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Spiegelberg, Diana
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Publications (10 of 36) Show all publications
Spiegelberg, D., Mortensen, A. C., Lundsten, S., Brown, C. J., Lane, D. P. & Nestor, M. (2018). First in vivo study of the MDM2/MDMX-p53 antagonist PM2 as potentiator of external radiotherapy in wt p53 cancer. Paper presented at 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY. European Journal of Nuclear Medicine and Molecular Imaging, 45(Supplement: 1), S30-S30
Open this publication in new window or tab >>First in vivo study of the MDM2/MDMX-p53 antagonist PM2 as potentiator of external radiotherapy in wt p53 cancer
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2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, no Supplement: 1, p. S30-S30Article in journal, Meeting abstract (Other academic) Published
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-373337 (URN)10.1007/s00259-018-4148-3 (DOI)000449266200037 ()
Conference
31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY
Note

Meeting Abstract OP-074

Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2019-01-14Bibliographically approved
Lundsten, S., Spiegelberg, D., Raval, N., Stenerlöw, B. & Nestor, M. (2018). Potentiating Lu-177-DOTATATE Therapy By HSP90 Inhibition - First In Vivo Study. Paper presented at 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY. European Journal of Nuclear Medicine and Molecular Imaging, 45, S12-S13
Open this publication in new window or tab >>Potentiating Lu-177-DOTATATE Therapy By HSP90 Inhibition - First In Vivo Study
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2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S12-S13Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-372968 (URN)000449266200003 ()
Conference
31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY
Available from: 2019-01-11 Created: 2019-01-11 Last updated: 2019-01-11Bibliographically approved
Mortensen, A., Spiegelberg, D., Haylock, A.-K., Lundqvist, H. & Nestor, M. (2018). Preclinical evaluation of a novel engineered recombinant human anti-CD44v6 antibody for potential use in radio-immunotherapy. International Journal of Oncology, 52(6), 1875-1885
Open this publication in new window or tab >>Preclinical evaluation of a novel engineered recombinant human anti-CD44v6 antibody for potential use in radio-immunotherapy
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2018 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 52, no 6, p. 1875-1885Article in journal (Refereed) Published
Abstract [en]

CD44v6 is overexpressed in a variety of cancers, rendering it a promising target for radio-immunotherapy (RIT). In this study, we have characterized a novel engineered recombinant monoclonal anti-CD44v6 antibody, AbN44v6, and assessed its potential for use in RIT using either Lu-177 or I-131 as therapeutic radionuclides. In vitro affinity and specificity assays characterized the binding of the antibody labeled with Lu-177, I-125 or I-131. The therapeutic effects of Lu-177-AbN44v6 and I-131-AbN44v6 were investigated using two in vitro 3D tumor models with different CD44v6 expression. Finally, the normal tissue biodistribution and dosimetry for Lu-177-AbN44v6 and I-125-AbN44v6/I-131-AbN44v6 were assessed in vivo using a mouse model. All AbN44v6 radioconjugates demonstrated CD44v6-specific binding in vitro. In the in vitro 3D tumor models, dose-dependent therapeutic effects were observed with both Lu-177-AbN44v6 and I-131-AbN44v6, with a greater significant therapeutic effect observed on the cells with a higher CD44v6 expression. Biodistribution experiments demonstrated a greater uptake of Lu-177-AbN44v6 in the liver, spleen and bone, compared to I-125-AbN44v6, whereas I-125-AbN44v6 demonstrated a longer circulation time. In dosimetric calculations, the critical organs for Lu-177-AbN44v6 were the liver and spleen, whereas the kidneys and red marrow were considered the critical organs for I-131-AbN44v6. The effective dose was in the order of 0.1 mSv/MBq for both labels. In conclusion, AbN44v6 bound specifically and with high affinity to CD44v6. Furthermore, in vitro RIT demonstrated growth inhibition in a CD44v6-specific activity-dependent manner for both radioconjugates, demonstrating that both Lu-177-AbN44v6 and I-131-AbN44v6 may be promising RIT candidates. Furthermore, biodistribution and dosimetric analysis supported the applicability of both conjugates for RIT. The CD44v6-specific therapeutic effects observed with radiolabeled AbN44v6 in the 3D tumor models in vitro, combined with the beneficial dosimetry in vivo, render AbN44v6 a potential candidate for RIT.

