Optimal composition and position of histidine-containing tags improves biodistribution of 99mTc-labeled DARPin G3; Scientific Reports; Vol. 9
| Parent link: | Scientific Reports Vol. 9.— 2019.— [9405, 11 p.] |
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| Beste egile batzuk: | , , , , , , , , , , , |
| Gaia: | Title screen Radionuclide molecular imaging of HER2 expression in disseminated cancer enables stratification of patients for HER2-targeted therapies. DARPin G3, a small (14?kDa) engineered scaffold protein, is a promising probe for imaging of HER2. We hypothesized that position (C- or N-terminus) and composition (hexahistidine or (HE)3) of histidine-containing tags would influence the biodistribution of [99mTc]Tc(CO)3-labeled DARPin G3. To test the hypothesis, G3 variants containing tags at N-terminus (H6-G3 and (HE)3-G3) or at C-terminus (G3-H6 and G3-(HE)3) were labeled with [99mTc]Tc(CO)3. Labeling yield, label stability, specificity and affinity of the binding to HER2, biodistribution and tumor targeting properties of these variants were compared side-by-side. There was no substantial influence of position and composition of the tags on binding of [99mTc]Tc(CO)3-labeled variants to HER2. The specificity of HER2 targeting in vivo was confirmed. The tumor uptake in BALB/c nu/nu mice bearing SKOV3 xenografts was similar for all variants. On the opposite, there was a strong influence of the tags on uptake in normal tissues. The tumor-to-liver ratio for [99mTc]Tc(CO)3-(HE)3-G3 was three-fold higher compared to the hexahistidine-tag containing variants. Overall, [99mTc]Tc(CO)3-(HE)3-G3 variant provided the highest tumor-to-lung, tumor-to-liver, tumor-to-bone and tumor-to-muscle ratios, which should improve sensitivity of HER2 imaging in these common metastatic sites. |
| Hizkuntza: | ingelesa |
| Argitaratua: |
2019
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| Gaiak: | |
| Sarrera elektronikoa: | https://doi.org/10.1038/s41598-019-45795-8 |
| Formatua: | MixedMaterials Baliabide elektronikoa Liburu kapitulua |
| KOHA link: | https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=664818 |
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| 200 | 1 | |a Optimal composition and position of histidine-containing tags improves biodistribution of 99mTc-labeled DARPin G3 |f A. G. Vorobjeva (Vorobyeva), A. A. Shulga, E. V. Konovalova [et al.] | |
| 203 | |a Text |c electronic | ||
| 300 | |a Title screen | ||
| 320 | |a [References: 42 tit.] | ||
| 330 | |a Radionuclide molecular imaging of HER2 expression in disseminated cancer enables stratification of patients for HER2-targeted therapies. DARPin G3, a small (14?kDa) engineered scaffold protein, is a promising probe for imaging of HER2. We hypothesized that position (C- or N-terminus) and composition (hexahistidine or (HE)3) of histidine-containing tags would influence the biodistribution of [99mTc]Tc(CO)3-labeled DARPin G3. To test the hypothesis, G3 variants containing tags at N-terminus (H6-G3 and (HE)3-G3) or at C-terminus (G3-H6 and G3-(HE)3) were labeled with [99mTc]Tc(CO)3. Labeling yield, label stability, specificity and affinity of the binding to HER2, biodistribution and tumor targeting properties of these variants were compared side-by-side. There was no substantial influence of position and composition of the tags on binding of [99mTc]Tc(CO)3-labeled variants to HER2. The specificity of HER2 targeting in vivo was confirmed. The tumor uptake in BALB/c nu/nu mice bearing SKOV3 xenografts was similar for all variants. On the opposite, there was a strong influence of the tags on uptake in normal tissues. The tumor-to-liver ratio for [99mTc]Tc(CO)3-(HE)3-G3 was three-fold higher compared to the hexahistidine-tag containing variants. Overall, [99mTc]Tc(CO)3-(HE)3-G3 variant provided the highest tumor-to-lung, tumor-to-liver, tumor-to-bone and tumor-to-muscle ratios, which should improve sensitivity of HER2 imaging in these common metastatic sites. | ||
| 461 | |t Scientific Reports | ||
| 463 | |t Vol. 9 |v [9405, 11 p.] |d 2019 | ||
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