Evaluation of 99mTc-ZIGF1R:4551-GGGC affibody molecule, a new probe for imaging of insulin-like growth factor type 1 receptor expression

Mitran, Bogdan; Altai, Mohamed; Hofström, Camilla; Honarvar, Hadis; Sandström, Mattias; Orlova, Anna; Tolmachev, Vladimir; Gräslund, Torbjörn

doi:10.1007/s00726-014-1859-z

Cited by 22 publications

(24 citation statements)

References 46 publications

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“…This indicated that the main reason of the release was re-oxidation of technetium. This was not what we have observed earlier for anti-HER2 and anti-IGF-1R affibody molecules, where even -GGGC provided a stable attachment of 99m Tc and 188 Re (Wållberg et al 2011; Altai et al 2012, 2014a, b; Mitran et al 2015). A possible explanation for the current results is that some side chains in the affibody molecules form an alternative chelating pocket and a part of technetium is bound not only to a cysteine-containing chelator, but also to this much weaker site.…”

Section: Discussioncontrasting

confidence: 66%

Influence of composition of cysteine-containing peptide-based chelators on biodistribution of 99mTc-labeled anti-EGFR affibody molecules

et al. 2018

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Epidermal growth factor receptor (EGFR) is overexpressed in a number of cancers and is the molecular target for several anti-cancer therapeutics. Radionuclide molecular imaging of EGFR expression should enable personalization of anti-cancer treatment. Affibody molecule is a promising type of high-affinity imaging probes based on a non-immunoglobulin scaffold. A series of derivatives of the anti-EGFR affibody molecule ZEGFR:2377, having peptide-based cysteine-containing chelators for conjugation of 99mTc, was designed and evaluated. It was found that glutamate-containing chelators Gly-Gly-Glu-Cys (GGEC), Gly-Glu-Glu-Cys (GEEC) and Glu-Glu-Glu-Cys (EEEC) provide the best labeling stability. The glutamate containing conjugates bound to EGFR-expressing cells specifically and with high affinity. Specific targeting of EGFR-expressing xenografts in mice was demonstrated. The number of glutamate residues in the chelator had strong influence on biodistribution of radiolabeled affibody molecules. Increase of glutamate content was associated with lower uptake in normal tissues. The 99mTc-labeled variant containing the EEEC chelator provided the highest tumor-to-organ ratios. In conclusion, optimizing the composition of peptide-based chelators enhances contrast of imaging of EGFR-expression using affibody molecules.Electronic supplementary materialThe online version of this article (10.1007/s00726-018-2571-1) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 66%

Influence of composition of cysteine-containing peptide-based chelators on biodistribution of 99mTc-labeled anti-EGFR affibody molecules

et al. 2018

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“…Because of their small size, affibody can be synthesized or recombinantly expressed. Since the first construct HER2-targeting affibody molecule Z HER2:342 was produced and confirmed to bind to HER2-positive cancer cell lines [24], several similar affibody molecules targeting EGFR [23,24], HER3 [27,28], IGF-1R [42], HIV-1-gp120 [43] and HPV16E7 [30,31] have been reported and also applied to image several tumour-associated molecular targets, such as HER2 [25,44], EGFR [45,46], HER3 [47]. The first clinical imaging study on patients with breast cancer was conducted using HER2-specific affibody, which Mice bearing C666-1tumor grafts were intravenously injected with 100 nmol/kg Z142X, Z142, or an equal amount of control agents or the same volume of PBS every two days for 15 times via tail vein.…”

