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Tolmachev, Vladimir
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Publications (10 of 266) Show all publications
Tolmachev, V., Yim, C.-B., Rajander, J., Perols, A., Karlstrom, A. E., Haaparanta-Solin, M., . . . Orlova, A. (2017). Comparative Evaluation of Anti-HER2 Affibody Molecules Labeled with Cu-64 Using NOTA and NODAGA. Contrast Media & Molecular Imaging, 1-12.
Open this publication in new window or tab >>Comparative Evaluation of Anti-HER2 Affibody Molecules Labeled with Cu-64 Using NOTA and NODAGA
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2017 (English)In: Contrast Media & Molecular Imaging, ISSN 1555-4309, E-ISSN 1555-4317, 1-12 p.Article in journal (Refereed) Published
Abstract [en]

Imaging using affi body molecules enables discrimination between breast cancer metastases with high and low expression of HER2, making appropriate therapy selection possible. This study aimed to evaluate if the longer half-life of Cu-64 (T-1/2 = 12.7h) would make Cu-64 a superior nuclide compared to Ga-68 for PET imaging of HER2 expression using affibody molecules. The synthetic ZHER2: S1 affibody molecule was conjugated with the chelators NOTA or NODAGA and labeled with Cu-64. The tumor-targeting properties of Cu-64-NOTA-ZHER2: S1 and Cu-64-NODAGA-ZHER2: S1 were evaluated and compared with the targeting properties of Ga-68-NODAGA-ZHER2: S1 in mice. Both 64 Cu-NOTA-ZHER2: S1 and Cu-64-NODAGA-ZHER2: S1 demonstrated specific targeting of HER2-expressing xenografts. At 2 h after injection of Cu-64-NOTA-ZHER2: S1, Cu-64-NODAGA-ZHER2: S1, and Ga-68-NODAGAZHER2: S1, tumor uptakes did not differ significantly. Renal uptake of Cu-64-labeled conjugateswas dramatically reduced at 6 and 24 h after injection. Notably, radioactivity uptake concomitantly increased in blood, lung, liver, spleen, and intestines, which resulted in decreased tumor-to-organ ratios compared to 2 h postinjection. Organ uptake was lower for Cu-64-NODAGA-ZHER2: S1. The most probable explanation for this biodistribution pattern was the release and redistribution of renal radiometabolites. In conclusion, monoamide derivatives of NOTA and NODAGA may be suboptimal chelators for radiocopper labeling of anti-HER2 affibody molecules and, possibly, other scaffold proteins with high renal uptake.

Place, publisher, year, edition, pages
WILEY-HINDAWI, 2017
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-322000 (URN)10.1155/2017/8565802 (DOI)000399198500001 ()
Funder
Swedish Cancer Society, CAN 2015/350 2014/474Swedish Research Council, 2015-02353 2013-5135 2015-02509
Available from: 2017-05-15 Created: 2017-05-15 Last updated: 2017-05-31Bibliographically approved
Honarvar, H., Müller, C., Cohrs, S., Haller, S., Westerlund, K., Karlström, A. E., . . . Tolmachev, V. (2017). Evaluation of the first (44)Sc-labeled Affibody molecule for imaging of HER2-expressing tumors. Nuclear Medicine and Biology, 45, 15-21.
Open this publication in new window or tab >>Evaluation of the first (44)Sc-labeled Affibody molecule for imaging of HER2-expressing tumors
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2017 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 45, 15-21 p.Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Affibody molecules are small (58 amino acids) high-affinity proteins based on a tri-helix non-immunoglobulin scaffold. A clinical study has demonstrated that PET imaging using Affibody molecules labeled with (68)Ga (T½=68min) can visualize metastases of breast cancer expressing human epidermal growth factor receptor type 2 (HER2) and provide discrimination between tumors with high and low expression level. This may help to identify breast cancer patients benefiting from HER2-targeting therapies. The best discrimination was at 4h post injection. Due to longer half-life, a positron-emitting radionuclide (44)Sc (T½=4.04h) might be a preferable label for Affibody molecules for imaging at several hours after injection.

