Change search
ReferencesLink to record
Permanent link

Direct link
Feasibility of Affibody-Based Bioorthogonal Chemistry Mediated Radionuclide Pretargeting
KTH, School of Biotechnology (BIO), Protein Technology.
Show others and affiliations
2016 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 57, no 3, 431-436 p.Article in journal (Refereed) PublishedText
Abstract [en]

Affibody molecules constitute a new class of probes for radionuclide tumor targeting. The small size of Affibody molecules is favorable for rapid localization in tumors and clearance from circulation. However, high renal reabsorption of Affibody molecules prevents the use of residualizing radiometals, including several promising low-energy (beta- and alpha-emitters, for radionuclide therapy. We tested a hypothesis that Affibody-based pretargeting mediated by a bioorthogonal interaction between trans-cyclooctene (TCO) and tetrazine would provide higher accumulation of radiometals in tumor xenografts than in the kidneys. Methods: TCO was conjugated to the anti-human epidermal growth factor receptor 2 (HER2) Affibody molecule Z(2395). DOTA-tetrazine was labeled with In-111 and Lu-177. In vitro pretargeting was studied in HER2-expressing SKOV-3 and BT474 cell lines. In vivo studies were performed on BALB/C nu/nu mice bearing SKOV-3 xenografts. Results: I-125-Z(2395)-TCO bound specifically to HER2-expressing cells in vitro with an affinity of 45 +/- 16 pM. In-111-tetrazine bound specifically and selectively to Z(2325)-TCO pretreated cells. In vivo studies demonstrated HER2-specific I-125-Z(2395)-TCO accumulation in xenografts. TCO-mediated In-111-tetrazine localization was shown in tumors, when the radiolabeled tracer was injected 4 h after an injection of Z(2395)-TCO. At 1 h after injection, the tumor uptake of In-111-tetrazine and Lu-177-tetrazine was approximately 2-fold higher than the renal uptake. Pretargeting provided more than a 56-fold reduction of renal uptake of In-111 in comparison with direct targeting. Conclusion: The feasibility of Affibody-based bioorthogonal chemistry-mediated pretargeting was demonstrated. The use of pre-targeting provides a substantial reduction of radiometal accumulation in kidneys, creating preconditions for palliative radionuclide therapy.

Place, publisher, year, edition, pages
SOC NUCLEAR MEDICINE , 2016. Vol. 57, no 3, 431-436 p.
Keyword [en]
affibody, tetrazine, trans-cyclooctene, radionuclide pretargeting, engineered scaffold protein, radionuclide therapy
National Category
Radiology, Nuclear Medicine and Medical Imaging
URN: urn:nbn:se:kth:diva-184961DOI: 10.2967/jnumed.115.162248ISI: 000371371800037PubMedID: 26659353ScopusID: 2-s2.0-84960118391OAI: diva2:917811
Swedish Research Council, 521-2012-2228; 621-2013-5135

QC 20160407

Available from: 2016-04-07 Created: 2016-04-07 Last updated: 2016-04-07Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Perols, AnnaKarlström, Amelie Eriksson
By organisation
Protein Technology
In the same journal
Journal of Nuclear Medicine
Radiology, Nuclear Medicine and Medical Imaging

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 46 hits
ReferencesLink to record
Permanent link

Direct link