Abstract 4883: Peptide-based PET imaging agents using novel bifunctional chelates and 64Cu
Bibliographic record
Abstract
Abstract Introduction: Developing peptide-based PET imaging agents would be highly advantageous due to their high affinity and specificity. Two novel bifunctional chelates (BFC), PCTA and Oxo-DO3A, have previously been used to label antibodies with 64Cu. Complexation of 64Cu with PCTA and Oxo-DO3A was more efficient than with DOTA; the PCTA and OXO-DO3A complexes were also more stable and had more favourable pharmacokinetics[1]. Similarly, PCTA was also found to complex 68Ga more efficiently than DOTA[2]. The utility of PCTA and Oxo-DO3A for radiolabeling peptides specific for tumour angiogenesis processes were further investigated. Methods: The receptor number and affinity of RGD peptides were determined in mouse vascular endothelial cells. Mouse vascular endothelial cells were grown and varying amounts of I-125 echistatin were added to 1 million cells until receptors were saturated. A competitive binding assay, where a set amount of I-125 echistatin was added to the cells in the presence of unlabeled peptides, confirmed the specificity of the peptides for the target. In vivo studies were carried out in HT29 human colorectal tumors grown subcutaneously in RAG2M mice. 64Cu radiolabeled bioconjugates of PCTA, Oxo-DO3A and DOTA were injected with and without excess cyclo-(RGDyK) peptide. The amount of activity in the blood, tumor, liver, kidney and muscle was measured and compared to each of the BFC. Results: The binding assay revealed the saturation of mouse vascular endothelial cells was achieved when 0.8µci of I-125 echistatin was added. The competitive binding assay indicated an IC50 at a concentration of 9pM of DOTA-RGD. In vivo biodistribution studies showed good tumor to blood ratios for all of the 64Cu radiolabeled bioconjugates and better tumor to muscle ratios for the 64Cu radiolabeled bioconjugates of PCTA and Oxo-DO3A. Conclusion: The bifunctional chelates PCTA and Oxo-DO3A were found to be effective for radiolabeling peptides with 64Cu; the resulting complexes appear to be more stable than those of DOTA. The data show that PCTA and Oxo-DO3A radiolabel peptides more efficiently than DOTA, and that the resulting complexes are more stable. Angiogenesis in HT-29 tumours was also imaged successfully using the peptides labeled with PCTA and Oxo-DO3A. References: 1. C.L. Ferreira, D.T.T. Yapp. E. Lamsa, M. Gleave, C. Bensimon, P. Jurek, G.E. Kiefer, Nucl. Med. Biol. 35: 875-882 (2008) 2. C.L. Ferreira, E. Lamsa, M. Woods, Y. Duan, P. Fernando, C. Bensimon, M. Kordos, K. Guenther, P. Jurek, G.E. Kiefer, Bioconj. Chem. 21: 531-536 (2010) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4883. doi:10.1158/1538-7445.AM2011-4883
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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 | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".