Influence of Residualizing Properties of the Radiolabel on Radionuclide Molecular Imaging of HER3 Using Affibody Molecules
Abstract
:1. Introduction
2. Results
2.1. Radiolabeling and Stability
2.2. In Vitro Studies
2.3. In Vivo Studies
2.4. Imaging
3. Discussion
4. Materials and Methods
4.1. General Materials and Instruments
4.2. Protein Production
4.3. Radiolabeling and Label Stability
4.4. Binding Specificity and Cellular Processing Assays
4.5. Affinity Measurements Using LigandTracer
4.6. Animal Studies
4.7. Statistical Analysis of the Data
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ADAPT | Albumin-Binding Domain Derived Affinity Protein |
BSA | Bovine Serum Albumin |
CT | Computed Tomography |
DARPin | Designed Ankyrin Repeat Protein |
EDTA | Ethylenediaminetetraacetic Acid |
EGFR | Epidermal Growth Factor Receptor |
HER2 | Human Epidermal Growth Factor Receptor 2 |
HER3 | Human Epidermal Growth Factor Receptor 3 |
iTLC | Instant Thin Layer Chromatography |
NODAGA | 1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane |
PBS | Phosphate-Buffered Saline |
RGB SPECT | Red, Green and Blue Single Photon Emission Computed Tomography |
References
- Hynes, N.E.; MacDonald, G. ErbB receptors and signaling pathways in cancer. Curr. Opin. Cell Biol. 2009, 21, 177–184. [Google Scholar] [CrossRef] [PubMed]
- Mishra, R.; Patel, H.; Alanazi, S.; Yuan, L.; Garrett, J.T. HER3 signaling and targeted therapy in cancer. Oncol. Rev. 2018, 12, 355. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Holbro, T.; Beerli, R.R.; Maurer, F.; Koziczak, M.; Barbas, C.F., 3rd; Hynes, N.E. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc. Natl. Acad. Sci. USA 2003, 100, 8933–8938. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tzahar, E.; Waterman, H.; Chen, X.; Levkowitz, G.; Karunagaran, D.; Lavi, S.; Ratzkin, B.J.; Yarden, Y. A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol. Cell Biol. 1996, 16, 5276–5287. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Koumakpayi, I.H.; Diallo, J.S.; Le Page, C.; Lessard, L.; Gleave, M.; Bégin, L.R.; Mes-Masson, A.M.; Saad, F. Expression and nuclear localization of ErbB3 in prostate cancer. Clin. Cancer Res. 2006, 12, 2730–2737. [Google Scholar] [CrossRef] [Green Version]
- Hayashi, M.; Inokuchi, M.; Takagi, Y.; Yamada, H.; Kojima, K.; Kumagai, J.; Kawano, T.; Sugihara, K. High expression of HER3 is associated with a decreased survival in gastric cancer. Clin. Cancer Res. 2008, 14, 7843–7849. [Google Scholar] [CrossRef] [Green Version]
- Lipton, A.; Goodman, L.; Leitzel, K.; Cook, J.; Sperinde, J.; Haddad, M.; Köstler, W.J.; Huang, W.; Weidler, J.M.; Ali, S.; et al. HER3, p95HER2, and HER2 protein expression levels define multiple subtypes of HER2-positive metastatic breast cancer. Breast Cancer Res. Treat. 2013, 141, 43–53. [Google Scholar] [CrossRef] [Green Version]
- Liles, J.S.; Arnoletti, J.P.; Tzeng, C.W.; Howard, J.H.; Kossenkov, A.V.; Kulesza, P.; Heslin, M.J.; Frolov, A. ErbB3 expression promotes tumorigenesis in pancreatic adenocarcinoma. Cancer Biol. Ther. 2010, 10, 555–563. [Google Scholar] [CrossRef] [Green Version]
