In vivo imaging of vascular adhesion protein 1 - preclinical studies with positron emission tomography

The golden standard in nuclear medicine imaging of inflammation is the use of radiolabeled leukocytes. Although their diagnostic accuracy is good, the preparation of the leukocytes is both laborious and potentially hazardous for laboratory personnel. Molecules involved in leukocyte migration could serve as targets for the development of inflammation imaging agents. An excellent target would be a molecule that is absent or expressed at low level in normal tissues, but is induced or up-regulated at the site of inflammation. Vascular adhesion protein-1 (VAP-1) is a very promising target for in vivo imaging, since it is translocated to the endothelial cell surface when inflammation occurs. VAP-1 functions as an endothelial adhesion molecule that participates in leukocyte recruitment to inflamed tissues. Besides being an adhesion molecule, VAP-1 also has enzymatic activity. In this thesis, the targeting of VAP-1 was studied by using Gallium-68 (68Ga) labeled peptides and an Iodine-124 (124I) labeled antibody. The peptides were designed based on molecular modelling and phage display library searches. The new imaging agents were preclinically tested in vitro, as well as in vivo in animal models. The most promising imaging agent appeared to be a peptide belonging to the VAP-1 leukocyte ligand, Siglec-9 peptide. The 68Ga-labeled Siglec-9 peptide was able to detect VAP-1 positive vasculature in rodent models of sterile skin inflammation and melanoma by positron emission tomography. In addition to peptides, the 124I-labeled antibody showed VAP-1 specific binding both in vitro and in vivo. However, the estimated human radiation dose was rather high, and thus further preclinical studies in disease models are needed to clarify the value of this imaging agent. Detection of VAP-1 on endothelium was demonstrated in these studies and this imaging approach could be used in the diagnosis of inflammatory conditions as well as melanoma. These studies provide a proof-of-concept for PET imaging of VAP-1 and further studies are warranted.Siirretty Doriast

"The person I once was has come back to life" : The effectiveness of rehabilitation on the life management and psychosocial well-being of late-deafened adults

Objective The objective of this study was to learn about the psychosocial well-being and life management of Finnish adults with late deafness or hearing loss and to observe the effectiveness of the rehabilitation courses they participated in. Methods For my study I used indicators which were suitable for the evaluation of life management and psychosocial well-being of late-deafened adults. The first part of the study was conducted during 2009 as a questionnaire on three rehabilitation courses in Kopola, a course center of the Finnish Federation of Hard of Hearing. The follow-up study was done at the third period of the courses during 2009 2010. The questionnaire contained both open and structured questions. The questionnaire consisted of five areas concerning life management and psychosocial well-being: sense of coherence (life management), human relations and social support, mood, self-esteem and satisfaction with life. I also asked the participants to reflect on their experiences of group rehabilitation. Results and conclusions The participants consisted of seven women and three men. They were approximately 63 years old and were all retired. Loss of hearing was described to have affected their social life, free time, and in general made their lives more difficult. From the course the participants hoped to gain new skills such as signed speech and lip-reading, uplift their mood, accept their loss of hearing and experience peer support. After the courses they replied that they had more close relations with whom they also were a little more in contact with. More participants were satisfied with e.g. their ability to take care of themselves, their free time, financial situation, family life, mental resources and physical shape. Majority of the participants showed symptoms of depression when the courses started, but at the end of the courses these signs had moderated or disappeared for most of them. The participants felt that during the rehabilitation they had been heard, respected, accepted and been taken care of. The course provided the possibility for confiding, and the discussions gave the participants support and consolidation. In conclusion, the course affected positively on the acclimatization to the hearing loss and the empowerment of the participants. The results of this study can be utilized in disability services, the development of rehabilitation and in the social- and health services of senior citizens.Tavoitteet Tutkimuksen tavoitteena oli saada lisää tietoa aikuisena kuuroutuneiden ja vaikeasti huonokuuloisten henkilöiden psykososiaalisesta hyvinvoinnista ja elämänhallinnasta sekä tarkastella kuuroutuneiden kurssitoiminnan vaikuttavuutta. Menetelmät Tutkimuksessani käytin kuntoutuksen tutkimuksen mittareita, jotka sopivat sovellettaviksi kuuroutuneiden kuntoutuksen arviointiin tarkasteltaessa elämänhallintaa ja psykososiaalista hyvinvointia. Keräsin aineiston kyselylomakkein Kuuloliiton Kopolan kurssikeskuksessa kolmella kuntoutuskurssin aloitusjaksolla 2009 sekä seurantakyselynä saman kurssin kolmannella jaksolla 2009 2010. Kysely sisälsi sekä avoimia että strukturoituja kysymyksiä. Kysely käsitteli viittä elämänhallinnan ja psykososiaalisen hyvinvoinnin aluetta: koherenssintunne (elämänhallinta), ihmissuhteet ja niistä saatu tuki, mieliala, itsetunto sekä tyytyväisyys elämään. Lisäksi kysyin kurssilaisten kokemuksia ryhmäkuntoutuksesta. Tulokset ja johtopäätökset Kyselyn vastaajista naisia oli seitsemän ja miehiä kolme. Vastaajat olivat keskimäärin 63-vuotiaita. Kaikki vastaajat olivat eläkkeellä. Kuuroutumisen kuvattiin vaikuttaneen vastaajien sosiaaliseen elämään, vapaa-aikaan sekä vaikeuttaneen elämää. Kurssilta vastaajat toivoivat uusien taitojen kuten viitotun puheen ja huuliltaluvun oppimista, mielialan kohennusta, kuuroutumisen hyväksymisen oppimista sekä vertaistukea. Kurssien jälkeen vastaajien läheisten ihmisten määrä oli kasvanut ja yhteydenpito tihentynyt hieman. Aiempaa useampi vastaaja oli tyytyväinen mm. kykyynsä huolehtia itsestään, vapaa-aikaansa, taloudelliseen tilanteeseensa, perhe-elämäänsä, henkisiin voimavaroihinsa sekä fyysiseen kuntoonsa. Enemmistöllä vastaajista oli masennukseen viittaavia oireita kurssien alkaessa. Kuntoutuksen aikana lähes jokaisen vastaajan oireet lievenivät tai poistuivat kokonaan. Vastaajat kokivat, että kuntoutuksessa heitä oli kuultu ja arvostettu, heidät oli hyväksytty ja heistä oli pidetty huolta. Kurssi tarjosi mahdollisuuden uskoutumiseen, ja keskustelut antoivat tukea ja vahvistusta. Kurssin voi todeta vaikuttaneen positiivisesti kurssilaisten sopeutumiseen ja voimaantumiseen. Tutkielman tuloksia voidaan hyödyntää vammaispalveluissa, kuntoutuksen kehittämistyössä sekä laajemmin ikääntyneiden sosiaali- ja terveydenhuollossa

