Evaluation of the Radiocobalt-Labeled [MMA-DOTA-Cys61]-ZHER2:2395-Cys Affibody Molecule for Targeting of HER2-Expressing Tumors

Wållberg, Helena; Ahlgren, Sara; Widström, Charles; Orlova, Anna

doi:10.1007/s11307-009-0238-8

Cited by 30 publications

(69 citation statements)

References 26 publications

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“…A strong influence of a radiometal/chelator combination on imaging contrast has been observed also for Affibody molecules. For example, biodistribution and tumour-to-organ ratios of DOTA-conjugated anti-HER2 Affibody molecules were altered appreciably by substitution of 68 Ga by 111 In or 44 Sc and by substitution of 111 In by 57 Co 23–25 . Importantly, systematic studies concerning influence of radionuclides on biodistribution of tumour-targeting Affibody conjugates might help to select a probe with the optimal imaging characteristics.…”

Section: Introductionmentioning

confidence: 99%

“…55 Co can be produced by the 54 Fe( d , n ) 55 Co reaction on enriched 54 Fe targets using low-energy cyclotrons available at PET-centres 26, 30 . Importantly, the DOTA chelator provides stable coupling of radiocobalt to targeting proteins and peptides 22, 25, 26, 28 . The use of a positron-emitting label for DOTA-ZEGFR:2377 would further improve detection of EGFR expression in vivo , since PET provides better imaging sensitivity compared with SPECT.…”

Section: Introductionmentioning

confidence: 99%

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The use of radiocobalt as a label improves imaging of EGFR using DOTA-conjugated Affibody molecule

Garousi

Andersson

Dam

et al. 2017

Sci Rep

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Several anti-cancer therapies target the epidermal growth factor receptor (EGFR). Radionuclide imaging of EGFR expression in tumours may aid in selection of optimal cancer therapy. The 111In-labelled DOTA-conjugated ZEGFR:2377 Affibody molecule was successfully used for imaging of EGFR-expressing xenografts in mice. An optimal combination of radionuclide, chelator and targeting protein may further improve the contrast of radionuclide imaging. The aim of this study was to evaluate the targeting properties of radiocobalt-labelled DOTA-ZEGFR:2377. DOTA-ZEGFR:2377 was labelled with 57Co (T1/2 = 271.8 d), 55Co (T1/2 = 17.5 h), and, for comparison, with the positron-emitting radionuclide 68Ga (T1/2 = 67.6 min) with preserved specificity of binding to EGFR-expressing A431 cells. The long-lived cobalt radioisotope 57Co was used in animal studies. Both 57Co-DOTA-ZEGFR:2377 and 68Ga-DOTA-ZEGFR:2377 demonstrated EGFR-specific accumulation in A431 xenografts and EGFR-expressing tissues in mice. Tumour-to-organ ratios for the radiocobalt-labelled DOTA-ZEGFR:2377 were significantly higher than for the gallium-labelled counterpart already at 3 h after injection. Importantly, 57Co-DOTA-ZEGFR:2377 demonstrated a tumour-to-liver ratio of 3, which is 7-fold higher than the tumour-to-liver ratio for 68Ga-DOTA-ZEGFR:2377. The results of this study suggest that the positron-emitting cobalt isotope 55Co would be an optimal label for DOTA-ZEGFR:2377 and further development should concentrate on this radionuclide as a label.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The use of radiocobalt as a label improves imaging of EGFR using DOTA-conjugated Affibody molecule

Garousi

Andersson

Dam

et al. 2017

Sci Rep

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“…Affibody molecules are engineered non-immunogenic small proteins with 58-amino acid residues (~7 kDa) and a 3-helix bundle structure (Nygren 2008; Nygren and Skerra 2004; Tolmachev et al 2007a). HER2-binding Affibody molecules with picomolar affinity have been identified and investigated as therapeutic and imaging agents for HER2-overexpressing malignant tumors (Orlova et al 2009; McLarty et al 2009b; Kramer-Marek et al 2009; Wallberg et al 2009; Tran et al 2007; Tolmachev et al 2006, 2009; Orlova et al 2006; Cheng et al 2008; Ahlgren et al 2009). In our previous studies, we have found that of the various anti- HER2 Affibody protein constructs available (monomeric vs. dimeric), the smaller ones performed substantially better in vivo in terms of tumor uptake as well as better clearance (Cheng et al 2008).…”