- Siegfried, J.M.; Lin, Y.; Diergaarde, B.; Lin, H.M.; Dacic, S.; Pennathur, A.; Weissfeld, J.L.; Romkes, M.; Nukui, T.; Stabile, L.P. Expression of PAM50 genes in lung cancer: Evidence that interactions between hormone receptors and HER2/HER3 contribute to poor outcome. Neoplasia 2015, 17, 817–825. [Google Scholar] [CrossRef] [Green Version]
- Tanner, B.; Hasenclever, D.; Stern, K.; Schormann, W.; Bezler, M.; Hermes, M.; Brulport, M.; Bauer, A.; Schiffer, I.B.; Gebhard, S.; et al. ErbB-3 predicts survival in ovarian cancer. J. Clin. Oncol. 2006, 24, 4317–4323. [Google Scholar] [CrossRef] [Green Version]
- Chakrabarty, A.; Sánchez, V.; Kuba, M.G.; Rinehart, C.; Arteaga, C.L. Feedback upregulation of HER3 (ErbB3) expression and activity attenuates antitumor effect of PI3K inhibitors. Proc. Natl. Acad. Sci. USA 2012, 109, 2718–2723. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Engelman, J.A.; Zejnullahu, K.; Mitsudomi, T.; Song, Y.; Hyland, C.; Park, J.O.; Lindeman, N.; Gale, C.M.; Zhao, X.; Christensen, J.; et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007, 316, 1039–1043. [Google Scholar] [CrossRef] [PubMed]
- Jacob, W.; James, I.; Hasmann, M.; Weisser, M. Clinical development of HER3-targeting monoclonal antibodies: Perils and progress. Cancer Treat. Rev. 2018, 68, 111–123. [Google Scholar] [CrossRef] [PubMed]
- Kol, A.; Terwisscha van Scheltinga, A.G.T.; Timmer-Bosscha, H.; Lamberts, L.E.; Bensch, F.; de Vries, E.G.E.; Schröder, C.P. HER3, serious partner in crime: Therapeutic approaches and potential biomarkers for effect of HER3-targeting. Pharmacol. Ther. 2014, 143, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Curley, M.D.; Sabnis, G.J.; Wille, L.; Adiwijaya, B.S.; Garcia, G.; Moyo, V.; Kazi, A.A.; Brodie, A.; MacBeath, G. Seribantumab, an anti-ERBB3 antibody, delays the onset of resistance and restores sensitivity to letrozole in an estrogen receptor-positive breast cancer model. Mol. Cancer Ther. 2015, 14, 2642–2652. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sequist, L.V.; Gray, J.E.; Harb, W.A.; Lopez-Chavez, A.; Doebele, R.C.; Modiano, M.R.; Jackman, D.M.; Baggstrom, M.Q.; Atmaca, A.; Felip, E.; et al. Randomized phase II trial of seribantumab in combination with erlotinib in patients with EGFR wild-type non-small cell lung cancer. Oncologist 2019, 24, 1095–1102. [Google Scholar] [CrossRef] [Green Version]
- Orlova, A.; Bass, T.Z.; Rinne, S.S.; Leitao, C.D.; Rosestedt, M.; Atterby, C.; Gudmundsdotter, L.; Frejd, F.Y.; Löfblom, J.; Tolmachev, V.; et al. Evaluation of the therapeutic potential of a HER3-binding affibody construct TAM-HER3 in comparison with a monoclonal antibody, seribantumab. Mol. Pharm. 2018, 15, 3394–3403. [Google Scholar] [CrossRef]
- Schardt, J.S.; Noonan-Shueh, M.; Oubaid, J.M.; Pottash, A.E.; Williams, S.C.; Hussain, A.; Lapidus, R.S.; Lipkowtiz, S.; Jay, S.M. HER3-targeted affibodies with optimized formats reduce ovarian cancer progression in a mouse xenograft model. AAPS J. 2019, 21, 48. [Google Scholar] [CrossRef]
- Yonesaka, K.; Takegawa, N.; Watanabe, S.; Haratani, K.; Kawakami, H.; Sakai, K.; Chiba, Y.; Maeda, N.; Kagari, T.; Hirotani, K.; et al. An HER3-targeting antibody-drug conjugate incorporating a DNA topoisomerase I inhibitor U3-1402 conquers EGFR tyrosine kinase inhibitor-resistant NSCLC. Oncogene 2019, 38, 1398–1409. [Google Scholar] [CrossRef]
