The overexpression of gastrin-releasing peptide receptor (GRPR) in cancer can be used for peptide-receptor mediated radionuclide imaging and therapy. We have previously shown that an antagonist analog bombesin RM26 conjugated to 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) via a diethyleneglycol (PEG2) spacer (NOTA-PEG2-RM26) labeled with 68Ga GRPR-expressing tumors. In this study, we evaluated if variation mini-PEG length optimization targeting properties the NOTA-conjugated RM26....

Engineered affibody molecules can be used for high contrast in vivo molecular imaging. Extending a recombinantly produced HER2 binding molecule with hexa-histidine tag allows convenient purification by immobilized metal-ion affinity chromatography and labeling [99mTc(CO)3]+ but increases radioactivity uptake the liver. To investigate impact of charge, lipophilicity, position on biodistribution, 10 variants histidine-based was attached to molecule. The biochemical properties appeared similar...

Affibody molecules constitute a new class of probes for radionuclide tumor targeting. The small size is favorable rapid localization in tumors and clearance from circulation. However, high renal reabsorption prevents the use residualizing radiometals, including several promising low-energy β- α-emitters, therapy. We tested hypothesis that Affibody-based pretargeting mediated by bioorthogonal interaction between <i>trans</i>-cyclooctene (TCO) tetrazine would provide higher accumulation...

Affibody molecules are small proteins engineered using a nonantibody scaffold. Radiolabeled excellent imaging probes, but their application to radionuclide therapy has been prevented by high renal reabsorption. The aim of this study was test the hypothesis that Affibody-based peptide nucleic acid (PNA)–mediated pretargeted human epidermal growth factor receptor 2 (HER2)–expressing cancer extends survival without accompanying toxicity. <b>Methods:</b> A HER2-targeting molecule ligated with an...

Designed ankyrin repeat proteins (DARPins) are small engineered scaffold that can be selected for binding to desirable molecular targets. High affinity and size of DARPins render them promising probes radionuclide imaging. However, detailed knowledge on many factors influencing their imaging properties is still lacking. We have evaluated two human epidermal growth factor 2 (HER2)-specific with different properties. 9_29-H6 G3-H6 were radiolabeled iodine-125 tricarbonyl technetium-99m in...

Affibody molecules are a class of small (∼7 kDa) robust scaffold proteins suitable for radionuclide molecular imaging in vivo. The attachment hexahistidine (His6)-tag to the molecule allows facile purification by immobilized metal ion affinity chromatography (IMAC) but leads high accumulation radioactivity liver. Earlier, we have demonstrated that replacement His6-tag with negatively charged histidine–glutamate–histidine–glutamate–histidine–glutamate (HEHEHE)-tag permits IMAC, enables...

Accurate detection of cancer-associated molecular abnormalities in tumors could make cancer treatment more personalized. Affibody molecules enable high contrast imaging tumor-associated protein expression shortly after injection. The use the generator-produced positron-emitting radionuclide (68)Ga should increase sensitivity HER2 imaging. chemical nature radionuclides and chelators influences biodistribution molecules, providing an opportunity to further contrast. aim study was compare...

Gastrin‐releasing peptide receptors (GRPRs) are overexpressed in prostate cancer and suitable for targeted radionuclide therapy (TRT). We optimized the bombesin‐derived GRPR‐antagonist PEG 2 ‐RM26 labeling with 177 Lu further determined effect of treatment Lu‐labeled alone or combination anti‐HER2 antibody trastuzumab a murine model. The analog was coupled to NOTA, NODAGA, DOTA DOTAGA chelators. peptide‐chelator conjugates were labeled characterized vitro vivo . A preclinical therapeutic...

High expression of human epidermal growth factor receptor 2 (HER2) in breast and gastroesophageal carcinomas is a predictive biomarker for treatment using HER2-targeted therapeutics (antibodies trastuzumab pertuzumab, antibody-drug conjugate DM1, tyrosine kinase inhibitor lapatinib). Radionuclide molecular imaging HER2 might permit stratification patients HER2-targeting therapies. In this study, we evaluated new HER2-imaging probe based on the designed ankyrin repeat protein (DARPin) 9_29....

