Change search
ReferencesLink to record
Permanent link

Direct link
Feasibility of Affibody Molecule-Based PNA-Mediated Radionuclide Pretargeting of Malignant Tumors
KTH, School of Biotechnology (BIO), Protein Technology.ORCID iD: 0000-0003-4334-9360
Show others and affiliations
2016 (English)In: Theranostics, ISSN 1838-7640, E-ISSN 1838-7640, Vol. 6, no 1, 93-103 p.Article in journal (Refereed) PublishedText
Abstract [en]

Affibody molecules are small (7 kDa), non-immunoglobulin scaffold proteins with a potential as targeting agents for radionuclide imaging of cancer. However, high renal re-absorption of Affibody molecules prevents their use for radionuclide therapy with residualizing radiometals. We hypothesized that the use of Affibody-based peptide nucleic acid (PNA)-mediated pretargeting would enable higher accumulation of radiometals in tumors than in kidneys. To test this hypothesis, we designed an Affibody-PNA chimera Z(HER2:342)-SR-HP1 containing a 15-mer HP1 PNA recognition tag and a complementary HP2 hybridization probe permitting labeling with both I-125 and In-111. In-111-Z(HER2:342)-SR-HP1 bound specifically to HER2-expressing BT474 and SKOV-3 cancer cells in vitro, with a K-D of 6+/-2 pM for binding to SKOV-3 cells. Specific high affinity binding of the radiolabeled complementary PNA probe In-111-/I-125-HP2 to Z(HER2:342)-SR-HP1 pre-treated cells was demonstrated. In-111-Z(HER2:342)-SR-HP1 demonstrated specific accumulation in SKOV-3 xenografts in BALB/C nu/nu mice and rapid clearance from blood. Pre-saturation of SKOV-3 with non-labeled anti-HER2 Affibody or the use of HER2-negative Ramos xenografts resulted in significantly lower tumor uptake of In-111-Z(HER2:342)-SR-HP1. The complementary PNA probe In-111/I-125-HP2 accumulated in SKOV-3 xenografts when Z(HER2:342)-SR-HP1 was injected 4 h earlier. The tumor accumulation of In-111/I-125-HP2 was negligible without Z(HER2:342)-SR-HP1 pre-injection. The uptake of In-111-HP2 in SKOV-3 xenografts was 19+/-2 % ID/g at 1 h after injection. The uptake in blood and kidneys was approximately 50- and 2-fold lower, respectively. In conclusion, we have shown that the use of Affibody-based PNA-mediated pretargeting enables specific delivery of radiometals to tumors and provides higher radiometal concentration in tumors than in kidneys.

Place, publisher, year, edition, pages
Ivyspring International Publisher , 2016. Vol. 6, no 1, 93-103 p.
Keyword [en]
Affibody, peptide nucleic acid, radionuclide pretargeting, scaffold protein, HER2
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:kth:diva-184565DOI: 10.7150/thno.12766ISI: 000371806600001PubMedID: 26722376ScopusID: 2-s2.0-84954489812OAI: oai:DiVA.org:kth-184565DiVA: diva2:916889
Funder
Swedish Cancer Society, 2012/354Swedish Research Council, 521-2012-2228, 621-2013-5135
Note

QC 20160405

Available from: 2016-04-05 Created: 2016-04-01 Last updated: 2016-04-05Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Westerlund, KristinaEriksson Karlström, Amelie
By organisation
Protein Technology
In the same journal
Theranostics
Immunology in the medical area

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: 26 hits
ReferencesLink to record
Permanent link

Direct link