186Re-maSGS-ZHER2:342, a potential Affibody conjugate for systemic therapy of HER2-expressing tumours

Orlova, Anna; Tran, Thuy; Ekblad, T.; Karlström, Amelie Eriksson; Tolmachev, Vladimir

doi:10.1007/s00259-009-1268-9

Cited by 38 publications

(27 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These factors can be used to optimize targeting properties. We demonstrated earlier that the 186 Re-maGSG-Z HER2:342 Affibody molecule, having an Nterminal mercaptoacetyl-glycyl-seryl-glycyl chelator, shows better retention of radioactivity in tumors than in kidneys (25). However, appreciable hepatobiliary excretion of 186 Re-maGSG-Z HER2:342 (20% of injected radioactivity was measured in the intestinal content at 4 h after injection) caused a risk of high absorbed dose to intestines.…”

Section: Discussionmentioning

confidence: 99%

“…We expected that substitution of 99m Tc for 188 Re in Affibody molecules might provide a conjugate with a high tumor uptake and low renal retention. However, the chemical properties of rhenium and technetium are similar but not identical, and biodistribution of 99m Tc-and 188 Re-labeled peptides can be different (24,25). Therefore, an evaluation of 188 Re-labeled Z HER2:V2 was necessary.…”

mentioning

confidence: 99%

See 1 more Smart Citation

¹⁸⁸Re-Z_HER2:V2, a Promising Affibody-Based Targeting Agent Against HER2-Expressing Tumors: Preclinical Assessment

et al. 2014

Self Cite

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

¹⁸⁸Re-Z_HER2:V2, a Promising Affibody-Based Targeting Agent Against HER2-Expressing Tumors: Preclinical Assessment

et al. 2014

Self Cite

View full text Add to dashboard Cite

“…In addition, different chemistry was used for conjugation of the DOTA chelator. Earlier experience with Affibody molecules has suggested that even smaller changes in composition (substitution of one to three amino acids) could cause appreciable differences in biodistribution, such as the level of hepatic uptake [25,26] or percentage of hepatobiliary excretion [27][28][29]. Moreover, coupling of different nuclides using the same chelator could cause differences in organ uptake and blood clearance rate of Affibody molecules [21,29,30].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of backbone-cyclized HER2-binding 2-helix Affibody molecule for In Vivo molecular imaging

Honarvar¹,

Jokilaakso²,

Andersson³

et al. 2013

Nuclear Medicine and Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Internalization of Affibody molecules by cancer cells is slow (12)(13)(14), and the residualizing properties of a radionuclide are not critical for good tumor retention. Internalization of Affibody molecules in proximal tubuli and the following proteolytic degradation is rapid; radiocatabolites of nonresidualizing labels (radioiodine and 186/188 Re in combination with some chelators) are cleared rapidly from the kidneys (15)(16)(17). This approach provided a residence time in tumors that was longer than in the kidneys.…”

mentioning

confidence: 89%

Feasibility of Affibody-Based Bioorthogonal Chemistry–Mediated Radionuclide Pretargeting

et al. 2015

Self Cite

View full text Add to dashboard Cite

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 β-and α-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 111 In and 177 Lu. 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: 125 I-Z 2395 -TCO bound specifically to HER2-expressing cells in vitro with an affinity of 45 ± 16 pM. 111 In-tetrazine bound specifically and selectively to Z 2395 -TCO pretreated cells. In vivo studies demonstrated HER2-specific 125 I-Z 2395 -TCO accumulation in xenografts. TCO-mediated 111 In-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 111 In-tetrazine and 177 Lu-tetrazine was approximately 2-fold higher than the renal uptake. Pretargeting provided more than a 56-fold reduction of renal uptake of 111 In in comparison with direct targeting. Conclusion: The feasibility of Affibody-based bioorthogonal chemistry-mediated pretargeting was demonstrated. The use of pretargeting provides a substantial reduction of radiometal accumulation in kidneys, creating preconditions for palliative radionuclide therapy. Radi onuclide targeting of tumor-specific overexpressed cell surface proteins has a potential to improve cancer therapy. Radionuclide imaging might help to identify patients with tumors expressing a particular target and therefore would be likely to respond to a particular therapy based on antibodies or tyrosine kinase inhibitors (1). Delivery of cytotoxic radionuclides (e.g., b-or a-emitters) might have strong palliative or even curative effects (2).Two classes of substances have commonly been exploited for radionuclide targeting: monoclonal antibodies (and their derivatives) and peptide ligands to receptors overexpressed in tumors. Engineered scaffold proteins (ESPs) constitute a new type of targeting agents for radionuclide tumor targeting (3). ESPs contain a robust framework providing conformational stability and variable surface amino acids. Randomization of variable amino acids enables selection of high-affinity binders to different proteins using molecular display technology. Several ESPs, such as Affibody (Affibody AB) molecules (4), designed ankyrin repeat proteins (5), fibronectin domains (6), anticalins (7), cysteine-knot peptides (8), and albu...

show abstract

186Re-maSGS-ZHER2:342, a potential Affibody conjugate for systemic therapy of HER2-expressing tumours

Abstract: Optimization of chelators improves biodistribution properties of rhenium-labelled small scaffold proteins and enables selection of promising radiotherapeutic agents based on the Affibody molecule.

Cited by 38 publications

References 32 publications

¹⁸⁸Re-Z_HER2:V2, a Promising Affibody-Based Targeting Agent Against HER2-Expressing Tumors: Preclinical Assessment

¹⁸⁸Re-Z_HER2:V2, a Promising Affibody-Based Targeting Agent Against HER2-Expressing Tumors: Preclinical Assessment

Evaluation of backbone-cyclized HER2-binding 2-helix Affibody molecule for In Vivo molecular imaging

Feasibility of Affibody-Based Bioorthogonal Chemistry–Mediated Radionuclide Pretargeting

Contact Info

Product

Resources

About

186Re-maSGS-ZHER2:342, a potential Affibody conjugate for systemic therapy of HER2-expressing tumours

Abstract: Optimization of chelators improves biodistribution properties of rhenium-labelled small scaffold proteins and enables selection of promising radiotherapeutic agents based on the Affibody molecule.

Cited by 38 publications

References 32 publications

188Re-ZHER2:V2, a Promising Affibody-Based Targeting Agent Against HER2-Expressing Tumors: Preclinical Assessment

188Re-ZHER2:V2, a Promising Affibody-Based Targeting Agent Against HER2-Expressing Tumors: Preclinical Assessment

Evaluation of backbone-cyclized HER2-binding 2-helix Affibody molecule for In Vivo molecular imaging

Feasibility of Affibody-Based Bioorthogonal Chemistry–Mediated Radionuclide Pretargeting

Contact Info

Product

Resources

About

¹⁸⁸Re-Z_HER2:V2, a Promising Affibody-Based Targeting Agent Against HER2-Expressing Tumors: Preclinical Assessment

¹⁸⁸Re-Z_HER2:V2, a Promising Affibody-Based Targeting Agent Against HER2-Expressing Tumors: Preclinical Assessment