[99mTc(CO)3]+-(HE)3-ZIGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours

Orlova, Anna; Hofström, Camilla; Strand, Joanna; Varasteh, Zohreh; Sandström, Mattias; Andersson, Karl; Tolmachev, Vladimir; Gräslund, Torbjörn

doi:10.1007/s00259-012-2284-8

Cited by 40 publications

(58 citation statements)

References 39 publications

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“…HER2 [38], HER1 [18], IGF-1R [19], PDGFRβ [39]), and is, probably, a property of this scaffold. Radioactivity accumulation in kidneys was not reduced with time, which reflected residualising properties of the label and was in agreement with previous observations for small proteins labeled using 99m Tc(CO) 3 [37,40]. Hepatocytes and bile duct cells in liver and glandular cells in intestine walls have medium HER3 expression (http://www.proteinatlas.org).…”

Section: In Vivo Comparison Of Biodistribution Of New (Hehehe-tagged)supporting

confidence: 91%

Imaging of HER3-expressing xenografts in mice using a 99mTc(CO)3-HEHEHE-ZHER3:08699 affibody molecule

Orlova

Malm

Rosestedt

et al. 2014

Eur J Nucl Med Mol Imaging

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Imaging of HER3-expressing xenografts in mice using a (99m)Tc(CO) 3-HEHEHE-Z HER3 08699 affibody molecule. Tc(CO) 3 -HEHEHE-Z 08699 was studied over time in mice bearing HER3-expressing xenografts. European Journal of Nuclear Medicine and MolecularResults. HEHEHE-Z 08699 was labeled with 99m Tc(CO) 3 with an isolated yield of >80% and a purity of >99%. Binding of 99m Tc(CO) 3 -HEHEHE-Z 08699 was specific to BT474 and MCF7 (breast cancer), and LS174T (colon cancer) cells. Cellular processing showed rapid binding and relatively quick internalization of receptor/affibody molecule complex (70% cell associated radioactivity was internalized after 24 h). Tumor targeting was receptor mediated and the excretion was predominantly renal. Receptor mediated uptake was also found in liver, lung, stomach, intestine, and salivary glands.At 4 h pi, tumor-to-blood ratios were 7±3 for BT474, and 6±2 for LS174T xenografts. LS174T tumors were visualized by microSPECT 4 h pi. Conclusions. The results of this study suggest feasibility of HER3-imaging in malignant tumors using affibody molecules.

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Section: In Vivo Comparison Of Biodistribution Of New (Hehehe-tagged)supporting

confidence: 91%

Imaging of HER3-expressing xenografts in mice using a 99mTc(CO)3-HEHEHE-ZHER3:08699 affibody molecule

Orlova

Malm

Rosestedt

et al. 2014

Eur J Nucl Med Mol Imaging

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“…There has been controversy over the role of ERβ2 in certain cancers, for example a number of studies have reported that E2 may promote lung adenocarcinoma development as well as insulin-like growth factor type-1 (3,4,7,8). This study demonstrated a potentially protective effect of ERβ2 in NSCLC, but showed that this effect did not persist, and indeed, was reversed, in the absence of IL-12Rβ2.…”

Section: Erβ2 Inhibits Nsclc Progression Via Il-12rβ2contrasting

confidence: 41%

“…Owing to its complex tumorigenesis, lung adenocarcinoma is difficult to treat and its course in individual patients is hard to predict. In order to identify therapeutic targets and prognostic biomarkers, research on lung adenocarcinoma has focused on a number of key molecules, in particular, certain growth factor receptors, such as epidermal growth factor receptor and insulin-like growth factor 1 receptor (3,4). Recent studies have reported that binding of estrogen to estrogen receptors (ERs) in NSCLC may affect progression of this disease, thus offering a potential target for treatment (5,6).…”

Section: Introductionmentioning

confidence: 99%

Estrogen receptorβ2 regulates interlukin-12 receptorβ2 expression via p38 mitogen-activated protein kinase signaling and inhibits non-small-cell lung cancer proliferation and invasion

