Abstract 3258: Imaging HER-2 positive breast cancer tumors with trastuzumab radiolabeled with DOTA, Oxo and PCTA and positron emission tomography (PET)
Bibliographic record
Abstract
Abstract Introduction: Monoclonal antibodies (mAbs) are attractive vectors in the development of diagnostic imaging agents because of their specificity. Labeled with the appropriate radioisotope, mAbs can be used to monitor expression levels of a cell surface receptor non-invasively. The data can be used to stratify or monitor patients for/during targeted chemotherapy therapy. We report here the use of trastuzumab labeled with DOTA, a widely used bifunctional chelate (BFC), and two novel BFCs (Oxo and PCTA), to image HER-2 receptor expression non-invasively in a breast cancer model with PET. Materials and Methods: The BFCs were incubated with trastuzumab in HEPES buffer (50mM, pH 8.5, 20 h), the bioconjugates purified by column chromatography, and radiolabeled with Cu-64 in sodium acetate buffer (40 - 400 MBq, 10 mM, pH 5.5, 0.5 - 2 h). The specificity of the DOTA, Oxo, and PCTA bioconjugates for the HER-2 receptor, and cellular uptake were verified in HER-2 positive cell lines using flow cytometry and scintigraphy, respectively. The PET imaging characteristics and biodistribution of the Cu-64 bioconjugates were examined in HER-2 positive and negative breast cancer tumors grown in mice with the Siemens Inveon Multi-Modality PET-CT animal scanner at 24 and 40h post-injection. Results: The specificity of trastuzumab to the HER-2 receptor was unchanged by conjugation to DOTA, Oxo or PCTA. The range of specific activities (GBq/micromol)of Cu-64 radiolabeled Oxo (49 -100) and PCTA (52-70) were higher than DOTA (46 -47). Radiochemical yields ranged from 23 - 88%, 55- 97% and 50-98% for DOTA, Oxo and PCTA, respectively. In vitro uptake of trastuzumab labeled with Cu-64 by the three BFCs was high in HER-2 positive cells (33 - 44% Cu-64 dose), but negligible in HER-2 negative cells. The tissue biodistribution of all three radiolabeled conjugates were similar; uptake in the HER-2 positive tumors was higher than in the control tumors (p<0.01) as expected at 24 and 40h. However, there was significantly higher uptake of the PCTA and Oxo bioconjugates compared to DOTA (p = 0.014 and p = 0.006, respectively) at the earlier timepoint. The corresponding tumor to background ratios for PCTA and Oxo-trastuzumab were also higher that those for DOTA-trastuzumab. PET images and region of interest analysis show that the Cu-64 labeled bioconjugates of DOTA, Oxo and PCTA accumulate preferentially in HER-2 positive tumors at 24 and 40h. However, visualization of the tumors was clearer with Cu-64 labeled bioconjugates of Oxo and PCTA, compared to DOTA. Conclusions: The novel bifunctional chelates PCTA and Oxo radiolabel Cu-64 more efficiently and rapidly than DOTA under mild conditions. All three radiolabeled conjugates of trastuzumab were specific for the HER-2 receptor in a mouse model for HER-2 positive breast cancer, but the data indicate that tumors can be visualized earlier with Oxo and PCTA. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3258.
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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 | 0.000 | 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".