Place, publisher, year, edition, pages
SPANDIDOS PUBL LTD, 2018
Keywords
radio-immunotherapy, 3D tumor models, dosimetry, biodistribution, Lu-177, I-131
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-356443 (URN)10.3892/ijo.2018.4364 (DOI)000432241200010 ()29658563 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer Society
Available from: 2018-07-31 Created: 2018-07-31 Last updated: 2018-07-31Bibliographically approved
Abramenkovs, A., Spiegelberg, D. & Stenerlöw, B. (2018). Ra223 induced clustered DNA damage reduces cell survival independently of androgen receptor variant 7 expression. Paper presented at 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY. European Journal of Nuclear Medicine and Molecular Imaging, 45, S634-S635
Open this publication in new window or tab >>Ra223 induced clustered DNA damage reduces cell survival independently of androgen receptor variant 7 expression
2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S634-S635Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-372955 (URN)000449266206036 ()
Conference
31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY
Available from: 2019-01-24 Created: 2019-01-24 Last updated: 2019-01-24Bibliographically approved
Spiegelberg, D., Mortensen, A., Lundsten, S., Brown, C. J., Lane, D. P. & Nestor, M. (2018). The MDM2/MDMX-p53 Antagonist PM2 Radiosensitizes Wild-Type p53 Tumors. Cancer Research, 78(17), 5084-5093
Open this publication in new window or tab >>The MDM2/MDMX-p53 Antagonist PM2 Radiosensitizes Wild-Type p53 Tumors
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2018 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 78, no 17, p. 5084-5093Article in journal (Refereed) Published
Abstract [en]

Radiotherapy amplifies p53 expression in cancer cells with wild-type (wt) p53. Blocking the negative regulators MDM2 and MDMX stabilizes p53 and may therefore potentiate radiotherapy outcomes. In this study, we investigate the efficacy of the novel anti-MDM2/X stapled peptide PM2 alone and in combination with externalgamma radiation in vitro and in vivo. PM2 therapy combined with radiotherapy elicited synergistic therapeutic effects compared with monotherapy in cells with wt p53 in both in vitro and in vivo assays, whereas these effects did not manifest in p53(-/-) cells. Biodistribution and autoradiography of 125I-PM2 revealed high and retained uptake homogenously distributed throughout the tumor. In mice carrying wt p53 tumors, PM2 combined with radiother-apy significantly prolonged the median survival by 50%, whereas effects of PM2 therapy on mutant and p53(-/-) tumors were negligible. PM2-dependent stabilization of p53 was confirmed with ex vivo immunohistochemistry. These data demonstrate the potential of the stapled peptide PM2 as a radiotherapy potentiator in vivo and suggest that clinical application of PM2 with radiotherapy in wt p53 cancers might improve tumor control.

Significance: These findings contribute advances to cancer radiotherapy by using novel p53-reactivating stapled peptides as radiosensitizers in wild-type p53 cancers.

Place, publisher, year, edition, pages
AMER ASSOC CANCER RESEARCH, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-365821 (URN)10.1158/0008-5472.CAN-18-0440 (DOI)000443753700024 ()30026328 (PubMedID)
Funder
Swedish Research Council, 2013-30876-104113-30Swedish Research Council, 2013-8807Swedish Cancer Society, CAN 2015/1080Swedish Cancer Society, CAN 2015/385
Available from: 2018-11-26 Created: 2018-11-26 Last updated: 2018-11-26Bibliographically approved
Spiegelberg, D. & Nilvebrant, J. (2017). CD44v6-Targeted Imaging of Head and Neck Squamous Cell Carcinoma: Antibody-Based Approaches. Contrast Media & Molecular Imaging, 2017, Article ID 2709547.
Open this publication in new window or tab >>CD44v6-Targeted Imaging of Head and Neck Squamous Cell Carcinoma: Antibody-Based Approaches
2017 (English)In: Contrast Media & Molecular Imaging, ISSN 1555-4309, E-ISSN 1555-4317, Vol. 2017, article id 2709547Article, review/survey (Refereed) Published
Abstract [en]