Section: Introductionmentioning

confidence: 99%

In vivo targeting of HER2-positive tumor using 2-helix affibody molecules

et al. 2011

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Molecular imaging of human epidermal growth factor receptor type 2 (HER2) expression has drawn significant attention because of the unique role of the HER2 gene in diagnosis, therapy and prognosis of human breast cancer. In our previous research, a novel cyclic 2-helix small protein, MUT-DS, was discovered as an anti-HER2 Affibody analog with high affinity through rational protein design and engineering. MUT-DS was then evaluated for positron emission tomography (PET) of HER2-positive tumor by labeling with two radionuclides, 68Ga and 18F, with relatively short half-life (t1/2 < 2 h). In order to fully study the in vivo behavior of 2-helix small protein and demonstrate that it could be a robust platform for labeling with a variety of radionuclides for different applications, in this study, MUT-DS was further radiolabeled with 64Cu or 111In and evaluated for in vivo targeting of HER2-positive tumor in mice. Design 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (DOTA) conjugated MUT-DS (DOTA–MUT-DS) was chemically synthesized using solid phase peptide synthesizer and I2 oxidation. DOTA–MUTDS was then radiolabeled with 64Cu or 111In to prepare the HER2 imaging probe (64Cu/111In-DOTA–MUT-DS). Both biodistribution and microPET imaging of the probe were evaluated in nude mice bearing subcutaneous HER2-positive SKOV3 tumors. DOTA–MUT-DS could be successfully synthesized and radiolabeled with 64Cu or 111In. Biodistribution study showed that tumor uptake value of 64Cu or 111In-labeled DOTA–MUT-DS was 4.66 ± 0.38 or 2.17 ± 0.15%ID/g, respectively, in nude mice bearing SKOV3 xenografts (n = 3) at 1 h post-injection (p.i.). Tumor-to-blood and tumor-to-muscle ratios for 64Cu-DOTA-MUT-DS were attained to be 3.05 and 3.48 at 1 h p.i., respectively, while for 111In-DOTA–MUT-DS, they were 2.04 and 3.19, respectively. Co-injection of the cold Affibody molecule ZHER2:342 with 64Cu-DOTA-MUT-DS specifically reduced the SKOV3 tumor uptake of the probe by 48%. 111In-DOTA–MUT-DS displayed lower liver uptake at all the time points investigated and higher tumor to blood ratios at 4 and 20 h p.i., when compared with 64Cu-DOTA–MUT-DS. This study demonstrates that the 2-helix protein based probes, 64Cu/111In DOTA–MUT-DS, are promising molecular probes for imaging HER2-positive tumor. Two-helix small protein scaffold holds great promise as a novel and robust platform for imaging and therapy applications.

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“…Cobalt-55 ( t 1/2 = 17.53 h, 76% β + , E max = 1498 keV) is an intermediate-lived positron-emitting radionuclide that is a useful radiotracer for positron emission tomography (PET) (De Reuck et al, 2004, 1999; Jansen et al, 1997a, 1997b, 1994, 1996b, 1995; Korf et al, 1998; Stevens et al, 1999) and particularly useful for labeling proteins due to its favorable complexation with established bifunctional chelators (Dam et al, 2016; Garousi et al, 2017; Mastren et al, 2015; Srivastava et al, 1994; Thisgaard et al, 2011b; Wallberg et al, 2010). Furthermore, when chelated in oxidation state 3+, the formed complex is considered inert (Duckworth et al, 2009; Regoeczi et al, 1995; Wegner and Spatz, 2013) and therefore it is less prone to interact with ligands in blood plasma and non-targeted organs due to trans-chelation.…”

Section: Introductionmentioning

confidence: 99%

“…So far, only seven studies have followed this chelator-based approach (Dam et al, 2016; Garousi et al, 2017; Goethals et al, 2000; Mastren et al, 2015; Srivastava et al, 1994; Thisgaard et al, 2011b; Wallberg et al, 2010). Goethals et al (Goethals et al, 2000) labeled 55 Co to ethylene diamine tetraacetic acid (EDTA) and characterized this complex for the application in the measurement of the glomerular filtration rate in kidneys via PET, a study which is commonly performed with the perfusion tracer 51 Cr-EDTA (Chantler et al, 1969).…”

Section: Introductionmentioning

confidence: 99%

Cyclotron production and radiochemical separation of 55Co and 58mCo from 54Fe, 58Ni and 57Fe targets

Valdovinos

Hernandez

Graves

et al. 2017

Applied Radiation and Isotopes

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This work presents the production with a cyclotron of the positron emitter 55Co via the 54Fe(d,n) and 58Ni(p,α) reactions and the Auger electron emitter 58mCo via the 57Fe(d,n) reaction after high current (40 μA p and 60 μA d) irradiation on electroplated targets. High specific activity radionuclides (up to 55.6 GBq/μmol 55Co and 31.8 GBq/μmol 58mCo) with high radionuclidic purity (99.995% 55Co from 54Fe, 98.8% 55Co from 58Ni, and 98.7% 58mCo from 57Fe at end of bombardment, EoB), in high activity concentration (final separated radionuclide in < 0.6 mL) and with almost quantitative overall activity separation yield (> 92%) were obtained after processing of the irradiated targets with novel radiochemical separation methods based on HCl dissolution and the resin N,N,N′,N′-tetrakis-2-ethylhexyldiglycolamide (DGA, branched). One hour long irradiations using 38–65, 110–214 and 59–78 mg of enriched 54Fe (99.93%), 58Ni (99.48%) and 57Fe (95.06%), respectively, electroplated over a 1.0 cm2 surface, yielded 582 ± 66 MBq 55Co, 372 ± 14 MBq 55Co and 810 ± 186 MBq 58mCo, respectively, decay corrected to EoB. The separation methods allow for the recovery of the costly enriched target materials, which were reconstituted into metallic targets after novel electroplating methods, with an overall recycling efficiency of 93 ± 4% for iron. The produced radionuclides were used to radiolabel the angiogenesis marker antibody TRC105 conjugated to the chelator NOTA as a demonstration of their quality.

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Evaluation of the Radiocobalt-Labeled [MMA-DOTA-Cys61]-ZHER2:2395-Cys Affibody Molecule for Targeting of HER2-Expressing Tumors

Abstract: Radiocobalt is a promising label for affibody molecules for future PET applications.

Cited by 30 publications

References 26 publications

The use of radiocobalt as a label improves imaging of EGFR using DOTA-conjugated Affibody molecule

The use of radiocobalt as a label improves imaging of EGFR using DOTA-conjugated Affibody molecule

In vivo targeting of HER2-positive tumor using 2-helix affibody molecules

Cyclotron production and radiochemical separation of 55Co and 58mCo from 54Fe, 58Ni and 57Fe targets

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