Development of radiosynthesis methods for 18F-labelled radiopharmaceuticals : General considerations and production of a dopamine transporter radioligand

Positron emission tomography (PET) is a molecular imaging technique that utilises radiopharmaceuticals (radiotracers) labelled with a positron-emitting radionuclide, such as fluorine-18 (18F). Development of a new radiotracer requires an appropriate radiosynthesis method: the most common of which with 18F is nucleophilic substitution with [18F]fluoride ion. The success of the labelling reaction is dependent on various factors such as the reactivity of [18F]fluoride, the structure of the target compound in addition to the chosen solvent. The overall radiosynthesis procedure must be optimised in terms of radiochemical yield and quality of the final product. Therefore, both quantitative and qualitative radioanalytical methods are essential in developing radiosynthesis methods. Furthermore, biological properties of the tracer candidate need to be evaluated by various pre-clinical studies in animal models. In this work, the feasibility of various nucleophilic 18F-fluorination strategies were studied and a labelling method for a novel radiotracer, N-3-[18F]fluoropropyl-2beta-carbomethoxy-3beta-4-fluorophenyl)nortropane ([18F]beta-CFT-FP), was optimised. The effect of solvent was studied by labelling a series of model compounds, 4-(R1-methyl)benzyl R2-benzoates. 18F-Fluorination reactions were carried out both in polar aprotic and protic solvents (tertiary alcohols). Assessment of the 18F-fluorinated products was studied by mass spectrometry (MS) in addition to conventional radiochromatographic methods, using radiosynthesis of 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[18F]MPPF) as a model reaction. Labelling of [18F]beta-CFT-FP was studied using two 18F-fluoroalkylation reagents, [18F]fluoropropyl bromide and [18F]fluoropropyl tosylate, as well as by direct 18F-fluorination of sulfonate ester precursor. Subsequently, the suitability of [18F]beta-CFT-FP for imaging dopamine transporter (DAT) was evaluated by determining its biodistribution in rats. The results showed that protic solvents can be useful co-solvents in aliphatic 18F-fluorinations, especially in the labelling of sulfonate esters. Aromatic 18F-fluorination was not promoted in tert-alcohols. Sensitivity of the ion trap MS was sufficient for the qualitative analysis of the 18F-labelled products; p-[18F]MPPF was identified from the isolated product fraction with a mass-to-charge (m/z) ratio of 435 (i.e. protonated molecule [M+H]+). [18F]beta-CFT-FP was produced most efficiently via [18F]fluoropropyl tosylate, leading to sufficient radiochemical yield and specific radioactivity for PET studies. The ex vivo studies in rats showed fast kinetics as well as the specific uptake of [18F]beta-CFT-FP to the DAT rich brain regions. Thus, it was concluded that [18F]beta-CFT-FP has potential as a radiotracer for imaging DAT by PET.Positroniemissiotomografia (PET) on kuvantamismenetelmä, jossa hyödynnetään lyhytikäisillä positronisäteilijöillä, kuten fluori-18:lla, leimattuja radioaktiivisia yhdisteitä, ns. radiolääkeaineita. PET:n ja 18F-leimattujen radiolääkeaineiden tärkeitä sovellutuskohteita on mm. neurologiassa, esimerkkinä dopamiinin kuljetusproteiinien (DAT) diagnostinen kuvantaminen: DAT:n toiminnan on osoitettu muuttuneen monissa neurologisissa ja psykiatrisissa sairauksissa kuten Parkinsonin taudissa. Uusien, spesifisten radiolääkeaineiden tuottaminen edellyttää sopivan radioleimausmenetelmän kehittämistä ja leimattujen yhdisteiden biologisten ominaisuuksien määrittämistä eläinmalleissa. Tyypillinen leimausreaktio 18F:lla perustuu nukleofiiliseen substituutioon [18F]fluoridilla. Leimausreaktion onnistumiseen voidaan vaikuttaa monilla tekijöillä, joita ovat mm. [18F]fluoridin reaktiivisuus, kohdemolekyylin rakenne sekä valittu liuotin. Tavoitteena on tuottaa puhdas lopputuote mahdollisimman hyvällä radioaktiivisella saannolla ja riittävän korkealla spesifisellä radioaktiivisuudella, näin ollen myös asianmukaiset analyysimenetelmät ovat ensisijaisen tärkeitä valmistusmenetelmän kehityksessä. Tämän väitöskirjatyön tarkoituksena oli tutkia erilaisia nukleofiilisiä 18F-fluorausmenetelmiä ja optimoida valmistusmenetelmä uudelle DAT -merkkiaineelle, N-3-[18F]fluoripropyyli)-2beta-karbometoksi-3beta-4-fluorifenyyli)nortropaanille ([18F]beta-CFT-FP). Liuottimen ja lähtöaineen rakenteen vaikutusta leimausreaktion onnistumiseen tutkittiin radioleimaamalla erilaisia malliyhdisteitä, 4-(R1-metyyli)bentsyyli R2-bentsoaatteja, sekä yleisesti käytetyissä aproottisissa että uusissa proottisissa liuottimissa. Tulokset osoittivat, että tertiääriset alkoholit soveltuvat alifaattisten yhdisteiden, erityisesti sulfonaattiesterien leimaukseen, mutta aromaattisissa 18F-fluorausreaktioissa ne eivät toimineet. Serotoniinireseptori 5HT1A -ligandin, 4-[18F]fluori-N-[2-[1-(2-metoksifenyyli)-1-piperatsinyyli]etyyli-N-2-pyridinyyli-bentsamidi (p-[18F]MPPF), valmistuksessa käytettiin leimautuneiden tuotteiden analysointiin perinteisten kromatografisten menetelmien rinnalla massaspektrometriaa (MS). Ioniloukku-MS:n todettiin olevan riittävän herkkä menetelmä leimatun lopputuotteen tunnistamiseen reaktioseoksesta. [18F]beta-CFT-FP:n radioleimausta tutkittiin käyttäen kahta, 18F-fluoroalkylointiin pohjautuvaa menetelmää sekä suoraa yksivaiheista leimausmenetelmää, joista [18F]fluoripropyyli tosylaatti leimausreagenssina osoittautui toimivimmaksi: optimoitu leimausmenetelmä mahdollistaa [18F]beta-CFT-FP:n valmistamisen potilastutkimuksiin. Lisäksi [18F]beta-CFT-FP -merkkiaineen biologisia ominaisuuksia tutkittiin rotilla ex vivo. Tulokset osoittivat, että yhdiste kulkeutuu nopeasti ja spesifisesti aivoalueille, joissa DAT-proteiineja on runsaasti. Johtopäätöksenä todetaan, että [18F]beta-CFT-FP soveltuu DAT:n kuvantamiseen PET:lla