METHODS: A synthetic second-generation anti-HER2 Affibody molecule ZHER2:2891 was labeled with (44)Sc via a DOTA-chelator conjugated to the N-terminal amino group. Binding specificity, affinity and cellular processing (44)Sc-DOTA-ZHER2:2891 and (68)Ga-DOTA-ZHER2:2891 were compared in vitro using HER2-expressing cells. Biodistribution and imaging properties of (44)Sc-DOTA-ZHER2:2891 and (68)Ga-DOTA-ZHER2:2891 were evaluated in Balb/c nude mice bearing HER2-expression xenografts.

RESULTS: The labeling yield of 98±2% and specific activity of 7.8GBq/μmol were obtained. The conjugate demonstrated specific binding to HER2-expressing SKOV3.ip cells in vitro and to SKOV3.ip xenografts in nude mice. The distribution of radioactivity at 3h post injection was similar for (44)Sc-DOTA-ZHER2:2891 and (68)Ga-DOTA-ZHER2:2891, but the blood clearance of the (44)Sc-labeled variant was slower and the tumor-to-blood ratio was reduced (15±2 for (44)Sc-DOTA-ZHER2:2891 vs 46±9 for (68)Ga-DOTA-ZHER2:2891). At 6h after injection of (44)Sc-DOTA-ZHER2:2891 the tumor uptake was 8±2% IA/g and the tumor-to-blood ratio was 51±8. Imaging using small-animal PET/CT demonstrated that (44)Sc-DOTA-ZHER2:2891 provides specific and high-contrast imaging of HER2-expressing xenografts.

CONCLUSION: The (44)Sc- DOTA-ZHER2:2891 Affibody molecule is a promising probe for imaging of HER2-expression in malignant tumors.

Keyword
Affibody molecule, Sc-44, DOTA, Z(HER2-2891), HER2, PET imaging
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-312076 (URN)10.1016/j.nucmedbio.2016.10.004 (DOI)000392366900003 ()27837664 (PubMedID)
Funder
Swedish Cancer Society, 2015/350 CAN2015/890Swedish Research Council, 2013-5135 2015-02353
Available from: 2017-01-04 Created: 2017-01-04 Last updated: 2017-11-29Bibliographically approved
Mitran, B., Thisgaard, H., Rosenström, U., Dam, J. H., Larhed, M., Tolmachev, V. & Orlova, A. (2017). High Contrast PET Imaging of GRPR Expression in Prostate Cancer Using Cobalt-Labeled Bombesin Antagonist RM26. Contrast Media & Molecular Imaging, Article ID UNSP 6873684.
Open this publication in new window or tab >>High Contrast PET Imaging of GRPR Expression in Prostate Cancer Using Cobalt-Labeled Bombesin Antagonist RM26
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2017 (English)In: Contrast Media & Molecular Imaging, ISSN 1555-4309, E-ISSN 1555-4317, UNSP 6873684Article in journal (Refereed) Published
Abstract [en]

High gastrin releasing peptide receptor (GRPR) expression is associated with numerous cancers including prostate and breast cancer. The aim of the current study was to develop a Co-55-labeled PET agent based on GRPR antagonist RM26 for visualization of GRPR-expressing tumors. Labeling with Co-57 and Co-55, stability, binding specificity, and in vitro and in vivo characteristics of Co-57-NOTA-PEG(2)-RM26 were studied. NOTA-PEG(2)-RM26 was successfully radiolabeled with Co-57 and Co-55 with high yields and demonstrated high stability. The radiopeptide showed retained binding specificity to GRPR in vitro and in vivo. Co-57-NOTA-PEG(2)-RM26 biodistribution in mice was characterized by rapid clearance of radioactivity from blood and normal non-GRPR-expressing organs and low hepatic uptake. The clearance was predominantly renal with a low degree of radioactivity reabsorption. Tumor-to-blood ratios were approximately 200 (3 h pi) and 1000 (24 h pi). The favorable biodistribution of cobalt-labeled NOTA-PEG(2)-RM26 translated into high contrast preclinical PET/CT (using Co-55) and SPECT/CT (using Co-57) images of PC-3 xenografts. The initial biological results suggest that Co-55-NOTA-PEG(2)-RM26 is a promising tracer for PET visualization of GRPR-expressing tumors.