Section: Discussionmentioning

confidence: 99%

Novel EBV LMP-2-affibody and affitoxin in molecular imaging and targeted therapy of nasopharyngeal carcinoma

et al. 2020

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Epstein-Barr virus (EBV) infection is closely linked to several human malignancies including endemic Burkitt's lymphoma, Hodgkin's lymphoma and nasopharyngeal carcinomas (NPC). Latent membrane protein 2 (LMP-2) of EBV plays a pivotal role in pathogenesis of EBVrelated tumors and thus, is a potential target for diagnosis and targeted therapy of EBV LMP-2 + malignant cancers. Affibody molecules are developing as imaging probes and tumor-targeted delivery of small molecules. In this study, four EBV LMP-2-binding affibodies (Z EBV LMP-2 12, Z EBV LMP-2 132, Z EBV LMP-2 137, and Z EBV LMP-2 142) were identified by screening a phage-displayed LMP-2 peptide library for molecular imaging and targeted therapy in EBV xenograft mice model. Z EBV LMP-2 affibody has high binding affinity for EBV LMP-2 and accumulates in mouse tumor derived from EBV LMP-2 + xenografts for 24 h after intravenous (IV) injection. Subsequent fusion of Pseudomonas exotoxin PE38KDEL to the Z EBV LMP-2 142 affibody led to production of Z142X affitoxin. This fused Z142X affitoxin exhibits high cytotoxicity specific for EBV + cells in vitro and significant antitumor effect in mice bearing EBV + tumor xenografts by IV injection. The data provide the proof of principle that EBV LMP-2-speicifc affibody molecules are useful for molecular imaging diagnosis and have potentials for targeted therapy of LMP-2-expressing EBV malignancies.

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“…Moreover, preclinical studies demonstrated feasibility of application of affibody molecules for imaging several molecular targets in cancer xenografts, e.g. EGFR (33), HER3 (48) IGF-1R (49), PDGFRβ (50) and CAIX (51). It would be attractive to apply our experience in development of HER2-imaging affibody molecule probes for development of probes to new targets.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of imaging of epidermal growth factor receptor expression with ZEGFR:2377 affibody molecule labeled with 99mTc using a peptide-based cysteine-containing chelator

Andersson

Oroujeni

Garousi

et al. 2016

International Journal of Oncology

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The epidermal growth factor receptor (EGFR) is overexpressed in a number of malignant tumors and is a molecular target for several specific anticancer antibodies and tyrosine kinase inhibitors. The overexpression of EGFR is a predictive biomarker for response to several therapy regimens. Radionuclide molecular imaging might enable detection of EGFR overexpression by a non-invasive procedure and could be used repeatedly. Affibody molecules are engineered scaffold proteins, which could be selected to have a high affinity and selectivity to predetermined targets. The anti-EGFR ZEGFR:2377 affibody molecule is a potential imaging probe for EGFR detection. The use of the generator-produced radionuclide 99mTc should facilitate clinical translation of an imaging probe due to its low price, availability and favorable dosimetry of the radionuclide. In the present study, we evaluated feasibility of ZEGFR:2377 labeling with 99mTc using a peptide-based cysteine-containing chelator expressed at the C-terminus of ZEGFR:2377. The label was stable in vitro under cysteine challenge. In addition, 99mTc-ZEGFR:2377 was capable of specific binding to EGFR-expressing cells with high affinity (274 pM). Studies in BALB/C nu/nu mice bearing A431 xenografts demonstrated that 99mTc-ZEGFR:2377 accumulates in tumors in an EGFR-specific manner. The tumor uptake values were 3.6±1 and 2.5±0.4% ID/g at 3 and 24 h after injection, respectively. The corresponding tumor-to-blood ratios were 1.8±0.4 and 8±3. The xenografts were clearly visualized at both time-points. This study demonstrated the potential of 99mTc-labeled ZEGFR:2377 for imaging of EGFR in vivo.

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Evaluation of 99mTc-ZIGF1R:4551-GGGC affibody molecule, a new probe for imaging of insulin-like growth factor type 1 receptor expression

Cited by 22 publications

References 46 publications

Influence of composition of cysteine-containing peptide-based chelators on biodistribution of 99mTc-labeled anti-EGFR affibody molecules

Influence of composition of cysteine-containing peptide-based chelators on biodistribution of 99mTc-labeled anti-EGFR affibody molecules

Novel EBV LMP-2-affibody and affitoxin in molecular imaging and targeted therapy of nasopharyngeal carcinoma

Feasibility of imaging of epidermal growth factor receptor expression with ZEGFR:2377 affibody molecule labeled with 99mTc using a peptide-based cysteine-containing chelator

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