Vitamin C for preventing and treating tetanus

BACKGROUND: Tetanus is a severe disease that can be prevented by vaccination. In developing countries vaccination coverage is not always high. Cases still occur also in developed countries, particularly in elderly people owing to their reduced immuno protection. There are about 1 million tetanus cases per year globally. In animal studies, vitamin C has protected against various infections and bacterial toxins. In a study with rats, vitamin C protected against the purified tetanus toxin. OBJECTIVES: To assess the prophylactic and therapeutic effect of vitamin C on tetanus. SEARCH METHODS: In May 2013 we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations ); and Ovid EMBASE for this third update. SELECTION CRITERIA: Controlled trials of vitamin C as a prevention or treatment for tetanus, whether or not these were placebo controlled, in any language, published or unpublished. Two review authors independently made inclusion decisions. DATA COLLECTION AND ANALYSIS: Both review authors independently extracted data from trial reports and assessed methodological quality. Since one of the cells in a 2 × 2 table had no events, we calculated the odds ratio (OR) and its 95% confidence interval (CI) for case fatality rate by using the Peto-method. Another of the 2 × 2 tables had no empty cells and the inverse-variance method was used to calculate its risk ratio (RR) estimate and 95% CI. We also used the Fisher's exact test to calculate the exact 95% CI for the OR of the 2 × 2 table with the empty cell. MAIN RESULTS: One single trial was eligible for inclusion. This non-randomised, unblinded, controlled trial undertaken in Bangladesh involved 117 tetanus patients. Vitamin C at a dosage of 1 g/day was administered intravenously alongside conventional treatment. At recruitment, the participants were stratified into two age groups and the results were reported by age. There was a significant difference in the vitamin C effect between the two age groups (P = 0.01). In the tetanus patients aged 1 to 12 years (n = 62), vitamin C treatment was associated with a 100% reduction in case fatality rate (95% CI from -100% to -94%). In patients aged 13 to 30 years (n = 55), vitamin C treatment was associated with a 45% reduction in case fatality rate (95% CI from -69% to -5%). AUTHORS' CONCLUSIONS: A single, non-randomised, poorly reported trial of vitamin C as a treatment for tetanus suggests a considerable reduction in mortality. However, concerns about trial quality mean that this result must be interpreted with caution and vitamin C cannot be recommended as a treatment for tetanus on the basis of this evidence. New trials should be carried out to examine the effect of vitamin C on tetanus treatment.Peer reviewe