Keyword
Positron-Emission-Tomography, Receptor-Positive Tumors, In-Vivo Evaluation, Radiolabeled Peptides, Analog; Agonists, Visualization, Proteins, Affinity, Therapy.
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-334114 (URN)10.1155/2017/6873684 (DOI)000408099300001 ()
Funder
Swedish Cancer Society, CAN2014/474; CAN2015/350Swedish Research Council, 2015-02509; 2015-02353Knut and Alice Wallenberg FoundationScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2017-11-24 Created: 2017-11-24 Last updated: 2017-11-24Bibliographically approved
Bass, T. Z., Rosestedt, M., Mitran, B., Frejd, F. Y., Löfblom, J., Tolmachev, V., . . . Orlova, A. (2017). In vivo evaluation of a novel format of a bivalent HER3-targeting and albumin- binding therapeutic affibody construct. Scientific Reports, 7, Article ID 43118.
Open this publication in new window or tab >>In vivo evaluation of a novel format of a bivalent HER3-targeting and albumin- binding therapeutic affibody construct
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 43118Article in journal (Refereed) Published
Abstract [en]

Overexpression of human epidermal growth factor receptor 3 (HER3) is involved in resistance to several therapies for malignant tumours. Currently, several anti-HER3 monoclonal antibodies are under clinical development. We introduce an alternative approach to HER3-targeted therapy based on engineered scaffold proteins, i.e. affibody molecules. We designed a small construct (22.5 kDa, denoted 3A3), consisting of two high-affinity anti-HER3 affibody molecules flanking an albumin-binding domain ABD, which was introduced for prolonged residence in circulation. In vitro, 3A3 efficiently inhibited growth of HER3-expressing BxPC-3 cells. Biodistribution in mice was measured using 3A3 that was site-specifically labelled with In-111 via a DOTA chelator. The residence time of In-111-DOTA-3A3 in blood was extended when compared with the monomeric affibody molecule. In-111-DOTA-3A3 accumulated specifically in HER3-expressing BxPC-3 xenografts in mice. However, In-111-DOTA-3A3 cleared more rapidly from blood than a size-matched control construct In-111-DOTA-TAT, most likely due to sequestering of 3A3 by mErbB3, the murine counterpart of HER3. Repeated dosing and increase of injected protein dose decreased uptake of In-111-DOTA-3A3 in mErbB3-expressing tissues. Encouragingly, growth of BxPC-3 xenografts in mice was delayed in an experimental (pilot-scale) therapy study using 3A3. We conclude that the 3A3 affibody format seems promising for treatment of HER3-overexpressing tumours.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-318958 (URN)10.1038/srep43118 (DOI)000394748000001 ()28230065 (PubMedID)
Funder
Swedish Cancer Society, CAN2013-586, CAN 2016/463, CAN2014-474, CAN2015/350Swedish Research Council, Swedish Research Council 621-2012-5236, 2015-02509, 2015-02353VINNOVA, 2016-04060
Available from: 2017-03-30 Created: 2017-03-30 Last updated: 2017-11-29Bibliographically approved
Sandberg, D. T., Tolmachev, V., Velikyan, I., Olofsson, H., Wennborg, A., Feldwisch, J., . . . Sörensen, J. (2017). Intra-image referencing for simplified assessment of HER2-expression in breast cancer metastases using the Affibody molecule ABY-025 with PET and SPECT.. European Journal of Nuclear Medicine and Molecular Imaging, 44(8), 1337-1346.
Open this publication in new window or tab >>Intra-image referencing for simplified assessment of HER2-expression in breast cancer metastases using the Affibody molecule ABY-025 with PET and SPECT.
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2017 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 44, no 8, 1337-1346 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: In phase I/II-studies radiolabelled ABY-025 Affibody molecules identified human epidermal growth factor receptor 2 (HER2) expression in breast cancer metastases using PET and SPECT imaging. Here, we wanted to investigate the utility of a simple intra-image normalization using tumour-to-reference tissue-ratio (T/R) as a HER2 status discrimination strategy to overcome potential issues related to cross-calibration of scanning devices.