- Schoeberl, B.; Kudla, A.; Masson, K.; Kalra, A.; Curley, M.; Finn, G.; Pace, E.; Harms, B.; Kim, J.; Kearns, J.; et al. Systems biology driving drug development: From design to the clinical testing of the anti-ErbB3 antibody seribantumab (MM-121). NPJ Syst. Biol. Appl. 2017, 3, 16034. [Google Scholar] [CrossRef]
- Henry, K.E.; Ulaner, G.A.; Lewis, J.S. Clinical potential of human epidermal growth factor receptor 2 and human epidermal growth factor receptor 3 imaging in breast cancer. PET Clin. 2018, 13, 423–435. [Google Scholar] [CrossRef] [PubMed]
- Pool, M.; Kol, A.; de Jong, S.; de Vries, E.G.E.; Lub-de Hooge, M.N.; Terwisscha van Scheltinga, A.G.T. 89Zr-mAb3481 PET for HER3 tumor status assessment during lapatinib treatment. mAbs 2017, 9, 1370–1378. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Terwisscha van Scheltinga, A.G.T.; Lub-de Hooge, M.N.; Abiraj, K.; Schröder, C.P.; Pot, L.; Bossenmaier, B.; Thomas, M.; Hölzlwimmer, G.; Friess, T.; Kosterink, J.G.W.; et al. ImmunoPET and biodistribution with human epidermal growth factor receptor 3 targeting antibody 89Zr-RG7116. mAbs 2014, 6, 1051–1058. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lockhart, A.C.; Liu, Y.; Dehdashti, F.; Laforest, R.; Picus, J.; Frye, J.; Trull, L.; Belanger, S.; Desai, M.; Mahmood, S.; et al. Phase 1 evaluation of (64)Cu-DOTA-patritumab to assess dosimetry, apparent receptor occupancy, and safety in subjects with advanced solid tumors. Mol. Imaging Biol. 2016, 18, 446–453. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bensch, F.; Lamberts, L.E.; Smeenk, M.M.; Jorritsma-Smit, A.; Lub-de Hooge, M.N.; Terwisscha van Scheltinga, A.G.T.; de Jong, J.R.; Gietema, J.A.; Schröder, C.P.; Thomas, M.; et al. Zr-lumretuzumab PET imaging before and during HER3 antibody lumretuzumab treatment in patients with solid tumors. Clin. Cancer Res. 2017, 23, 6128–6137. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Menke-van der Houven van Oordt, C.W.; McGeoch, A.; Bergstrom, M.; McSherry, I.; Smith, D.A.; Cleveland, M.; Al-Azzam, W.; Chen, L.; Verheul, H.; Hoekstra, O.S.; et al. Immuno-PET imaging to assess target engagement: Experience from 89Zr-anti-HER3 mAb (GSK2849330) in patients with solid tumors. J. Nucl. Med. 2019, 60, 902–909. [Google Scholar] [CrossRef] [Green Version]
- Wehrenberg-Klee, E.; Turker, N.S.; Heidari, P.; Larimer, B.; Juric, D.; Baselga, J.; Scaltriti, M.; Mahmood, U. Differential receptor tyrosine kinase PET imaging for therapeutic guidance. J. Nucl. Med. 2016, 57, 1413–1419. [Google Scholar] [CrossRef] [Green Version]
- Warnders, F.J.; Terwisscha van Scheltinga, A.G.T.; Knuehl, C.; van Roy, M.; de Vries, E.F.J.; Kosterink, J.G.W.; de Vries, E.G.E.; Lub-de Hooge, M.N. Human epidermal growth factor receptor 3-specific tumor uptake and biodistribution of 89Zr-MSB0010853 visualized by real-time and noninvasive PET imaging. J. Nucl. Med. 2017, 58, 1210–1215. [Google Scholar] [CrossRef] [Green Version]