Rivaroksabaanin kustannusvaikuttavuus varfariiniin verrattuna ei-läppäperäisen eteisvärinän aiheuttaman aivohalvauksen estossa : järjestelmällinen kirjallisuuskatsaus

Atrial fibrillation is the most common sustained cardiac arythmia. It has been estimated that there will be 14 to 17 million atrial fibrillation patients in Europe by the year 2030. In Finland, there are over 50 000 atrial fibrillation patients. The prevalence of atrial fibrillation increases by age. In addition to age, people who have hearth failure, high blood pressure, coronary artery disease, valvular hearth disease, diabetes mellitus, chronic kidney disease or who suffer from obesity have increased prevalence. Atrial fibrillation is usually not a life threatening condition. However, people who suffer from atrial fibrillation have a greater risk of the stroke compared with people who have normal sinus rhythm. Warfarin has been the standard treatment for preventing the stroke in atrial fibrillation patients. However, there are many inconveniences in warfarin therapy such as food and drug interactions and frequent laboratory visits. Therefore, new oral anticoagulants have been introduced to prevent the stroke in non-valvular atrial fibrillation. These new drugs apixaban, dabigatran, edoxaban and rivaroxaban are more expensive than warfarin. Many people suffer from atrial fibrillation and the number of atrial fibrillation patients is increasing. Due to the expected increase in the number of atrial fibrillation patients in future the costs of the new drugs have led to a concern for their impact on the health care budget. The knowledge of the cost-effectiveness of the new anticoagulants is important for decision making. In this Master's thesis, the cost-effectiveness of rivaroxaban was compared with warfarin for stroke prevention in non-valvular atrial fibrillation. Systematic literature review was used as the study method and 363 studies were screened and 23 of them filled the inclusion criteria. One was a previously published systematic review and 22 were cost-utility studies. All of the cost-utility studies had used decision analytic modelling. The studies were conducted in 13 different countries. In the cost-utility studies included in this systematic review there was a great variability in the cost-effectiveness of rivaroxaban compared with warfarin. Rivaroxaban was cost-effective in more than half of the studies, for example in Belgium, Italy, Norway and Singapore. However, in China, Thailand and Slovenia the cost-effectiveness could not be established. Contradictory cost-effectiveness results were obtained in studies conducted in Germany, Canada and USA. The incremental cost-effectiveness ratio varied from 2580 € to 174915 € per quality adjusted life years (QALY) gained with warfarin over all the 22 cost-utility studies. In studies conducted in Europe the incremental cost effectiveness ratio varied from 4188 € 139163 €/QALY gained. In studies where rivaroxaban, apixaban, dabigatran and warfarin were compared together using an indirect comparison or a network meta-analysis it seemed that rivaroxaban was not the optimal treatment. The most common adverse effect of anticoagulation treatment is bleeding. This complication was included in all the cost-utility studies. However, there was only some uniformity of the bleeding events reported. In most cost-utility studies the acute care cost of intracranial hemorrhages was reported and in many studies, also the long term costs. The cost-utility studies included in this systematic review were quite heterogeneous. Because they were done in different countries their health care settings, treatment options and costs were different. There were also differences in cost-effective models. Modell structure, settings, data and assumptions were different. Due to the heterogeneous nature of the studies, no unambiguous answer could be reached to the question concerning the cost-effectiveness of rivaroxaban compared with warfarin. The quality assessment of the cost-utility studies revealed that some quality criteria were not met. Transferability of the results from one country to the other seemed to be poor. The strength of this master's thesis is the comprehensive literature search concerning the cost-effectiveness of rivaroxaban compared with warfarin. Also, the reporting of methods and results are transparent. There are also limitations in this study. One person was conducting the literature search, data