Pretargeted Radioimmunotherapy (PRIT™) for Treatment of Non-Hodgkin's Lymphoma (NHL): Initial Phase I/II Study Results
Bibliographic record
Abstract
Pretargeted radioimmunotherapy (PRIT) was investigated in patients with non-Hodgkin's lymphoma (NHL). The PRIT approach used in this study is a multi-step delivery system in which an antibody is used to target streptavidin to a tumor associated antigen receptor, and subsequently biotin is then used to target 90Y radioisotope to the tumor localized streptavidin. A chimeric, IgG1, anti-CD20 antibody, designated C2B8 or Rituximab, was conjugated to streptavidin (SA) and administered to patients with NHL. Thirty-four hours later, a clearing agent, synthetic biotin-N-acetyl-galactosamine, was administered to remove non-localized conjugate from the circulation. Finally, a DOTA-biotin ligand, labeled with 111In for imaging and/or 90Y for therapy was administered. Ten patients with relapsed or refractory NHL were studied. In three patients, the C2B8/SA conjugate was radiolabeled with a trace amount of 186Re in order to assess pharmacokinetics and biodistribution using gamma camera imaging. Seven patients received 30 or 50 mCi/m2 90Y DOTA-biotin. Re-186 C2B8/SA images confirmed that the conjugate localized to known tumor sites and that the clearing agent removed > 95% of the conjugate from the circulation. Radiolabeled biotin localized well to tumor. Unbound radiobiotin was rapidly excreted from the whole body and normal organs. The mean tumor dose calculated was 29 +/- 23 cGy/mCi 90Y and the average whole body dose was 0.76 +/- 0.3 cGy/mCi 90Y, resulting in a mean tumor to whole body dose ratio of 38:1. Only grade I/II non-hematologic toxicity was observed. Hematologic toxicity was also not severe; i.e., five of the seven patients who received 30 or 50 mCi/m2 of 90Y-DOTA-biotin experienced only transient grade III (but no grade IV) hematologic toxicity. Although six of ten patients developed humoral immune responses to the streptavidin, these were delayed and transient and hence may not preclude retreatment. Six of seven patients who received 30 or 50mCi/m2 90Y achieved objective tumor regression, including three complete and one partial response. The estimate of tumor to whole body dose ratio (38:1) achieved with PRIT in these NHL patients is higher than has been achieved in other studies using conventional RIT. Toxicity was mild and tumor response encouraging. PRIT clearly deserves additional study in patients with NHL.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".