Affibody molecules (6-7 kDa) are a new class of small robust three-helical scaffold proteins. Radiolabeled subnanomolar anti-HER2 affibody ZHER2:342 was developed for imaging HER2 expression in tumors, and clinical study has demonstrated that the (111)In- (68)Ga-labeled can efficiently detect expressing metastases breast cancer patients. However, significant renal accumulation radioactivity after systemic injection radiolabeled conjugate is observed. The aim this to investigate mechanism...

Carbonic anhydrase IX (CAIX) is a transmembrane enzyme involved in regulation of tissue pH balance. In cancer, CAIX expression associated with tumor hypoxia. also overexpressed renal cell carcinoma and molecular target for the therapeutic antibody cG250 (girentuximab). Radionuclide imaging might be used identification patients who may benefit from therapy treatment strategies hypoxic tumors. Affibody molecules are small (7 kDa) scaffold proteins having high potential as probes radionuclide...

Visualization of cancer-associated alterations molecular phenotype using radionuclide imaging is a noninvasive approach to stratifying patients for targeted therapies. The engineered albumin-binding domain-derived affinity protein (ADAPT) promising tracer because its small size (6.5 kDa), which satisfies the precondition efficient tumor penetration and rapid clearance. Previous studies demonstrated that human epidermal growth factor receptor type 2 (HER2)-targeting ADAPT6 labeled with...

Affibody molecules are a class of affinity agents for molecular imaging based on non-immunoglobulin protein scaffold. Previous studies have demonstrated high contrast in vivo cancer-associated abnormalities using molecules. Using the radionuclide 18F labeling and PET as modality, sensitivity can be further increased. The use oxime formation between an aminooxy-functionalized peptide 18F-fluorobenzaldehyde (18F-FBA) is promising way radiolabeling targeting peptides. However, previous that...

Overexpression of human epidermal growth factor receptor type 3 (HER3) is associated with tumour cell resistance to HER-targeted therapies. Monoclonal antibodies (mAbs) targeting HER3 are currently being investigated for treatment various types cancers. Cumulative evidence suggests that affibody molecules may be appropriate alternatives mAbs. We previously reported a fusion construct (3A3) containing two HER3-targeting flanking an engineered albumin-binding domain (ABD035) included the...

Targeted delivery of toxins is a promising way to treat disseminated cancer. The use monoclonal antibodies as targeting moiety has provided proof-of-principle for this approach. However, extravasation and tissue penetration rates antibody-based immunotoxins are limited due antibody bulkiness. novel class probes, Affibody molecules, provides smaller toxin-conjugated constructs, which may improve targeting. Earlier, we have demonstrated that affitoxins containing HER2-targeting deimmunized...

Abstract Background Designed ankyrin repeat proteins (DARPins) are small engineered scaffold (14–18 kDa) that demonstrated promising tumor-targeting properties in preclinical studies. However, high renal accumulation of activity for DARPins labeled with residualizing labels is a limitation targeted radionuclide therapy. A better understanding the mechanisms behind kidney uptake could aid development strategies to reduce it. In this study, we have investigated whether [ 99m Tc]Tc(CO) 3 -G3...

Epithelial cell adhesion molecule (EpCAM) is overexpressed in 55%–75% of ovarian carcinomas (OC). EpCAM might be used as a target for treatment disseminated OC. Designed ankyrin repeats protein (DARPin) Ec1 small (18 kDa) protein, which binds to with subnanomolar affinity. We tested hypothesis that labeled non-residualizing label serve companion imaging diagnostic stratification patients EpCAM-targeting therapy. was 125I using N-succinimidyl-para-iodobenzoate. Binding affinity, specificity,...

Overexpression of insulin-like growth factor-1 receptor (IGF-1R) in several cancers is associated with resistance to therapy. Radionuclide molecular imaging IGF-1R expression tumors may help selecting the patients that will potentially respond IGF-1R-targeted Affibody molecules are small (7 kDa) non-immunoglobulin-based scaffold proteins well-suited probes for radionuclide imaging. The aim this study was evaluation an anti-IGF-1R affibody molecule labeled technetium-99m using...

Affibody molecules are small (7 kDa) nonimmunoglobulin scaffold proteins with favorable tumor-targeting properties. Studies concerning the influence of chelators on biodistribution ^99mTc-labeled demonstrated that variant a C-terminal glycyl-glycyl-glycyl-cysteine peptide–based chelator (designated Z_HER2:V2) has best profile in vivo and lowest renal retention radioactivity. The aim this study was to evaluate ¹⁸⁸Re-Z_HER2:V2 as potential candidate for...