extraction and quality assessment. This might have increased the risk for subjective interpretations and errors.Eteisvärinä on yleisin pitkäkestoinen rytmihäiriö. Vuoteen 2030 mennessä Euroopassa arvioidaan olevan 14-17 miljoonaa eteisvärinäpotilasta. Suomessa eteisvärinäpotilaita on yli 50000. Eteisvärinän esiintyvyys lisääntyy iän mukana. Iän lisäksi altistavia tekijöitä ovat sydämen vajaatoiminta, verenpainetauti, sepelvaltimotauti, läppäperäinen sydänsairaus, liikalihavuus, diabetes ja krooninen munuaissairaus. Eteisvärinä ei välttämättä ole henkeä uhkaava, mutta eteisvärinää sairastavien riski saada sydänperäisestä emboliasta aiheutuva aivohalvaus on merkittävästi kohonnut verrattuna niihin, jotka eivät sairasta eteisvärinää. Aivohalvausten eston standardihoito on pitkään ollut varfariini. Varfariinihoidolla on kuitenkin monia ongelmia kuten interaktiot lääkkeiden ja ruoan kanssa ja vähintään kerran kuussa tehtävät laboratoriomittaukset. Viimeisen kymmenen vuoden aikana markkinoille on tullut uusia antikoagulantteja eteisvärinän aiheuttaman aivohalvauksen estoon. Nämä uudet lääkkeet apiksabaani, dabigatraani, edoksabaani ja rivaroksabaani ovat merkittävästi kalliimpia kuin varfariini. Koska eteisvärinää sairastavia on paljon ja potilaiden määrän uskotaan kasvavan eliniän pidentyessä, on uusien antikoagulanttien käyttöönotto herättänyt huolta terveydenhuollon rahoituksen riittävyydestä. Tietoa uusien antikoagulanttien kustannusvaikuttavuudesta tarvitaan päätöksenteon avuksi. Tässä pro gradu -tutkielmassa arvioitiin yhden uuden suun kautta otettavan antikoagulantin, rivaroksabaanin, kustannusvaikuttavuutta varfariiniin verrattuna ei-läppäperäisen eteisvärinän aiheuttaman aivohalvauksen estossa. Tutkimusmenetelmänä käytettiin järjestelmällistä kirjallisuuskatsausta. Kirjallisuuskatsauksen tietokantahauissa löydettiin 363 viitettä, joista mukaanottokriteerit täyttyivät 23 artikkelissa. Näistä yksi oli aikaisempi järjestelmällinen kirjallisuuskatsaus ja loput 22 olivat kustannusutiliteettitutkimuksia. Kaikki kustannusutiliteettitutkimukset olivat päätösanalyyttisia mallinnuksia. Tutkimukset oli tehty kolmessatoista eri maassa. Rivaroksabaanin kustannusvaikuttavuus varfariiniin verrattuna osoittautui vaihtelevaksi pro gradu -työn järjestelmällisen kirjallisuuskatsauksen tutkimuksissa. Se oli kustannusvaikuttava yli puolessa tutkimuksissa, muun muassa Belgiassa, Italiassa, Norjassa ja Singaporessa. Sen sijaan Kiinassa, Thaimaassa ja Sloveniassa rivaroksabaani ei osoittautunut kustannusvaikuttavaksi. Ristiriitaisia kustannusvaikuttavuustuloksia saatiin Saksassa Kanadassa ja Yhdysvalloissa. Rivaroksabaanin inkrementaalinen kustannusvaikuttavuussuhde varfariiniin verrattuna vaihteli 2580-174915 € saatua laatupainotettua elinvuotta (QALY) kohden kaikissa tutkimuksissa. Eurooppalaisissa tutkimuksissa inkrementaalinen kustannusvaikuttavuussuhde oli pienimmillään 4188 € ja suurimmillaan139163 € saatua laatupainotettua elinvuotta kohti. Niissä tutkimuksissa, joissa rivaroksabaanin, apiksabaanin, dabigatraanin ja varfariinin kustannusvaikuttavuutta arvioitiin toisiinsa verrattuna käyttämällä epäsuoraa vertailua tai verkostometa-analyysiä, havaittiin, että rivaroksabaani oli harvoin optimaalinen hoitovaihtoehto. Verenvuodot ovat antikoagulaatiohoidon yleisimpiä haittoja. Ne oli otettu mukaan kaikissa kustannusutiliteettianalyyseissä, mutta ilmoitetuissa vuototapahtumissa oli vaihtelua. Yleisimmin tutkimuksissa oli otettu huomioon kallon sisäisen verenvuodon akuuttihoitokustannukset ja usein myös pitkäaikaishoitokustannukset. Järjestelmällisen kirjallisuuskatsauksen kustannusutiliteettitutkimuksissa oli vaihtelua. Koska ne oli tehty eri maissa, niiden terveydenhuoltojärjestelmät, hoitokäytännöt ja kustannukset vaihtelivat. Vaihtelua oli myös mallien rakenteessa, tutkimusasetelmissa, käytetyissä tiedoissa ja oletuksissa. Tutkimusten heterogeenisyyden vuoksi yksiselitteistä vastausta rivaroksabaanin kustannusvaikuttavuudelle ei saatu. Tutkimusten laadussa havaittiin olevan jonkin verran puutteita ja tulosten siirrettävyys maasta toiseen näytti heikolta. Tämän pro gradu -tutkielman vahvuutena oli kattava aineiston kerääminen rivaroksabaanin kustannusvaikuttavuudesta varfariiniin verrattuna sekä menetelmien ja tulosten läpinäkyvä raportointi. Rajoituksena tässä työssä oli, että yksi henkilö etsi julkaisut, poimi tiedot ja arvioi laadun. Tämä menettelytapa on saattanut altistaa työn virheille ja subjektiivisille tulkinnoille

