One-Step (18)F-Labeling of Carbohydrate-Conjugated Octreotate-Derivatives Containing a Silicon-Fluoride-Acceptor (SiFA): In Vitro and in Vivo Evaluation as Tumor Imaging Agents for Positron Emission Tomography (PET)

The synthesis, radiolabeling, and initial evaluation of new silicon-fluoride acceptor (SiFA) derivatized octreotate derivatives is reported. So far, the main drawback of the SiFA technology for the synthesis of PET-radiotracers is the high lipophilicity of the resulting radiopharmaceutical. Consequently, we synthesized new SiFA-octreotate analogues derivatized with Fmoc-NH-PEG-COOH, Fmoc-Asn(Ac?AcNH-?-Glc)-OH, and SiFA-aldehyde (SIFA-A). The substances could be labeled in high yields (38 ± 4%) and specific activities between 29 and 56 GBq/?mol in short synthesis times of less than 30 min (e.o.b.). The in vitro evaluation of the synthesized conjugates displayed a sst2 receptor affinity (IC?? = 3.3 ± 0.3 nM) comparable to that of somatostatin-28. As a measure of lipophilicity of the conjugates, the log P(ow) was determined and found to be 0.96 for SiFA-Asn(AcNH-?-Glc)-PEG-Tyr³-octreotate and 1.23 for SiFA-Asn(AcNH-?-Glc)-Tyr³-octreotate, which is considerably lower than for SiFA-Tyr³-octreotate (log P(ow) = 1.59). The initial in vivo evaluation of [¹?F]SiFA-Asn(AcNH-?-Glc)-PEG-Tyr³-octreotate revealed a significant uptake of radiotracer in the tumor tissue of AR42J tumor-bearing nude mice of 7.7% ID/g tissue weight. These results show that the high lipophilicity of the SiFA moiety can be compensated by applying hydrophilic moieties. Using this approach, a tumor-affine SiFA-containing peptide could successfully be used for receptor imaging for the first time in this proof of concept study.

Acid and alkali etching of grit blasted zirconia: Impact on adhesion and osteogenic differentiation of MG63 cells in vitro

There is a need for evaluating zirconia surface modifications and their potential impact on the biological response of osteogenic cells. Grit blasted zirconia discs were either left untreated or underwent acid or alkaline etching. Adhesion and osteogenic differentiation of MG63 cells was determined after one week of culture. The macro-scaled roughness of the grit blasted zirconia discs, independent of the surface treatment, was within a narrow range and only slightly smoother than titanium discs. However, the alkaline- and acid-etching led to an increase of the micro-roughness of the surface. The surface modifications had no effect on cell spreading and did not cause significant change in the expression of differentiation markers. Thus, in this respective setting, morphologic changes observed upon treatment of grit blasted zirconia discs with acid or alkaline do not translate into changes in MG63 cell adhesion or differentiation and are comparable to findings with anodized titanium discs.

Prevalence of asymptomatic and electrically undetectable intracardiac inside-out abrasion in silicon-coated Riata® and Riata® ST implantable cardioverter-defibrillator leads

BACKGROUND: Recently, several cases of symptomatic and/or electrically detectable intracardiac inside-out abrasions in silicon-coated Riata® and Riata® ST leads have been described. However, the prevalence in asymptomatic patients with unremarkable implantable cardioverter defibrillator (ICD) interrogation is unknown. The aim of this study was to determine the prevalence of asymptomatic and electrically undetectable intracardiac inside-out abrasion in silicon-coated Riata® and Riata® ST leads. METHODS: All 52 patients with an active silicone-coated Riata® and Riata® ST lead followed up in our outpatient clinic were scheduled for a premature ICD interrogation and a biplane chest radiograph. When an intracardiac inside-out abrasion was suspected, this finding was confirmed by fluoroscopy. RESULTS: Mean time since implantation was 71±18months. An intracardiac inside-out abrasion was confirmed by fluoroscopy in 6 patients (11.5%). Mean time from lead implantation to detection of intracardiac inside-out abrasion was 79±14months. In all patients with an intracardiac inside-out abrasion, ICD interrogation showed normal and stable electrical parameters. Retrospectively, in 4 of these 6 patients, a coronary angiography performed 25±18months before diagnosis of intracardiac inside-out abrasion already showed the defect. Despite undetected intracardiac inside-out abrasion, 2 of these 4 patients experienced adequate antitachycardia pacing and ICD-shocks. ICD leads were replaced in all 6 patients. CONCLUSIONS: The prevalence of asymptomatic intracardiac inside-out abrasion in silicon-coated Riata® and Riata® ST leads is higher than 10% when assessed by fluoroscopy, and most intracardiac inside-out abrasions are not detectable by ICD interrogation.