- Larimer, B.M.; Phelan, N.; Wehrenberg-Klee, E.; Mahmood, U. Phage display selection, in vitro characterization, and correlative PET imaging of a novel HER3 peptide. Mol. Imaging Biol. 2018, 20, 300–308. [Google Scholar] [CrossRef]
- Orlova, A.; Malm, M.; Rosestedt, M.; Varasteh, Z.; Andersson, K.; Selvaraju, R.K.; Altai, M.; Honarvar, H.; Strand, J.; Ståhl, S.; et al. Imaging of HER3-expressing xenografts in mice using a (99m)Tc(CO) 3-HEHEHE-Z HER3:08699 affibody molecule. Eur. J. Nucl. Med. Mol. Imaging 2014, 41, 1450–1459. [Google Scholar] [CrossRef] [Green Version]
- Rosestedt, M.; Andersson, K.G.; Mitran, B.; Tolmachev, V.; Löfblom, J.; Orlova, A.; Ståhl, S. Affibody-mediated PET imaging of HER3 expression in malignant tumours. Sci. Rep. 2015, 5, 15226. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Da Pieve, C.; Allott, L.; Martins, C.D.; Vardon, A.; Ciobota, D.M.; Kramer-Marek, G.; Smith, G. Efficient [18F]AlF Radiolabeling of ZHER3:8698 Affibody Molecule for Imaging of HER3 Positive Tumors. Bioconjug. Chem. 2016, 27, 1839–1849. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rinne, S.S.; Dahlsson Leitao, C.; Mitran, B.; Bass, T.Z.; Andersson, K.G.; Tolmachev, V.; Ståhl, S.; Löfblom, J.; Orlova, A. Optimization of HER3 expression imaging using affibody molecules: Influence of chelator for labeling with indium-111. Sci. Rep. 2019, 9, 655. [Google Scholar] [CrossRef] [Green Version]
- Dahlsson Leitao, C.; Rinne, S.S.; Mitran, B.; Vorobyeva, A.; Andersson, K.G.; Tolmachev, V.; Ståhl, S.; Löfblom, J.; Orlova, A. Molecular design of HER3-targeting affibody molecules: Influence of chelator and presence of HEHEHE-tag on biodistribution of 68Ga-labeled tracers. Int. J. Mol. Sci. 2019, 20, 1080. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rinne, S.S.; Dahlsson Leitao, C.; Gentry, J.; Mitran, B.; Abouzayed, A.; Tolmachev, V.; Ståhl, S.; Löfblom, J.; Orlova, A. Increase in negative charge of 68Ga/chelator complex reduces unspecific hepatic uptake but does not improve imaging properties of HER3-targeting affibody molecules. Sci. Rep. 2019, 9, 17710. [Google Scholar] [CrossRef] [PubMed]
- Prigent, S.A.; Lemoine, N.R.; Hughes, C.M.; Plowman, G.D.; Selden, C.; Gullick, W.J. Expression of the c-erbB-3 protein in normal human adult and fetal tissues. Oncogene 1992, 7, 1273–1278. [Google Scholar] [PubMed]
- Ståhl, S.; Gräslund, T.; Eriksson Karlström, A.; Frejd, F.Y.; Nygren, P.Å.; Löfblom, J. Affibody molecules in biotechnological and medical applications. Trends Biotechnol. 2017, 35, 691–712. [Google Scholar] [CrossRef]
- Fu, R.; Carroll, L.; Yahioglu, G.; Aboagye, E.O.; Miller, P.W. Antibody fragment and affibody immunoPET imaging agents: Radiolabelling strategies and applications. ChemMedChem. 2018, 13, 2466–2478. [Google Scholar] [CrossRef]
- Sörensen, J.; Velikyan, I.; Sandberg, D.; Wennborg, A.; Feldwisch, J.; Tolmachev, V.; Orlova, A.; Sandström, M.; Lubberink, M.; Olofsson, H.; et al. Measuring HER2-receptor expression in metastatic breast cancer using [68Ga]ABY-025 affibody PET/CT. Theranostics 2016, 6, 262–271. [Google Scholar] [CrossRef]