METHODS: Twenty-three women with pre-diagnosed HER2-positive/negative metastasized breast cancer were scanned with [(111)In]-ABY-025 SPECT/CT (n = 7) or [(68)Ga]-ABY-025 PET/CT (n = 16). Uptake was measured in all metastases and in normal spleen, lung, liver, muscle, and blood pool. Normal tissue uptake variation and T/R-ratios were established for various time points and for two different doses of injected peptide from a total of 94 whole-body image acquisitions. Immunohistochemistry (IHC) was used to verify HER2 expression in 28 biopsied metastases. T/R-ratios were compared to IHC findings to establish the best reference tissue for each modality and each imaging time-point. The impact of shed HER2 in serum was investigated.

RESULTS: Spleen was the best reference tissue across modalities, followed by blood pool and lung. Spleen-T/R was highly correlated to PET SUV in metastases after 2 h (r = 0.96, P < 0.001) and reached an accuracy of 100% for discriminating IHC HER2-positive and negative metastases at 4 h (PET) and 24 h (SPECT) after injection. In a single case, shed HER2 resulted in intense tracer retention in blood. In the remaining patients shed HER2 was elevated, but without significant impact on ABY-025 biodistribution.

CONCLUSION: T/R-ratios using spleen as reference tissue accurately quantify HER2 expression with radiolabelled ABY-025 imaging in breast cancer metastases with SPECT and PET. Tracer binding to shed HER2 in serum might affect quantification in the extreme case.

Keyword
Affibody, HER2-receptor, PET, SPECT, Shedding, T/R
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-317746 (URN)10.1007/s00259-017-3650-3 (DOI)000403468900012 ()28261749 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2017-03-17 Created: 2017-03-17 Last updated: 2017-09-14Bibliographically approved
Garousi, J., Andersson, K. G., Dam, J. H., Olsen, B. B., Mitran, B., Orlova, A., . . . Tolmachev, V. (2017). The use of radiocobalt as a label improves imaging of EGFR using DOTA-conjugated Affibody molecule. Scientific Reports, 7, Article ID 5961.
Open this publication in new window or tab >>The use of radiocobalt as a label improves imaging of EGFR using DOTA-conjugated Affibody molecule
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 5961Article in journal (Refereed) Published
Abstract [en]

Several anti-cancer therapies target the epidermal growth factor receptor (EGFR). Radionuclide imaging of EGFR expression in tumours may aid in selection of optimal cancer therapy. The In-111-labelled DOTA-conjugated Z(EGFR:2377) Affibody molecule was successfully used for imaging of EGFR-expressing xenografts in mice. An optimal combination of radionuclide, chelator and targeting protein may further improve the contrast of radionuclide imaging. The aim of this study was to evaluate the targeting properties of radiocobalt-labelled DOTA-Z(EGFR:2377). DOTA-Z(EGFR:2377) was labelled with Co-57 (T-1/2 = 271.8 d), Co-55 (T-1/2 = 17.5 h), and, for comparison, with the positron-emitting radionuclide Ga-68 (T-1/2 = 67.6 min) with preserved specificity of binding to EGFR-expressing A431 cells. The long-lived cobalt radioisotope Co-57 was used in animal studies. Both Co-57-DOTA-Z(EGFR:2377) and Ga-68-DOTA-Z(EGFR:2377) demonstrated EGFR-specific accumulation in A431 xenografts and EGFR-expressing tissues in mice. Tumour-to-organ ratios for the radiocobalt-labelled DOTA-Z(EGFR:2377) were significantly higher than for the gallium-labelled counterpart already at 3 h after injection. Importantly, Co-57-DOTA-Z(EGFR:2377) demonstrated a tumour-to-liver ratio of 3, which is 7-fold higher than the tumour-to-liver ratio for (68)GaDOTA-Z(EGFR:2377). The results of this study suggest that the positron-emitting cobalt isotope 55Co would be an optimal label for DOTA-Z(EGFR:2377) and further development should concentrate on this radionuclide as a label.

