Joustavan vaatimustenhallinnan soveltaminen emissioidenhallintakonseptin luomiseen

Verkostopuolustuksen periaatteen toteutuminen suorituskykyjen ja osaamisen täysimääräisestä hyödyntämisestä on pitkälti riippuvainen toimivasta emissionhallinnasta. Emissionhallinnan konseptilla ohjataan sekä suorituskykyjen suunnittelua ja rakentamista että toiminnallista emissionhallintaa sotilasoperaatioissa. Konseptin puuttuessa verkostopuolustuksen edellyttämän yhteensopivuuden saavuttaminen on vaikeaa, jopa mahdotonta. Artikkelissa esitellään malli suorituskykyjen vaatimustenhallinnan dynamiikan – joustavuuden– aikaansaamiseksi sekä sovelletaan tätä mallia emissionhallinnan kokonaiskonseptin luomiseksi

68Ga-Citrate Positron Emission Tomography of Healthy Men: Whole-Body Biodistribution Kinetics and Radiation Dose Estimates

68Ga-citrate has one of the simplest chemical structures of all 68Ga-radiopharmaceuticals, and its clinical use is justified by the proven medical applications using its isotope-labeled compound 67Ga-citrate. To support broader application of 68Ga-citrate in medical diagnosis, further research is needed to gain clinical data from healthy volunteers. In this work, we studied the biodistribution of 68Ga-citrate and subsequent radiation exposure from it in healthy males. Methods: 68Ga-citrate was prepared with an acetone-based radiolabeling procedure compliant with Good Manufacturing Practices. Six healthy males (age 41 ± 12 years, mean ± SD) underwent sequential whole-body PET/CT scans after an injection of 204 ± 8 MBq of 68Ga-citrate. Serial arterialized venous blood samples were collected during PET imaging and the radioactivity concentration was measured with a gamma counter. Urinary voids were collected and measured. The Medical Internal Radiation Dose (MIRD) bladder-voiding model with a 3.5 hour voiding interval was used. A model using a 70 kg adult male and MIRD schema was used to estimate absorbed doses in target organs and effective doses. Calculations were performed using OLINDA/EXM 2.0 software. Results: Radioactivity clearance from the blood was slow, and relatively high radioactivity concentrations were observed over the whole of the 3 hour measuring period. Although radioactivity excretion via urine was rather slow (biological half-time, 69 ± 24 hours), the highest decay-corrected concentrations in urinary bladder contents were measured at 90 and 180 minute time points. Moderate concentrations were also seen in kidneys, liver, and spleen. The source organs showing the largest residence times were muscle, liver, lung, and heart contents. The heart wall received the highest absorbed dose of 0.077 ± 0.008 mSv/MBq. The mean effective dose (ICRP 103) was 0.021 ± 0.001 mSv/MBq. Conclusion: PET imaging with 68Ga-citrate is associated with modest radiation exposure. A 200 MBq injection of 68Ga-citrate results in an effective radiation dose of 4.2 mSv, which is in the same range as other 68Ga-labeled tracers. This suggests the feasibility of clinical studies using 68Ga-citrate imaging in humans and the possibility of performing multiple scans in the same subjects across the course of a year.</p

First-in-Human Study of 68 Ga-DOTA-Siglec-9, PET Ligand Targeting Vascular Adhesion Protein 1

Sialic acid-binding immunoglubulin-like lectin 9 (Siglec-9) is a ligand of vascular adhesion protein 1 (VAP-1). A gallium 68-labeled peptide of Siglec-9, 68Ga-DOTA-Siglec-9, holds promise as a novel PET tracer for imaging of inflammation. This first-in-human study investigated the safety, tolerability, biodistribution, and radiation dosimetry of this radiopharmaceutical. Methods: Six healthy males underwent dynamic whole-body PET/CT. Serial venous blood samples were drawn from 1-240 min after intravenous injection of 162 ± 4 MBq of 68Ga-DOTA-Siglec-9. In addition to gamma counting, the plasma samples were analyzed by high-performance liquid chromatography to detect intact tracer and radioactive metabolites. Radiation doses were calculated using the OLINDA/EXM 2.2 software. In addition, a patient with early rheumatoid arthritis was studied with both 68Ga-DOTA-Siglec-9 and 18F-FDG PET/CT to determine the ability of the new tracer to detect arthritis. Results: 68Ga-DOTA-Siglec-9 was well tolerated by all subjects. 68Ga-DOTA-Siglec-9 was rapidly cleared from blood circulation and several radioactive metabolites were detected. The organs with the highest absorbed doses were the urinary bladder wall (0.38 mSv/MBq) and kidneys (0.054 mSv/MBq). The mean effective dose was 0.022 mSv/MBq (range 0.020-0.024 mSv/MBq). Most importantly, however, 68Ga-DOTA-Siglec-9 was able to detect arthritis comparable to 18F-FDG. Conclusion: Intravenous injection of 68Ga-DOTA-Siglec-9 was safe and biodistribution is favorable for testing of the tracer in larger group of patients with rheumatoid arthritis planned in the next phase of clinical trials. The effective radiation dose of 68Ga-DOTA-Siglec-9 was within the same range as those of other 68Ga-labeled tracers. Injection of 150 MBq of 68Ga-DOTA-Siglec-9 would expose a subject to 3.3 mSv. These findings support the possible repeated clinical use of 68Ga-DOTA-Siglec-9, e.g., in trials aiming to elucidate the treatment efficacy of novel drug candidates

Effect of celiprolol therapy arterial dilatation in experimental hypertension.

Syventävä työ ei kirjastoss

Effect of celiprolol therapy arterial dilatation in experimental hypertension.

Syventävä työ ei kirjastoss