- Malm, M.; Kronqvist, N.; Lindberg, H.; Gudmundsdotter, L.; Bass, T.; Frejd, F.Y.; Höidén-Guthenberg, I.; Varasteh, Z.; Orlova, A.; Tolmachev, V.; et al. Inhibiting HER3-mediated tumor cell growth with affibody molecules engineered to low picomolar affinity by position-directed error-prone PCR-like diversification. PLoS ONE 2013, 8, e62791. [Google Scholar] [CrossRef]
- Rosestedt, M.; Andersson, K.G.; Rinne, S.S.; Leitao, C.D.; Mitran, B.; Vorobyeva, A.; Ståhl, S.; Löfblom, J.; Tolmachev, V.; Orlova, A. Improved contrast of affibody-mediated imaging of HER3 expression in mouse xenograft model through co-injection of a trivalent affibody for in vivo blocking of hepatic uptake. Sci. Rep. 2019, 9, 6779. [Google Scholar] [CrossRef] [PubMed]
- Lindbo, S.; Garousi, J.; Mitran, B.; Altai, M.; Buijs, J.; Orlova, A.; Hober, S.; Tolmachev, V. Radionuclide tumor targeting using ADAPT scaffold proteins: Aspects of label positioning and residualizing properties of the label. J. Nucl. Med. 2018, 59, 93–99. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Deyev, S.; Vorobyeva, A.; Schulga, A.; Proshkina, G.; Güler, R.; Löfblom, J.; Mitran, B.; Garousi, J.; Altai, M.; Buijs, J.; et al. Comparative evaluation of two DARPin variants: Effect of affinity, size, and label on tumor targeting properties. Mol. Pharm. 2019, 3, 995–1008. [Google Scholar] [CrossRef] [PubMed]
- Deyev, S.M.; Vorobyeva, A.; Schulga, A.; Abouzayed, A.; Günther, T.; Garousi, J.; Konovalova, E.; Ding, H.; Gräslund, T.; Orlova, A.; et al. Effect of a radiolabel biochemical nature on tumor-targeting properties of EpCAM-binding engineered scaffold protein DARPin Ec1. Int. J. Biol. Macromol. 2020, 145, 216–225. [Google Scholar] [CrossRef] [PubMed]
- Orlova, A.; Nilsson, F.Y.; Wikman, M.; Widström, C.; Ståhl, S.; Carlsson, J.; Tolmachev, V. Comparative in vivo evaluation of technetium and iodine labels on an anti-HER2 affibody for single-photon imaging of HER2 expression in tumors. J. Nucl. Med. 2006, 47, 512–519. [Google Scholar]
- Malmberg, J.; Sandström, M.; Wester, K.; Tolmachev, V.; Orlova, A. Comparative biodistribution of imaging agents for in vivo molecular profiling of disseminated prostate cancer in mice bearing prostate cancer xenografts: Focus on 111In- and 125I-labeled anti-HER2 humanized monoclonal trastuzumab and ABY-025 affibody. Nucl. Med. Biol. 2011, 38, 1093–1102. [Google Scholar] [CrossRef]
- Tolmachev, V.; Tran, T.A.; Rosik, D.; Sjöberg, A.; Abrahmsén, L.; Orlova, A. Tumor targeting using affibody molecules: Interplay of affinity, target expression level, and binding site composition. J. Nucl. Med. 2012, 53, 953–960. [Google Scholar] [CrossRef] [Green Version]
- Vorobyeva, A.; Schulga, A.; Rinne, S.S.; Günther, T.; Orlova, A.; Deyev, S.; Tolmachev, V. Indirect radioiodination of DARPin G3 using N-succinimidyl-para-iodobenzoate improves the contrast of HER2 molecular imaging. Int. J. Mol. Sci. 2019, 20, 3047. [Google Scholar] [CrossRef] [Green Version]
- Steffen, A.C.; Wikman, M.; Tolmachev, V.; Adams, G.P.; Nilsson, F.Y.; Ståhl, S.; Carlsson, J. In vitro characterization of a bivalent anti-HER-2 affibody with potential for radionuclide-based diagnostics. Cancer Biother. Radiopharm. 2005, 20, 239–248. [Google Scholar] [CrossRef]