Keyword
Epidermal-Growth-Factor; Factor Receptor Expression; Cell Lung-Cancer; Monoclonal-Antibody; Integrin Expression; Somatostatin Analog; Quantitative Pet; Positive Tumors; Carcinoma; Head
National Category
Cancer and Oncology Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-334098 (URN)10.1038/s41598-017-05700-7 (DOI)000405907800015 ()28729680 (PubMedID)
Available from: 2017-11-21 Created: 2017-11-21 Last updated: 2018-01-13Bibliographically approved
Sandström, M., Lindskog, K., Velikyan, I., Wennborg, A., Feldwisch, J., Sandberg, D., . . . Lubberink, M. (2016). Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule Ga-68-ABY-025 in Breast Cancer Patients. Journal of Nuclear Medicine, 57(6), 867-871.
Open this publication in new window or tab >>Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule Ga-68-ABY-025 in Breast Cancer Patients
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2016 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 57, no 6, 867-871 p.Article in journal (Refereed) Published
Abstract [en]

Ga-68-ABY-025 is a radiolabeled Affibody molecule for in vivo diagnosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer tumors with PET. The aim of the present work was to measure the biodistribution and estimate the radiation dosimetry of Ga-68-ABY-025 for 2 different peptide mass doses in a single group of patients using dynamic and serial whole-body PET/CT. Methods: Eight patients with metastatic breast cancer were included. Each patient underwent an abdominal 45-min dynamic and 3 whole-body PET/CT scans at 1, 2, and 4 h after injection of a low peptide dose (LD) and a high peptide dose (HD), with approximately the same amount of radioactivity, in separate investigations 1 wk apart. As input to the absorbed dose calculations, volumes of interest were drawn on all clearly identifiable source organs: liver, kidneys, spleen, descending aorta, and upper large intestine. Absorbed doses were calculated using OLINDA/EXM, version 1.1. Results: Of the major organs, the highest radionuclide uptake at 1, 2, and 4 h after injection was observed in the kidneys and liver. The highest absorbed organ doses were seen in the kidneys, followed by the liver for both LD and HD Ga-68-ABY-025. Absorbed doses to liver and kidneys were slightly but significantly higher for LD. Total effective dose was 0.030 +/- 0.003 mSv/MBq for LD and 0.028 +/- 0.002 mSv/MBq for HD. Conclusion: The effective dose for a typical 200-MBq administration of Ga-68-ABY-025 is 6.0 mSv for LD and 5.6 mSv for HD. Therefore, from a radiation dosimetry point of view, HD is preferred for PET/CT evaluation of HER2-expressing breast cancer tumors. These effective doses are somewhat higher than earlier published values for other Ga-68-labeled tracers, such as 0.021 +/- 0.003 mSv/MBq for Ga-68-DOTATATE and Ga-68-DOTATOC, mainly because of higher uptake in liver and kidney.

Keyword
Affibody, breast cancer metastases, dosimetry, HER2-receptor, Ga-68-gallium
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-298861 (URN)10.2967/jnumed.115.169342 (DOI)000377052400035 ()26912439 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2016-07-11 Created: 2016-07-11 Last updated: 2017-11-28Bibliographically approved
Garousi, J., Honarvar, H., Andersson, K. G., Mitran, B., Orlova, A., Buijs, J., . . . Tolmachev, V. (2016). Comparative evaluation of Affibody molecules for radionuclide imaging of in vivo expression of carbonic anhydrase IX. Molecular Pharmaceutics, 13(11), 3676-3687.
Open this publication in new window or tab >>Comparative evaluation of Affibody molecules for radionuclide imaging of in vivo expression of carbonic anhydrase IX
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2016 (English)In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 13, no 11, 3676-3687 p.Article in journal (Refereed) Published
Abstract [en]

