Designed ankyrin repeat proteins (DARPins) are small engineered scaffold proteins that can be selected for binding to desirable molecular targets. High affinity and small size of DARPins render them promising probes for radionuclide molecular 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 DARPins with different size and binding properties. DARPins 9_29-H 6 and G3-H 6 were radiolabeled with iodine-125 and tricarbonyl technetium-99m and evaluated in vitro. A side-by-side comparison of biodistribution and tumor targeting was performed. HER2-specific tumor accumulation of G3-H 6 was demonstrated. A combination of smaller size and higher affinity resulted in a higher tumor uptake of G3-H 6 in comparison to 9_29-H 6 . Technetium-99m labeled G3-H 6 demonstrated a better biodistribution profile than 9_29-H 6 , with several-fold lower uptake in liver. Radioiodinated G3-H 6 showed the best tumor-to-organ ratios. The combined effect of affinity, molecular weight, scaffold composition, and nonresidualizing properties of iodine label provided radioiodinated G3-H 6 with high clinical potential for imaging of HER2.

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 and pertuzumab, antibody-drug conjugate trastuzumab DM1, and tyrosine kinase inhibitor lapatinib). Radionuclide molecular imaging of HER2 expression might permit stratification of patients for HER2-targeting therapies. In this study, we evaluated a new HER2-imaging probe based on the designed ankyrin repeat protein (DARPin) 9_29. DARPin 9_29 was labeled with iodine-125 by direct radioiodination and with [99mTc]Tc(CO)3 using the C-terminal hexahistidine tag. DARPin 9_29 preserved high specificity and affinity of binding to HER2-expressing cells after labeling. Uptake of [125I]I-DARPin 9_29 and [99mTc]Tc(CO)3-DARPin 9_29 in HER2-positive SKOV-3 xenografts in mice at 6 h after injection was 3.4 ± 0.7 %ID/g and 2.9 ± 0.7 %ID/g, respectively. This was significantly (p < 0.00005) higher than the uptake of the same probes in HER2-negative Ramos lymphoma xenografts, 0.22 ± 0.09 %ID/g and 0.30 ± 0.05 %ID/g, respectively. Retention of [125I]I-DARPin 9_29 in the lung, liver, spleen, and kidneys was appreciably lower compared with [99mTc]Tc(CO)3-DARPin 9_29, which resulted in significantly (p < 0.05) higher tumor-to-organ ratios. The biodistribution data were confirmed by SPECT/CT imaging. In conclusion, radioiodine is a preferable label for DARPin 9_29.

Patients with atrial fibrillation and rapid ventricular rates refractory to medical treatment have marked signs of brain hypoperfusion and impaired CF. Ablation and pacing improve left ventricular systolic function, thereby increasing BP and improving CF.

The coronary revascularization on beating heart or preventive administration of instenon in CPB patients helps significantly to diminish the risk of cerebrovascular complication.

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SUMMARYAims: To investigate the regional cerebral blood flow, cognitive function, and parameters of 24-h arterial blood pressure monitoring in patients with metabolic syndrome before and after combination antihypertensive therapy. Methods: The study involved 54 patients with metabolic syndrome (MetS) investigated by brain single-photon emission computed tomography, 24-h blood pressure monitoring (ABPM), and comprehensive neuropsychological testing before and after 24 weeks of combination antihypertensive therapy. Results: Patients with metabolic syndrome had significantly poorer regional cerebral blood flow compared with control group: by 7% (P = 0.003) in right anterior parietal cortex, by 6% (P = 0.028) in left anterior parietal cortex, by 8% (P = 0.007) in right superior frontal lobe, and by 10% (P = 0.00002) and 7% (P = 0.006) in right and left temporal brain regions, correspondingly. The results of neuropsychological testing showed 11% decrease in mentation (P = 0.002), and 19% (P = 0.011) and 20% (P = 0.009) decrease in immediate verbal and visual memory in patients with MetS as compared with control group. Relationships between the indices of ABPM, cerebral perfusion, and cognitive function were found. Data showed an improvement of regional cerebral blood flow, ABPM parameters, and indicators of cognitive functions after 6 months of antihypertensive therapy in patients with MetS. Conclusion: The study showed the presence of diffuse disturbances in cerebral perfusion is associated with cognitive disorders in patients with metabolic syndrome. Combination antihypertensive treatment exerts beneficial effects on the 24-h blood pressure profile, increases cerebral blood flow, and improves cognitive function in patients with MetS.

Introduction. The purpose of this study was to evaluate the feasibility of using 99mTc-TG SPECT in the detection and staging of malignant lymphoma.Materials and methods.Fifteen patients with newly diagnosed malignant lymphoma  underwent 99mTc-TG SPECT. Six patients had Hodgkin’s lymphoma and 9 patients had aggressive forms of non-Hodgkin’s lymphoma (NHL): diffuse large B-cell lymphoma (7  cases), B-cell follicular lymphoma (1 case), and lymphoma from B cells in the marginal zone  (1 case). Stage IIA was diagnosed in 5 patients, stage IIB in 1, stage IIIA in 1, stage IVA in 4 and stage IVB in 4 patients.Results.Pathological 99mTc-TG uptake in lymph nodes was observed in 14 (93 %) of the  15 patients. In one patient, the enlarged submandibular lymph node (16 mm in size)  detected by CT was not visualized by 99mTc-TG SPECT. This false-negative result was likely  to be associated with increased accumulation of 99mTc-TG in the oropharyngeal region.  There were difficulties in the visualization of paratracheal, para-aortic and paracardial lymph  nodes. These difficulties were associated with a high blood background activity, which  persisted even 4 hours after intravenous injection of 99mTc-TG. Software-based SPECT and  CT image fusion allowed visualization of these lymph nodes. The pathological 99mTc-TG  accumulation in axillary, supraclavicular, infraclavicular and cervical lymph nodes was  observed most often. Extranodal involvement was seen in 9 patients. 99mTc-TG SPECT identified extranodal hypermetabolic lesions in 7 (78 %) of these patients. In one  patient, hypermetabolic lesion in the lung detected by 99mTc-TG SPECT was not detected on CT image. CT identified bone marrow involvement in the pelvic and scapula in 1 patient. The  use of 99mTc-TG SPECT allowed the visualization of hypermetabolic bone tissue lesions  in this patient (Figure 4). In addition, in a patient with intact bone tissue on CT, 99mTc-TG SPECT detected hypermetabolic lesions in the iliac bone.Conclusion.99mTc-1-Thio-D-glucose demonstrated increased uptake in nodal and  extranodal sites of lymphoma. The results indicate that SPECT with 99mTc-1-Thio-D-glucose is a feasible and useful tool in the detection and staging malignant lymphoma.