Benzodiazepin (Diazepam) ve cyclopyrrolone (Zopiclone) grubu formasötiklerinin I-131 ile işaretlenmesi
Küçük Resim Yok
Tarih
1998
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Kısa ömürlü radyoizotoplarla işaretli radyofarmasötiklerin Nükleer Tıp'taki kullanımlarının günden güne artması bu radyoizotopların elde edilmesi ve radyofarmasötiklerin hazırlanması ile ilgili diğer disiplinlerin de önemini arttırmıştır. Kuşkusuz Nükleer Tıp'ın gelişmesi bu konu ile ilgili disiplinler olan Radyofarmasi ve Radyokimya'nın da gelişmesine bağlıdır. Bu çalışmada bu düşünceden hareketle yeni bir radyofarmasötikler grubu olarak benzodiazepin grubundan 1.4 benzodiazepin ailesinin bir üyesi olan ve geniş çapta uyku ilacı olarak kullanılan diazepam, cyclopyrrolone ailesinin yeni bir türevi olan zopiclone (4-metil -1- piperazin karboksilik asit, 6-(5-kloro-2-piridin)-6-7-dihidro 7-okso-5 H- pirrol [3.4-b] pirazin-5 ester) isimli farmasötikler I-131 ile işaretlenmiş ve radyofarmasötik potansiyelleri belirlenmeye çalışılmıştır. Diazepam'ın I-131 ile işaretlenmesi ile ilgili olarak CAT ve iodogen yöntemleri denenmiş ve her iki yöntem için de optimum işaretlenme koşulları belirlenmiştir. CAT yöntemi için en uygun koşullar;diazepam miktarı 1 mg, CAT miktarı 11.2 mg, reaksiyon süresi 30 dakika, reaksiyon sıcaklığı oda sıcaklığı'dır. Bu yönteme göre elde edilen 13 l IDZ verimi %72.5'dir. İodogen yöntemine göre ise uygun koşullar; diazepam miktarı 1-5 mg, iodogen miktarı 1 mg, reaksiyon süresi 15-20 dakika ve reaksiyon sıcaklığı oda sıcaklığı olarak belirlenmiştir. Asidik şartlarda yapılan işaretlemede % 84 işaretleme verimi elde edilirken ticari ampul çözeltisi içindeki nötral şartlarda % 64 işaretlenme verimi elde edilmiştir. Bu şartlarda elde edilen 131IDZ'in spesifik aktivitesi 0.28 Ci/mmol mertebesindedir. Zopiclone'nun 1-131 ile işaretlenmesinde bu yöntemler başarılı olmamış ve erime noktasında halojen yer değiştirme yöntemi iyi sonuç vermiştir. Bu yöntemde en uygun işaretleme koşullan; zopiclone miktarı 1 mg, reaksiyon sıcaklığı 70-80 °C, reaksiyon süresi 1 saat'dir. Bu koşullarda 131IZP verimi % 96.8 dir. Spesifik aktivite 0.15 Ci/mmol mertebesindedir. Her iki radyofarmasötiğin lipofilitesini tesbit için n-oktanol/su oranlan tayin edilmiş ve 131IDZ için 1.9, 131IZP için 1.6 bulunmuştur. Her iki işaretli bileşiğinde radyofarmasötik potansiyelleri belirlemek için in vivo denemeler yapılmıştır. Sıçanlar üzerinde yapılan biyolojik dağılım çalışmaları 131IDZ'ın böbrek, karaciğer, akciğer, beyin gibi organlarda 131IZP'nun ise dalak, kas, akciğer, karaciğer, yağ dokusu, beyin gibi organlarda en çok birikim gösterdiklerini göstermiştir. Gama kamera ile tavşanlar üzerinde yapılan sintigrafik çalışma sonuçlan da sıçanlar ile yapılan biyolojik dağılım çalışması sonuçlarını desteklemektedir. Anahtar sözcükler: Diazepam, Zopiclone, iodogen yöntemi, 1-131 ile işaretleme, halojen yer değiştirme yöntemi, CAT yöntemi
Since usage of radioisotopically labeled radiopharmaceuticals increase day by day, importance of the other disciplines that is related with this area have increased. Certainly developing of the Nuclear Medicine dependes on the Radiopharmacy and Radiochemistry that are the most related disciplines with this scientific area. In this study, diazepam is a derivative of the 1.4 benzodiazepine family that the most widely used drugs as anticonvulsant agents and zopiclone (4-methyl-l-piperazine carboxylic acid, 6-(5-chloro~2- pyridyl)-6,7-dihydro-7-oxo-5 H- pyrrolo-[3.4-b]-pyrazin 5-yl ester) is a new derivative of the cyclopyrrolone family have been labeled with I- 131, as new radiopharmaceuticals and their radiopharmaceutical potentials have been determined. CAT and iodogen methods have been tried for labeling of diazepam with 1-131 and optimum labeling conditions have been determined for both methods. The optimum conditions for CATmethods; diazepam amount is 1 mg, CAT amount is 11.2 mg, reaction time is 30 minutes, reaction temperature is room temperature. 