- Wållberg, H.; Orlova, A. Slow internalization of anti-HER2 synthetic affibody monomer 111In-DOTA-ZHER2:342-pep2: Implications for development of labeled tracers. Cancer Biother. Radiopharm. 2008, 23, 435–442. [Google Scholar] [CrossRef]
- Tolmachev, V.; Orlova, A.; Andersson, K. Methods for radiolabelling of monoclonal antibodies. Methods Mol. Biol. 2014, 1060, 309–330. [Google Scholar] [PubMed] [Green Version]
- Krasniqi, A.; D’Huyvetter, M.; Devoogdt, N.; Frejd, F.Y.; Sörensen, J.; Orlova, A.; Keyaerts, M.; Tolmachev, V. Same-day imaging using small proteins: Clinical experience and translational prospects in oncology. J. Nucl. Med. 2018, 59, 885–891. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tolmachev, V.; Rosik, D.; Wållberg, H.; Sjöberg, A.; Sandström, M.; Hansson, M.; Wennborg, A.; Orlova, A. Imaging of EGFR expression in murine xenografts using site-specifically labelled anti-EGFR 111In-DOTA-Z EGFR:2377 Affibody molecule: Aspect of the injected tracer amount. Eur. J. Nucl. Med. Mol. Imaging 2010, 37, 613–622. [Google Scholar] [CrossRef] [PubMed]
- Garousi, J.; Andersson, K.G.; Dam, J.H.; Olsen, B.B.; Mitran, B.; Orlova, A.; Buijs, J.; Ståhl, S.; Löfblom, J.; Thisgaard, H.; et al. The use of radiocobalt as a label improves imaging of EGFR using DOTA-conjugated Affibody molecule. Sci. Rep. 2017, 7, 5961. [Google Scholar] [CrossRef] [PubMed]
- Tolmachev, V.; Mume, E.; Sjöberg, S.; Frejd, F.Y.; Orlova, A. Influence of valency and labelling chemistry on in vivo targeting using radioiodinated HER2-binding Affibody molecules. Eur. J. Nucl. Med. Mol. Imaging 2009, 36, 692–701. [Google Scholar] [CrossRef]
- Vorobyeva, A.; Schulga, A.; Konovalova, E.; Güler, R.; Mitran, B.; Garousi, J.; Rinne, S.S.; Löfblom, J.; Orlova, A.; Deyev, S.; et al. Comparison of tumor-targeting properties of directly and indirectly radioiodinated designed ankyrin repeat protein (DARPin) G3 variants for molecular imaging of HER2. Int. J. Oncol. 2019, 4, 1209–1220. [Google Scholar] [CrossRef] [Green Version]
- Strand, J.; Nordeman, P.; Honarvar, H.; Altai, M.; Orlova, A.; Larhed, M.; Tolmachev, V. Site-specific radioiodination of HER2-targeting affibody molecules using 4-iodophenethylmaleimide decreases renal uptake of radioactivity. Chem. Open 2015, 4, 174–182. [Google Scholar] [CrossRef]
- Kramer-Marek, G.; Kiesewetter, D.O.; Martiniova, L.; Jagoda, E.; Lee, S.B.; Capala, J. [18F]FBEM-Z(HER2:342)-Affibody molecule-a new molecular tracer for in vivo monitoring of HER2 expression by positron emission tomography. Eur. J. Nucl. Med. Mol. Imaging 2008, 35, 1008–1018. [Google Scholar] [CrossRef] [Green Version]
- Chiotellis, A.; Sladojevich, F.; Mu, L.; Müller Herde, A.; Valverde, I.E.; Tolmachev, V.; Schibli, R.; Ametamey, S.M.; Mindt, T.L. Novel chemoselective (18)F-radiolabeling of thiol-containing biomolecules under mild aqueous conditions. Chem. Commun. (Camb.) 2016, 52, 6083–6086. [Google Scholar] [CrossRef]
- Rosik, D.; Thibblin, A.; Antoni, G.; Honarvar, H.; Strand, J.; Selvaraju, R.K.; Altai, M.; Orlova, A.; Eriksson Karlström, A.; Tolmachev, V. Incorporation of a triglutamyl spacer improves the biodistribution of synthetic affibody molecules radiofluorinated at the N-terminus via oxime formation with (18)F-4-fluorobenzaldehyde. Bioconjug. Chem. 2014, 25, 82–92. [Google Scholar] [CrossRef] [Green Version]
