A5069917402- Radiopharmaceutical Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Peptidase Inhibition and Analysis
- Neuroendocrine Tumor Research Advances
- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Colorectal Cancer Treatments and Studies
- Neuroblastoma Research and Treatments
- Sarcoma Diagnosis and Treatment
- RNA modifications and cancer
- Lymphoma Diagnosis and Treatment
- Galectins and Cancer Biology
University of Saskatchewan
2023-2025
Université Laval
2025
<p>Supplementary Fig. S5: Chemical structure of trastuzumab-antibody-drug radioconjugate (T-ADR). The naked trastuzumab was first conjugated with the drug linker, then p-SCN-Macropa prior to [<sup>225</sup>Ac]Ac-labeling.</p>
<p>Supplementary Fig. S4: Internalization of immunoconjugates into the lysosomes and endosomes. (A) In HCC1954 JIMT-1 cell lines, rapid time-dependent increase in red fluorescence for trastuzumab respective conjugates was observed from 2 hours (h) to 48 hours. Experiments were done triplicate. (B) Representative phase contrast images with constructs</p>
<p>Supplementary Fig. S1: MALDI-TOF- matrix-assisted laser desorption ionization-time of flight mass spectrometry trastuzumab, T-PEG<sub>6</sub>-DM1, and macropa-T-PEG<sub>6</sub>-DM1 was used to determine the drug-to-antibody ratio (DAR) chelator-to-antibody (CAR) for Macropa.</p>
<p>Supplementary Fig. S7: <i>In vitro</i> stability of [<sup>225</sup>Ac]Ac-Macropa-T-PEG<sub>6</sub>-DM1 and radioligand binding assay. (A) Stability was studied in human serum (HS) PBS for up to 10-d duplicate (n = 2). (B) Saturation assay carried out HER2-positive HCC1954 cell line triplicate 3).</p>
<p>Supplementary Fig. S6: Instant thin layer chromatography (left) and radio-SEC-HPLC (right) of [<sup>225</sup>Ac]Ac-Macropa-T-PEG<sub>6</sub>-DM1. The was obtained by collecting fractions the ADR at different time points running them using gamma counter. results were plotted on excel.</p>
<p>Supplementary Fig. S8: H&E staining of some major organs. Micrographs show no microscopic differences between control (saline) and treatment groups. T: trastuzumab; T-PEG<sub>6</sub>-DM1: trastuzumab-PEG<sub>6</sub>-DM1; [<sup>225</sup>Ac]Ac-T-PEG<sub>6</sub>-DM1 = [<sup>225</sup>Ac]Ac-Macropa-trastuzumab-PEG<sub>6</sub>-DM1.</p>
<p>Supplementary Fig. S3: Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) in non-reduced conditions for trastuzumab and its conjugates showing good chemical purity structural integrity of the antibody.</p>
<div>AbstractPurpose:<p>There is overwhelming interest to use actinium-225 ([<sup>225</sup>Ac]Ac) develop targeted α therapies. Antibody–drug conjugates (ADC) are highly cytotoxic. Combining [<sup>225</sup>Ac]Ac with an ADC antibody–drug radioconjugate [<sup>225</sup>Ac]Ac–macropa–trastuzumab(T)–PEG<sub>6</sub>–emtansine (DM1), expected be more effective than its (T–PEG<sub>6</sub>–DM1) against breast...
<p>Supplementary Fig. S2: Size exclusion high performance liquid chromatography (SEC-HPLC) analysis with ultraviolet (uv) detection at 280 nM showing chromatograms of trastuzumab and its conjugates. The confirmed the chemical purity constructs was >95%.</p>
<p>Supplementary Fig. S5: Chemical structure of trastuzumab-antibody-drug radioconjugate (T-ADR). The naked trastuzumab was first conjugated with the drug linker, then p-SCN-Macropa prior to [<sup>225</sup>Ac]Ac-labeling.</p>
<p>Supplementary Fig. S2: Size exclusion high performance liquid chromatography (SEC-HPLC) analysis with ultraviolet (uv) detection at 280 nM showing chromatograms of trastuzumab and its conjugates. The confirmed the chemical purity constructs was >95%.</p>
<p>Supplementary Fig. S7: <i>In vitro</i> stability of [<sup>225</sup>Ac]Ac-Macropa-T-PEG<sub>6</sub>-DM1 and radioligand binding assay. (A) Stability was studied in human serum (HS) PBS for up to 10-d duplicate (n = 2). (B) Saturation assay carried out HER2-positive HCC1954 cell line triplicate 3).</p>
<p>Supplementary Fig. S6: Instant thin layer chromatography (left) and radio-SEC-HPLC (right) of [<sup>225</sup>Ac]Ac-Macropa-T-PEG<sub>6</sub>-DM1. The was obtained by collecting fractions the ADR at different time points running them using gamma counter. results were plotted on excel.</p>
<p>Supplementary Fig. S4: Internalization of immunoconjugates into the lysosomes and endosomes. (A) In HCC1954 JIMT-1 cell lines, rapid time-dependent increase in red fluorescence for trastuzumab respective conjugates was observed from 2 hours (h) to 48 hours. Experiments were done triplicate. (B) Representative phase contrast images with constructs</p>
<p>Supplementary Fig. S3: Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) in non-reduced conditions for trastuzumab and its conjugates showing good chemical purity structural integrity of the antibody.</p>
<p>Supplementary Fig. S8: H&E staining of some major organs. Micrographs show no microscopic differences between control (saline) and treatment groups. T: trastuzumab; T-PEG<sub>6</sub>-DM1: trastuzumab-PEG<sub>6</sub>-DM1; [<sup>225</sup>Ac]Ac-T-PEG<sub>6</sub>-DM1 = [<sup>225</sup>Ac]Ac-Macropa-trastuzumab-PEG<sub>6</sub>-DM1.</p>
<p>Supplementary Fig. S1: MALDI-TOF- matrix-assisted laser desorption ionization-time of flight mass spectrometry trastuzumab, T-PEG<sub>6</sub>-DM1, and macropa-T-PEG<sub>6</sub>-DM1 was used to determine the drug-to-antibody ratio (DAR) chelator-to-antibody (CAR) for Macropa.</p>