Overexpression of the enzyme carbonic anhydrase IX (CAIX) is documented for chronically hypoxic malignant tumors as well as for normoxic renal cell carcinoma. Radionuclide molecular imaging of CAIX would be useful for detection of hypoxic areas in malignant tumors, for patients' stratification of CAIX-targeted therapies and for discrimination of primary malignant and benign renal tumors. Earlier, we have reported feasibility of in vivo radionuclide based imaging of CAIX expressing tumors using Affibody molecules, small affinity proteins based on a non-immunoglobulin scaffold. In this study, we compared imaging properties of several anti-CAIX Affibody molecules having identical scaffold parts and competing for the same epitope on CAIX, but having different binding paratopes. Four variants were labeled using residualizing 99mTc and non-residualizing 125I labels. All radiolabeled variants demonstrated high-affinity detection of CAIX-expressing cell line SK-RC-52 in vitro and specific accumulation in SK-RC-52 xenografts in vivo. 125I-labeled conjugates demonstrated much lower radioactivity uptake in kidneys but higher radioactivity concentration in blood compared with 99mTc-labed counterparts. Although all variants cleared rapidly from blood and non-specific compartments, there was noticeably difference in their biodistribution. The best variant for imaging of expression of CAIX- in disseminated cancer was 99mTc-(HE)3-ZCAIX:2 providing tumor uptake of 16.3±0.9 %ID/g and tumor-to-blood ratio of 44±7 at 4 h after injection. For primary renal cell carcinoma, the most promising imaging candidate was 125I-ZCAIX:4 providing tumor-kidney ratio of 2.1±0.5. In conclusion, several clones of scaffold proteins should be evaluated to select the best variant for development of an imaging probe with optimal sensitivity for the intended application.

Keyword
CAIX, affibody molecule, imaging, radionuclide
National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-302639 (URN)10.1021/acs.molpharmaceut.6b00502 (DOI)000387428300008 ()27529191 (PubMedID)
Funder
Swedish Cancer Society, 2014/474 2015/350Swedish Research Council, 2015-02353 2015-02509
Available from: 2016-09-07 Created: 2016-09-07 Last updated: 2017-11-21Bibliographically approved
Altai, M., Westerlund, K., Velletta, J., Honarvar, H., Orlova, A., Eriksson-Karlström, A. & Tolmachev, V. (2016). Comparative evaluation of Lu-177-HP2 and In-111-HP2, secondary agents for affibody-based PNA-mediated radionuclide pretargeting. Paper presented at Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 15-19, 2016, Barcelona, SPAIN. European Journal of Nuclear Medicine and Molecular Imaging, 43, S237-S237.
Open this publication in new window or tab >>Comparative evaluation of Lu-177-HP2 and In-111-HP2, secondary agents for affibody-based PNA-mediated radionuclide pretargeting
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2016 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, S237-S237 p.Article in journal, Meeting abstract (Refereed) Published
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-316213 (URN)000391801600594 ()
Conference
Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 15-19, 2016, Barcelona, SPAIN
Available from: 2017-02-27 Created: 2017-02-27 Last updated: 2017-11-29Bibliographically approved
Kootala, S., Zhang, Y., Ghalib, S., Tolmachev, V., Hilborn, J. & Ossipov, D. (2016). Control of growth factor binding and release in bisphosphonate functionalized hydrogels guides rapid diff erentiation of precursor cells in vitro. Biomaterials Science, 4(2), 250-254.
Open this publication in new window or tab >>Control of growth factor binding and release in bisphosphonate functionalized hydrogels guides rapid diff erentiation of precursor cells in vitro
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2016 (English)In: Biomaterials Science, ISSN 2047-4830, E-ISSN 2047-4849, Vol. 4, no 2, 250-254 p.Article in journal (Refereed) Published
Abstract [en]

An in situ cross-linkable hyaluronan hydrogel functionalized with bisphosphonate (BP) groups allows tunable release of bone morphogenetic protein-2 (BMP-2) determined by the amount of BP groups. The high affinity of matrix-anchored BP groups towards BMP-2 permits guided differentiation of entrapped progenitor cells in 3-D cultures.

Place, publisher, year, edition, pages
UK: Royal Society of Chemistry, 2016
Keyword
bone, hyaluronic acid, bisphosphonates, growth factor, delivery, stem cells
National Category
Polymer Chemistry
Research subject
Chemistry with specialization in Materials Chemistry; Chemistry with specialization in Polymer Chemistry; Biology with specialization in Molecular Biology
Identifiers
urn:nbn:se:uu:diva-267600 (URN)10.1039/c5bm00355e (DOI)000368945400005 ()26610690 (PubMedID)
External cooperation:
Funder
EU, European Research Council, 262948-2EU, FP7, Seventh Framework Programme, 238551
Available from: 2015-11-25 Created: 2015-11-25 Last updated: 2017-12-01Bibliographically approved
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