131IDZ yield is 72.5 % according to this method. The specific activity of labeled compound was 0.28 Ci/mmol level. The optimum conditions for iodogen method; diazepam amount is 1-5 mg, iodogen amount is 1 mg, reaction time is 15-20 minutes and reaction temperature is room temperature. Eighty-four percent and 64 % labeling yields were obtained for acidic and neutral media respectively. Specific activity of labeled compound was 0.28 Ci/mmol level. Labeling of zopiclone with 1-131 couldn't be succeeded by these methods. For this reason, halogen exchange at melting point method was tried and gave good result. Optimum labeling conditions according to this method; zopiclone amount is 1 mg, reaction temperature is 70-80 °C, reaction time is one hour. Labeling yield is 96.8 %. The specific activity of labeled compound was 0. 15 Ci/mmol level. The ratios of n-octanol/water were determined for both radiopharmaceuticals 1.9 for 131IDZ, 1.6 for 131IZP were found. In vivo experiments have been done to determine radiopharmaceutical potentials of both labeled compounds. Biodistribution studies on rats showed that 13 lTDZ has accumulated in kidneys, liver, lungs, brain tissues while 131IZP has accumulated in spleen, muscle, lungs, liver, fat tissus and brain tissues. Scintigraphic results taken with gamma camera on rabbits agree with biodistribution results of rats. Key words: Diazepam, Zopiclone, iodogen method, labelled with 1-131, halogen exchange method, CAT method.
Since usage of radioisotopically labeled radiopharmaceuticals increase day by day, importance of the other disciplines that is related with this area have increased. Certainly developing of the Nuclear Medicine dependes on the Radiopharmacy and Radiochemistry that are the most related disciplines with this scientific area. In this study, diazepam is a derivative of the 1.4 benzodiazepine family that the most widely used drugs as anticonvulsant agents and zopiclone (4-methyl-l-piperazine carboxylic acid, 6-(5-chloro~2- pyridyl)-6,7-dihydro-7-oxo-5 H- pyrrolo-[3.4-b]-pyrazin 5-yl ester) is a new derivative of the cyclopyrrolone family have been labeled with I- 131, as new radiopharmaceuticals and their radiopharmaceutical potentials have been determined. CAT and iodogen methods have been tried for labeling of diazepam with 1-131 and optimum labeling conditions have been determined for both methods. The optimum conditions for CATmethods; diazepam amount is 1 mg, CAT amount is 11.2 mg, reaction time is 30 minutes, reaction temperature is room temperature. 131IDZ yield is 72.5 % according to this method. The specific activity of labeled compound was 0.28 Ci/mmol level. The optimum conditions for iodogen method; diazepam amount is 1-5 mg, iodogen amount is 1 mg, reaction time is 15-20 minutes and reaction temperature is room temperature. Eighty-four percent and 64 % labeling yields were obtained for acidic and neutral media respectively. Specific activity of labeled compound was 0.28 Ci/mmol level. Labeling of zopiclone with 1-131 couldn't be succeeded by these methods. For this reason, halogen exchange at melting point method was tried and gave good result. Optimum labeling conditions according to this method; zopiclone amount is 1 mg, reaction temperature is 70-80 °C, reaction time is one hour. Labeling yield is 96.8 %. The specific activity of labeled compound was 0. 15 Ci/mmol level. The ratios of n-octanol/water were determined for both radiopharmaceuticals 1.9 for 131IDZ, 1.6 for 131IZP were found. In vivo experiments have been done to determine radiopharmaceutical potentials of both labeled compounds. Biodistribution studies on rats showed that 13 lTDZ has accumulated in kidneys, liver, lungs, brain tissues while 131IZP has accumulated in spleen, muscle, lungs, liver, fat tissus and brain tissues. Scintigraphic results taken with gamma camera on rabbits agree with biodistribution results of rats. Key words: Diazepam, Zopiclone, iodogen method, labelled with 1-131, halogen exchange method, CAT method.
Açıklama
Anahtar Kelimeler
Nükleer Mühendislik, Nuclear Engineering, Benzodiazepinler, Benzodiazepines, Cyclopyrrolone, Cyclopyrrolone, Farmasötikler, Pharmaceuticals