In Vitro Stability Test | [111In]In-(HE)3-ZHER3:08698-DOTAGA | [125I]I-PIB-(HE)3-ZHER3:08698-DOTAGA | |||
---|---|---|---|---|---|
5000× EDTA | PBS | 5000× KI | 30% EtOH | PBS | |
Protein-associated activity, % | 99 ± 0 | 99 ± 0 | 98 ± 0 | 99 ± 0 | 98 ± 0 |
Compound | KD1 (pM) |
---|---|
[125I]I-PIB-(HE)3-ZHER3:08698-DOTAGA | 98 ± 12 |
[111In]In-(HE)3-ZHER3:08698-DOTAGA | 19 ± 1 |
Organ | 4 h | 24 h | ||
---|---|---|---|---|
[125I]I-PIB | [111In]In | [125I]I-PIB | [111In]In | |
Blood | 0.37 ± 0.05 a,b | 0.06 ± 0.01 c | 0.05 ± 0.01 | 0.019 ± 0.002 |
Salivary glands | 0.18 ± 0.01 a,b | 1.1 ± 0.1 c | 0.02 ± 0.01 | 0.78 ± 0.07 |
Lung | 0.49 ± 0.06 a,b | 0.9 ± 0.2 c | 0.04 ± 0.01 | 0.31 ± 0.03 |
Liver | 0.32 ± 0.04 a,b | 3.3 ± 0.6 c | 0.05 ± 0.01 | 2.1 ± 0.4 |
Spleen | 0.12 ± 0.01 a,b | 0.5 ± 0.2 c | 0.027 ± 0.004 | 0.21 ± 0.02 |
Stomach | 0.22 ± 0.04 a,b | 1.3 ± 0.1 c | 0.02 ± 0.01 | 0.7 ± 0.1 |
Small intestine | 0.30 ± 0.07 a,b | 3.7 ± 0.8 c | 0.02 ± 0.02 | 1.6 ± 0.2 |
Kidney | 2.7 ± 0.7 a,b | 291 ± 39 c | 0.15 ± 0.02 | 211 ± 28 |
Tumor | 0.8 ± 0.1 a,b | 2.4 ± 0.1 c | 0.06 ± 0.04 | 1.7 ± 0.1 |
Muscle | 0.05 ± 0.02 a,b | 0.14 ± 0.02 c | 0.008 ± 0.002 | 0.07 ± 0.01 |
Bone | 0.4 ± 0.3 | 0.3 ± 0.1 c | 0.07 ± 0.02 | 0.10 ± 0.02 |
Organ | 4 h | 24 h | ||
---|---|---|---|---|
[125I]I-PIB | [111In]In | [125I]I-PIB | [111In]In | |
Blood | 2.0 ± 0.2 a,b | 43 ± 4 c | 1.6 ± 0.2 a | 88 ± 9 |
Salivary glands | 4.1 ± 0.4 a,b | 2.2 ± 0.1 | 3.3 ± 0.2 a | 2.1 ± 0.1 |
Lung | 1.5 ± 0.2 a | 2.6 ± 0.3 c | 1.7 ± 0.3 a | 5.4 ± 0.7 |
Liver | 2.4 ± 0.3 a,b | 0.7 ± 0.1 | 1.6 ± 0.2 a | 0.8 ± 0.1 |
Spleen | 7 ± 1 b | 5 ± 2 | 3.0 ± 0.6 a | 8 ± 1 |
Stomach | 3.5 ± 0.5 a | 1.9 ± 0.1 c | 5 ± 2 | 2.5 ± 0.2 |
Small intestine | 2.6 ± 0.5 a | 0.7 ± 0.1 c | 4 ± 2 a | 1.0 ± 0.1 |
Kidney | 0.3 ± 0.1 a,b | 0.008 ± 0.001 | 0.512 ± 0.002 a | 0.008 ± 0.001 |
Tumor | 15 ± 4 b | 18 ± 3 | 8 ± 3 a | 23 ± 4 |
Muscle | 3 ± 2 a | 11 ± 3 c | 1.1 ± 0.4 a | 18 ± 3 |
Bone | 2.0 ± 0.2 a,b | 43 ± 4 c | 1.6 ± 0.2 a | 88 ± 9 |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Rinne, S.S.; Xu, T.; Dahlsson Leitao, C.; Ståhl, S.; Löfblom, J.; Orlova, A.; Tolmachev, V.; Vorobyeva, A. Influence of Residualizing Properties of the Radiolabel on Radionuclide Molecular Imaging of HER3 Using Affibody Molecules. Int. J. Mol. Sci. 2020, 21, 1312. https://doi.org/10.3390/ijms21041312
Rinne SS, Xu T, Dahlsson Leitao C, Ståhl S, Löfblom J, Orlova A, Tolmachev V, Vorobyeva A. Influence of Residualizing Properties of the Radiolabel on Radionuclide Molecular Imaging of HER3 Using Affibody Molecules. International Journal of Molecular Sciences. 2020; 21(4):1312. https://doi.org/10.3390/ijms21041312
Chicago/Turabian StyleRinne, Sara S., Tianqi Xu, Charles Dahlsson Leitao, Stefan Ståhl, John Löfblom, Anna Orlova, Vladimir Tolmachev, and Anzhelika Vorobyeva. 2020. "Influence of Residualizing Properties of the Radiolabel on Radionuclide Molecular Imaging of HER3 Using Affibody Molecules" International Journal of Molecular Sciences 21, no. 4: 1312. https://doi.org/10.3390/ijms21041312