PVR recurrence and the timing of silicon oil removal

BACKGROUND: Following vitrectomy for PVR-associated retinal detachment, placement of an encircling band, filling with silicone oil (SO) and successful retinal reattachment, a recurrence of PVR can develop. Retinal redetachment after SO removal is usually due to secondary or residual PVR. We wanted to ascertain whether the anatomical and functional outcomes of surgery in patients with a reattached retina and recurrent PVR can be improved by delaying the removal of SO. PATIENTS AND METHODS: 112 consecutive patients with PVR-associated retinal detachment who had undergone vitrectomy with SO filling, were monitored for at least 6 months after SO removal. Prior to SO removal, the retina posterior to the encircling band had to be completely reattached. Patients who developed PVR after SO filling were divided into two groups according to the duration of SO retention: 12 - 18 months (group 2: n = 48); > 18 months (group 3: n = 21). Individuals without PVR recurrence after SO filling and in whom the SO was consequently removed within 4 - 12 months served as control (group 1: n = 43). Anatomical success, intraocular pressure (IOP) and best-corrected visual acuity (BCVA) served as the primary clinical outcome parameters. RESULTS: Six months after SO removal, the anatomical success rates (86.3 %, 88.8 % and 84.6 %, in groups 1, 2 and 3, respectively; log rank = 0.794) and the BCVAs (p = 0.861) were comparable in the three groups. Mean IOP (p = 0.766), and the frequency of complications such as PVR recurrence (p = 0.936), bullous keratopathy (p = 0.981) and macular pucker (p = 0.943) were likewise similar. Patients in whom SO was retained for more than 18 months had the highest IOPs and required the heaviest dosage with anti-glaucoma drugs. CONCLUSIONS: In patients who develop a recurrence of PVR after vitrectomy and SO filling the surgeon can observe and treat retinal changes for up to 18 months without impairing the anatomical and functional outcomes. The retention of SO for more than 18 months does not improve the anatomical outcome. However, it can impair the functional outcome by precipitating the development of a persisting secondary glaucoma.

Should 3K zoom function be used for detection of pneumothorax in cesium iodide/amorphous silicon flat-panel detector radiographs presented on 1K-matrix soft copies?

The purpose of the study was to evaluate observer performance in the detection of pneumothorax with cesium iodide and amorphous silicon flat-panel detector radiography (CsI/a-Si FDR) presented as 1K and 3K soft-copy images. Forty patients with and 40 patients without pneumothorax diagnosed on previous and subsequent digital storage phosphor radiography (SPR, gold standard) had follow-up chest radiographs with CsI/a-Si FDR. Four observers confirmed or excluded the diagnosis of pneumothorax according to a five-point scale first on the 1K soft-copy image and then with help of 3K zoom function (1K monitor). Receiver operating characteristic (ROC) analysis was performed for each modality (1K and 3K). The area under the curve (AUC) values for each observer were 0.7815, 0.7779, 0.7946 and 0.7066 with 1K-matrix soft copies and 0.8123, 0.7997, 0.8078 and 0.7522 with 3K zoom. Overall detection of pneumothorax was better with 3K zoom. Differences between the two display methods were not statistically significant in 3 of 4 observers (p-values between 0.13 and 0.44; observer 4: p = 0.02). The detection of pneumothorax with 3K zoom is better than with 1K soft copy but not at a statistically significant level. Differences between both display methods may be subtle. Still, our results indicate that 3K zoom should be employed in clinical practice.