The Finnish Five-String Kantele: Sustainably Designed for Musical Joy

Peer reviewe

Translating the concept of peptide labeling with 5-deoxy-5-[F-18] fluororibose into preclinical practice : F-18-labeling of Siglec-9 peptide for PET imaging of inflammation

Peer reviewe

Defects in CD4+ T cell LFA‐1 integrin‐dependent adhesion and proliferation protect Cd47−/− mice from EAE

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141316/1/jlb0493.pd

A Comparative 68Ga-Citrate and 68Ga-Chloride PET/CT Imaging of Staphylococcus aureus Osteomyelitis in the Rat Tibia

There may be some differences in the in vivo behavior of Ga-68-chloride and Ga-68-citrate leading to different accumulation profiles. This study compared Ga-68-citrate and Ga-68-chloride PET/CT imaging under standardized experimental models. Methods. Diffuse Staphylococcus aureus tibial osteomyelitis and uncomplicated bone healing rat models were used (n = 32). Two weeks after surgery, PET/CT imaging was performed on consecutive days using Ga-68-citrate or Ga-68-chloride, and tissue accumulation was confirmed by ex vivo analysis. In addition, peripheral quantitative computed tomography and conventional radiography were performed. Osteomyelitis was verified by microbiological analysis and specimens were also processed for histomorphometry. Results. In PET/CT imaging, the SUVmax of Ga-68-chloride and Ga-68-citrate in the osteomyelitic tibias (3.6 +/- 1.4 and 4.7 +/- 1.5, resp.) were significantly higher (P = 0.0019 and P = 0.0020, resp.) than in the uncomplicated bone healing (2.7 +/- 0.44 and 2.5 +/- 0.49, resp.). In osteomyelitic tibias, the SUVmax of Ga-68-citrate was significantly higher than the uptake of Ga-68-chloride (P = 0.0017). In animals with uncomplicated bone healing, no difference in the SUVmax of Ga-68-chloride or Ga-68-citrate was seen in the operated tibias. Conclusions. This study further corroborates the use of Ga-68-citrate for PET imaging of osteomyelitis

68Ga-DOTA chelate, a novel imaging agent for assessment of myocardial perfusion and infarction detection in a rodent model

BackgroundMagnetic resonance imaging (MRI) with Gadolinium 1,4,7,10-tetraazacyclododecane-N′,N″,N′′′,N″″-tetraacetic acid (Gd-DOTA) enables assessment of myocardial perfusion during first-pass of the contrast agent, while increased retention can signify areas of myocardial infarction (MI). We studied whether Gallium-68-labeled analog, 68Ga-DOTA, can be used to assess myocardial perfusion on positron emission tomography/computed tomography (PET/CT) in rats, comparing it with 11C-acetate.MethodsRats were studied with 11C-acetate and 68Ga-DOTA at 24 hours after permanent ligation of the left coronary artery or sham operation. One-tissue compartmental models were used to estimate myocardial perfusion in normal and infarcted myocardium. After the PET scan, hearts were sectioned for autoradiographic detection of 68Ga-DOTA distribution.Results11C-acetate PET showed perfusion defects and histology showed myocardial necrosis in all animals after coronary ligation. Kinetic modeling of 68Ga-DOTA showed significantly higher k1 values in normal myocardium than in infarcted areas. There was a significant correlation (r = 0.82, P = 0.001) between k1 values obtained with 68Ga-DOTA and 11C-acetate. After 10 minutes of tracer distribution, the 68Ga-DOTA concentration was significantly higher in the infarcted than normal myocardium on PET imaging and autoradiography.ConclusionsOur results indicate that acute MI can be detected as reduced perfusion, as well as increased late retention of 68Ga-DOTA.</p