Analysis of Frankia populations in three soils devoid of actinorhizal plants

Frankia populations were analyzed in three soils devoid of actinorhizal plants but containing monocultures of birch (Betula pendula Roth), pine (Pinus sylvestris L.) or spruce (Picea abies (L.) Karsten). Bioassays using seedlings of Alnus incana as capture plants resulted in nodulation capacities of 3160±7, 2267±13, and 2747±6 nodulation units g−1 of these soils, respectively. Comparative sequence analysis of an actinomycetes-specific insertion in domain III of the 23S rRNA allowed a grouping of isolates obtained from nodules of the capture plants into three distinct groups of the Alnus host infection group. This separation was confirmed by the analysis of genomic fingerprints of the isolates generated by rep-PCR fingerprinting with the BOX primer. Genomic fingerprints also demonstrated that all isolates differed from each other. The isolates accounted for a significant proportion of the Frankia population in root nodules of the capture plants as shown by in situ hybridization with specific probes. However, only those Frankia strains isolated from soil of the birch stand via Alnus seemed to represent the total Frankia population in root nodules. Nodules induced after inoculation with soil from the pine or spruce stand also contained Frankia populations which were not isolated during this study and which could not be identified by in situ hybridization. Depending upon whether the soil originated from a birch, pine or spruce stand, different Frankia populations were found in the nodules of the capture plants. Because a nested PCR on nucleic acids extracted from these different soils did not indicate differences in the diversity of the total Frankia populations, it was concluded that Frankia populations in nodules of the capture plants represent the fraction of physiologically active, infecting frankiae in the soils rather than the total Frankia populatio

