Design and preclinical evaluation of a novel apelin-based PET radiotracer targeting APJ receptor for molecular imaging of angiogenesis.

APJ has been extensively described in the pathophysiology of angiogenesis and cell proliferation. The prognostic value of APJ overexpression in many diseases is now established. This study aimed to design a PET radiotracer that specifically binds to APJ. Apelin-F13A-NODAGA (AP747) was synthesized and radiolabeled with gallium-68 ([68Ga]Ga-AP747). Radiolabeling purity was excellent (> 95%) and stable up to 2 h. Affinity constant of [67Ga]Ga-AP747 was measured on APJ-overexpressing colon adenocarcinoma cells and was in nanomolar range. Specificity of [68Ga]Ga-AP747 for APJ was evaluated in vitro by autoradiography and in vivo by small animal PET/CT in both colon adenocarcinoma mouse model and Matrigel plug mouse model. Dynamic of [68Ga]Ga-AP747 PET/CT biodistributions was realized on healthy mice and pigs for two hours, and quantification of signal in organs showed a suitable pharmacokinetic profile for PET imaging, largely excreted by urinary route. Matrigel mice and hindlimb ischemic mice were submitted to a 21-day longitudinal follow-up with [68Ga]Ga-AP747 and [68Ga]Ga-RGD2 small animal PET/CT. [68Ga]Ga-AP747 PET signal in Matrigel was significantly more intense than that of [68Ga]Ga-RGD2. Revascularization of the ischemic hind limb was followed by LASER Doppler. In the hindlimb, [68Ga]Ga-AP747 PET signal was more than twice higher than that of [68Ga]Ga-RGD2 on day 7, and significantly superior over the 21-day follow-up. A significant, positive correlation was found between the [68Ga]Ga-AP747 PET signal on day 7 and late hindlimb perfusion on day 21. We developed a new PET radiotracer that specifically binds to APJ, [68Ga]Ga-AP747 that showed more efficient imaging properties than the most clinically advanced tracer of angiogenesis, [68Ga]Ga-RGD2.

In vitro activity of dalbavancin against Gram-positive bacteria isolated from diabetic foot osteomyelitis.

BACKGROUND: Diabetic foot infections (DFIs) represent a serious threat to public health because of their frequency and the severity of their consequences, i.e. osteomyelitis and amputation. The management of diabetic foot osteomyelitis (DFOM) requires prolonged antibiotic therapy. In Western countries, Gram-positive bacteria are the most commonly encountered pathogens. OBJECTIVES: This study evaluated the in vitro activity of dalbavancin, a novel lipoglycopeptide with extended half-life, recently marketed in Europe for acute bacterial skin and skin structure infections, on a panel of Gram-positive bacteria responsible for DFOM. METHODS: Dalbavancin activity was evaluated against a panel of Gram-positive bacterial strains isolated from bone biopsies performed by a trained surgeon among patients with suspected DFOM. MICs were determined using MIC Test Strips (Liofilchem) and confirmed with the EUCAST broth microdilution method. Three other antimicrobial agents (vancomycin, teicoplanin and ceftobiprole) were used as comparators. RESULTS: Dalbavancin showed excellent activity against all Gram-positive bacterial strains tested, including one teicoplanin-resistant Staphylococcus epidermidis isolate. With MIC50 and MIC90 values of 0.047 and 0.094 mg/L, respectively, dalbavancin showed the most potent in vitro activity among antimicrobial agents tested. CONCLUSIONS: With its efficacy, good tolerability and unique pharmacokinetic properties, dalbavancin appears to be a promising treatment for DFOM involving Gram-positive bacteria.

Pharmaceutical interviews to overcome digestive artefacts on [99m Tc]Tc-tetrofosmin myocardial perfusion scintigraphy.

WHAT IS KNOWN AND OBJECTIVES: Poor image quality was randomly seen in [99m Tc]Tc-tetrofosmin myocardial perfusion scintigraphic imaging. The interference hampered or even precluded medical interpretation. Our objective was to identify the cause of the random interferences. METHODS: Out of 40 patients planned for [99m Tc]Tc-tetrofosmin MPS, 36 presented normal tracer uptake and 4 exhibited subdiaphragmatic artefacts. Pharmaceutical interviews (P.I.) were set up to formally identify aetiologies of subdiaphragmatic uptake of [99m Tc]Tc-tetrofosmin. Patients were questioned about their diet and current drug treatments. RESULTS AND DISCUSSION: P.I. led to identification of dipyridamole as the cause of the artefacts. The systematic ingestion of a solid 25-gram high-fat snack bar and a glass of fresh water was introduced immediately after the injection of dipyridamole in 12 other patients undergoing [99m Tc]Tc-tetrofosmin MPS. None of the 12 patients presented subdiaphragmatic artefacts. WHAT IS NEW AND CONCLUSION: P.I. identified the cause of poor scintigraphic images to allow improved diagnoses.