Head and neck squamous cell carcinoma (HNSCC) is a common and severe cancer with low survival rate in advanced stages. Noninvasive imaging of prognostic and therapeutic biomarkers could provide valuable information for planning and monitoring of the different therapy options. Thus, there is amajor interest in development of new tracers towards cancer-specific molecular targets to improve diagnostic imaging and treatment. CD44v6, an oncogenic variant of the cell surface molecule CD44, is a promising molecular target since it exhibits a unique expression pattern in HNSCC and is associated with drug-and radio-resistance.

In this review we summarize results from preclinical and clinical investigations of radiolabeled anti-CD44v6 antibody-based tracers: full-length antibodies, Fab, F(ab')(2) fragments, and scFvs with particular focus on the engineering of various antibody formats and choice of radiolabel for the use as molecular imaging agents in HNSCC. We conclude that the current evidence points to CD44v6 imaging being a promising approach for providing more specific and sensitive diagnostic tools, leading to customized treatment decisions and functional diagnosis. Improved imaging tools hold promise to enable more effective treatment for head and neck cancer patients.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-335835 (URN)10.1155/2017/2709547 (DOI)000404941200001 ()29097914 (PubMedID)
Available from: 2017-12-15 Created: 2017-12-15 Last updated: 2017-12-15Bibliographically approved
Spiegelberg, D. (2017). HSP90 inhibition in angiosarcoma. British Journal of Dermatology, 177(2), 343-344
Open this publication in new window or tab >>HSP90 inhibition in angiosarcoma
2017 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 177, no 2, p. 343-344Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
WILEY, 2017
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:uu:diva-345889 (URN)10.1111/bjd.15609 (DOI)000407994100015 ()28833016 (PubMedID)
Available from: 2018-03-13 Created: 2018-03-13 Last updated: 2018-03-13Bibliographically approved
Spiegelberg, D., Lundsten, S., Mortensen, A. C., Abramenkovs, A., Stenerlöw, B. & Nestor, M. (2017). In Vitro and In Vivo Growth Inhibitory and Radiosensitizing Effects of the Anti-HSP90 agent Onalespib. European Journal of Nuclear Medicine and Molecular Imaging, 44, S182-S182
Open this publication in new window or tab >>In Vitro and In Vivo Growth Inhibitory and Radiosensitizing Effects of the Anti-HSP90 agent Onalespib
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2017 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 44, p. S182-S182Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2017
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-377089 (URN)000455019400106 ()
Available from: 2019-02-19 Created: 2019-02-19 Last updated: 2019-02-19Bibliographically approved
Mortensen, A. C., Spiegelberg, D., Lundsten, S., Brown, C., Lane, D. P. & Nestor, M. (2017). In Vivo Assessment of p53 Therapy as a Way of Enhancing Therapeutic Effects of Radiation. European Journal of Nuclear Medicine and Molecular Imaging, 44, S181-S181
Open this publication in new window or tab >>In Vivo Assessment of p53 Therapy as a Way of Enhancing Therapeutic Effects of Radiation
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2017 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 44, p. S181-S181Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2017
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-377082 (URN)000455019400104 ()
Available from: 2019-02-20 Created: 2019-02-20 Last updated: 2019-02-20Bibliographically approved
Lundsten, S., Spiegelberg, D., Agmo Hernández, V., Brown, C., Edwards, K., Lane, D. & Nestor, M. (2017). Radioiodination Of Small Stapled Peptides For p53 Therapy. European Journal of Nuclear Medicine and Molecular Imaging, 44, S769-S769
Open this publication in new window or tab >>Radioiodination Of Small Stapled Peptides For p53 Therapy
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2017 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 44, p. S769-S769Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2017
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-377079 (URN)000455019402544 ()
Available from: 2019-02-21 Created: 2019-02-21 Last updated: 2019-02-21Bibliographically approved
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