Assessment of labelled products with different radioanalytical methods: study on 18F-fluorination reaction of 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[18F]MPPF)

Peer reviewe

Fungemia and other Fungal Infections Associated with Use of Saccharomyces boulardii Probiotic Supplements

Because of widespread use of probiotics, their safety must be guaranteed. We assessed use of Saccharomyces boulardii probiotic yeast from medical records for patients who had Saccharomyces fungemia or other clinical Saccharomyces culture findings. We evaluated all Saccharomyces sp. findings at 5 university hospitals in Finland during 2009-2018. We found 46 patients who had Saccharomyces fungemia; at least 20 (43%) were using S. boulardii probiotic. Compared with a control group that had bacteremia or candidemia, the odds ratio for use of an S. boulardii probiotic was 14 (95% CI 4-44). Of 1,153 nonblood culture findings, the history for 125 patients was checked; at least 24 (19%) were using the probiotic (odds ratio 10, 95% CI 3-32). This study adds to published fungemia cases linked to use of S. boulardii probiotic and sheds light on the scale of nonblood Saccharomyces culture findings that are also linked to use of this probiotic.Peer reviewe

Improved synthesis of [18F] fallypride and characterization of a Huntington’s disease mouse model, zQ175DN KI, using longitudinal PET imaging of D2/D3 receptors

Dopamine receptors are involved in pathophysiology of neuropsychiatric diseases, including Huntington’s disease (HD). PET imaging of dopamine D2 receptors (D2R) in HD patients has demonstrated 40% decrease in D2R binding in striatum, and D2R could be a reliable quantitative target to monitor disease progression. A D2/3R antagonist, [18F] fallypride, is a high-affinity radioligand that has been clinically used to study receptor density and occupancy in neuropsychiatric disorders. Here we report an improved synthesis method for [18F]fallypride. In addition, high molar activity of the ligand has allowed us to apply PET imaging to characterize D2/D3 receptor density in striatum of the recently developed zQ175DN knock-in (KI) mouse model of HD.Peer reviewe

Fungemia and Other Fungal Infections Associated with Use of Saccharomyces boulardii Probiotic Supplements

Because of widespread use of probiotics, their safety must be guaranteed. We assessed use of Saccharomyces boulardii probiotic yeast from medical records for patients who had Saccharomyces fungemia or other clinical Saccharomyces culture findings. We evaluated all Saccharomyces sp. findings at 5 university hospitals in Finland during 2009–2018. We found 46 patients who had Saccharomyces fungemia; at least 20 (43%) were using S. boulardii probiotic. Compared with a control group that had bacteremia or candidemia, the odds ratio for use of an S. boulardii probiotic was 14 (95% CI 4–44). Of 1,153 nonblood culture findings, the history for 125 patients was checked; at least 24 (19%) were using the probiotic (odds ratio 10, 95% CI 3–32). This study adds to published fungemia cases linked to use of S. boulardii probiotic and sheds light on the scale of nonblood Saccharomyces culture findings that are also linked to use of this probiotic.</p

Comparison of Clinically Relevant Oncolytic Virus Platforms for Enhancing T Cell Therapy of Solid Tumors