Liu

Jiao

Chen

et al. 2012

Molecular Medicine Reports

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Abstract. Lung cancer is one of the most common types of cancer and is the leading cause of cancer-related mortality worldwide. Estrogens are known to be involved in the development and progression of non-small-cell lung cancer (NSCLC). These effects are initially mediated through binding of estrogen to estrogen receptors (ERs), in particular ERβ2. Our preliminary studies demonstrated that ERβ2 and interleukin-12 receptorβ2 (IL-12Rβ2) expression are correlated in NSCLC. The present study investigated the expression of these proteins in NSCLC cells and how changes in their expression affected cell proliferation and invasion. In addition, it aimed to explore whether p38 mitogen-activated protein kinase (p38MAPK) is involved in the regulation of IL-12Rβ2 expression by ERβ2. An immunocytochemical array was used to observe the distribution of ERβ2 and IL-12Rβ2. Co-immuoprecipitation was employed to observe the interaction between p38MAPK and IL-12Rβ2, by varying the expression of ERβ2 and p38MAPK. Western-blot analysis and reverse transcription-polymerase chain reaction assays were used to investigate the mechanism underlying ERβ2 regulation of IL-12Rβ2 expression. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, scratch wound healing and Transwell assays were used to investigate the impact of ERβ2 on proliferative, invasive and migratory abilities of NSCLC cells. ERβ2 was predominantly found in the cytoplasm and nucleus, whilst IL-12Rβ2 was largely confined to the cytoplasm, although a degree of expression was observed in the nucleus. Compared with normal bronchial epithelial cells, IL-12Rβ2 and ERβ2 were overexpressed in the NSCLC cell groups. Coimmuoprecipitation demonstrated an interaction between p38MAPK and IL-12Rβ2. ERβ2 appeared to upregulate IL-12Rβ2 expression and inhibition of p38MAPK attenuated this effect. ERβ2 and IL-12Rβ2 expression inhibited the proliferation, metastasis and invasion of NSCLC cell lines, but knockout of IL-12Rβ2, even in the presence of ERβ2, led to an increase in NSCLC cell proliferation and invasiveness. In conclusion, to the best of our knowledge this study is the first to demonstrate that IL-12Rβ2 may be important in the mechanisms underlying ERβ2 inhibition of NSCLC development, and that this interaction may be mediated via p38MAPK. IntroductionNon-small-cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide (1). Lung adenocarcinoma is the most common form of NSCLC (1,2). Owing to its complex tumorigenesis, lung adenocarcinoma is difficult to treat and its course in individual patients is hard to predict. In order to identify therapeutic targets and prognostic biomarkers, research on lung adenocarcinoma has focused on a number of key molecules, in particular, certain growth factor receptors, such as epidermal growth factor receptor and insulin-like growth factor 1 receptor (3,4). Recent studies have reported that binding of estrogen to estrogen receptors (ERs) in NSCLC may affect progression of this disease, thus offering a potential targ...

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“…The use of pretargeting is favorable for ESPs, because these agents are often slowly internalized by malignant cells and clear rapidly, within a few hours, from the blood (9,(12)(13)(14). This ensures that a large number of recognition tags would remain on the surface of pretargeted malignant cells at the time of injection of the radiolabeled secondary agent.…”

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confidence: 99%

“…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).…”

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confidence: 99%

Feasibility of Affibody-Based Bioorthogonal Chemistry–Mediated Radionuclide Pretargeting

et al. 2015

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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...

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[99mTc(CO)3]+-(HE)3-ZIGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours

Cited by 40 publications

References 39 publications

Imaging of HER3-expressing xenografts in mice using a 99mTc(CO)3-HEHEHE-ZHER3:08699 affibody molecule

Imaging of HER3-expressing xenografts in mice using a 99mTc(CO)3-HEHEHE-ZHER3:08699 affibody molecule

Estrogen receptorβ2 regulates interlukin-12 receptorβ2 expression via p38 mitogen-activated protein kinase signaling and inhibits non-small-cell lung cancer proliferation and invasion

Feasibility of Affibody-Based Bioorthogonal Chemistry–Mediated Radionuclide Pretargeting

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