUMF (Vancouver, Canada) with its Isotope Separator and Accelerator (ISAC) facility. [ 226 Ac]Ac 3+ was radiolabelled with the bioconjugate crown-TATE developed for therapeutic targeting of neuroendocrine tumours. Mice with AR42J tumour xenografts were injected with either 2 MBq of [ 226 Ac]Ac-crown-TATE or 4 MBq of free [ 226 Ac]Ac 3+ activity and were scanned at 1, 2.5, 5, and 24 h post injection in a preclinical microSPECT/CT. Quantitative SPECT images were reconstructed from the 158 keV and 230 keV photopeaks with attenuation, background, and scatter corrections. Image-based 226 Ac activity measurements were assessed from volumes of interest within tumours and organs of interest. Imaging data was compared with ex vivo biodistribution measured via gamma counter. Main results . We present, to the best of our knowledge, the first ever in vivo quantitative SPECT images of 226 Ac activity distributions. Time-activity curves derived from SPECT images quantify the in vivo biodistribution of [ 226 Ac]Ac-crown-TATE and free [ 226 Ac]Ac 3+ activity. Image-based activity measurements in the tumours and organs of interest corresponded well with ex vivo biodistribution measurements. Significance . Here in, we established the feasibility of in vivo 226 Ac quantitative SPECT imaging for accurate measurement of actinium biodistribution in a preclinical model. This imaging method could facilitate more efficient development of novel actinium labelled compounds by providing accurate quantitative in vivo pharmacokinetic information essential for estimating toxicities, dosimetry, and therapeutic potency.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".