Despite some promising results, the majority of patients do not benefit from T cell therapies, as tumors prevent T cells from entering the tumor, shut down their activity, or downregulate key antigens. Due to their nature and mechanism of action, oncolytic viruses have features that can help overcome many of the barriers currently facing T cell therapies of solid tumors. This study aims to understand how four different oncolytic viruses (adenovirus, vaccinia virus, herpes simplex virus, and reovirus) perform in that task. For that purpose, an immunocompetent in vivo tumor model featuring adoptive tumor-infiltrating lymphocyte (TIL) therapy was used. Tumor growth control (p < 0.001) and survival analyses suggest that adenovirus was most effective in enabling T cell therapy. The complete response rate was 62% for TILs + adenovirus versus 17.5% for TILs + PBS. Of note, TIL biodistribution did not explain efficacy differences between viruses. Instead, immunostimulatory shifts in the tumor microenvironment mirrored efficacy results. Overall, the use of oncolytic viruses can improve the utility of T cell therapies, and additional virus engineering by arming with transgenes can provide further antitumor effects. This phenomenon was seen when an unarmed oncolytic adenovirus was compared to Ad5/3-E2F-d24-hTNFa-IRES-hIL2 (TILT-123). A clinical trial is ongoing, where patients receiving TIL treatment also receive TILT-123 (ClinicalTrials.gov: NCT04217473).</p

Customer relationship management in universities of applied sciences

Artikkelin tavoitteena on herättää keskustelua ammattikorkeakoulujen työelämäyhteyksien asiakkuudenhallinnasta. Korkeakoulutuksen rakennemuutos haastaa ammattikorkeakoulut kilpailemaan toistensa kanssa sekä tavoittelemaan lisäarvoa asiakkailleen niin opetuksessa, tutkimus- ja kehittämistoiminnassa kuin alueellisessa kehittämisessäkin. Artikkeli on syntynyt Mikkelin ammattikorkeakoulun hallinnoiman Aikuiskoulutuksen alueellisen kehittämishankkeen (AIKE) puitteissa. Siinä havaittiin, ettei ammattikorkeakouluissa juurikaan ole käytössä toimivia asiakasrekistereitä ja ettei hajallaan olevia yritysyhteistyötietoja pystytä tehokkaasti hyödyntämään. Yritystoiminnassa asiakkuudenhallinta on koko liiketoiminnan perusta. Asiakkaat tunnetaan, asiakassuhteita vaalitaan ja asiakkaita palkitaan eri tavoin. Tässä suhteessa ammattikorkeakouluilla olisi paljon opittavaa yrityksistä. Asiakkuudenhallinta tulee nähdä ammattikorkeakouluissa aitona kiinnostuksena asiakkaan tarpeista ja toiveista ja pyrkimyksenä toteuttaa niitä käytettävissä olevin keinoin. Tyytyväisten asiakkaiden kautta ammattikorkeakoulu saavuttaa olemassaolonsa oikeutuksen ja toimintaedellytykset. Asiakkuudenhallinta on avainasemassa myös tavoiteltaessa parempaa euromääräistä tulosta ja kannattavaa palveluliiketoimintaa Asiakkuudenhallinnan ottaminen käyttöön ammattikorkeakouluissa edellyttää asenteiden ja toimintatapojen muutosta. Muutos on välttämätön, jotta pystytään vastaamaan ammattikorkeakouluihin kohdistuviin kasvaviin pedagogisiin sekä työelämäyhteistyön ja alueellisen vaikuttavuuden tavoitteisiin.The aim of the article is to provoke discussion about customer relationship management (CRM) in universities of applied sciences concerning enterprises and other organisations. The structural change of higher education institutions, which is leading them to new fusions, makes the universities of applied sciences to compete with each other and seek for better value in education, research and development as well as work for regional development. The article was written within the project ”Developing Regional Adult Education” (AIKE) administered by Mikkeli University of Applied Sciences. In the project it appeared that there are almost no customer registers in universities of applied sciences and that the existing scattered contact information can not be used effectively In enterprises customer relation management is the basis of business operations. Customers are well-known, customer relationships are fostered and customers are awarded with various benefits. In universities of applied sciences there is much to learn from enterprises. In universities of applied sciences customer relationship management should be seen as sincere interest in customer’s needs and expectations and attempt to meet them as well as possible. Through satisfied customers universities of applied sciences gain their legitimacy and operational conditions. Understanding customer relationship management is a key factor also in looking for revenue and profitable service business. Adopting customer relation management in universities of applied sciences presumes a new attitude towards customers and new ways of doing things. In our opinion this process is inevitable if we want to meet the pedagogical challenges and the need of increasing efficiency in co-operation and regional development