SINTESA DAN PENANDAAN SENYAWA 5’-O-(4,4’-DIMETOKSITRITIL)- 2,3-ANHIDROTIMIDIN UNTUK PREPARASI RADIOFARMAKA [ 18 F]FLT

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ABSTRAK

SINTESA DAN PENANDAAN SENYAWA 5’-O-(4-4’-DIMETOKSITRITIL)-2,3-ANHIDROTIMIDIN UNTUK PREPARASI RADIOFARMAKA [18F]FLT

Telah diketahui bahwasenyawa 3'-deoksi-3'- [18F] Florotimidin  atau [18F]FLT adalah radiofarmaka turunan timidin yangdigunakan untuk deteksi kanker berdasar pada metabolisme DNA. Telah dilakukan kegiatan penelitiantentang sintesa dan penandaan senyawa prekursor 5'-O-(4,4'-dimetoksitritil)-2,3' anhidrotimidin untukpreparasi radiofarmaka [18F]FLT. Sintesa dan penandaan prekursor dilakukan sesuai metoda literatur  dantelah diperoleh produk berupa kristal hablur  84,37 mg (yield  32,4 %) dengan kemurnian kimia lebih dari95 % (HPLC). Karakterisasi dilakukan dengan mengamati hasil pengujian liquid chromatography-massspectrometry LC/MS dan  penentuan1H-NMR,  menunjukkan bahwa produk 5'-O-(4,4'-dimetoksitritil)-2,3' anhidrotimidin dari hasil sintesa tidak berbeda jauh dengan hasil yang diperoleh dari literatur. Penandaansenyawa prekursor dilakukan melalui reaksi florinasi nukleofilik menggunakan18Florida pada suhu 1600Cselama 15 menit dengan katalisator kriptofix 2.2.2, dilanjutkan dengan hidrolisa menggunakan HCl padasuhu 1000C selama 10 menit, kemudian dinetralkan dengan NaOH. Pemurnian [18F]FLT terhadap pengotordilakukan dengan kartrid tunggal Alumina-N sebagai pengganti pemurnian dengan HPLC. Pengujiankualitas [18F]FLT yang dilakukan meliputi kejernihan larutan, pH dan kemurnian radiokimia.

Hasilpengujian terhadap empat kali percobaan penandaan menunjukkan bahwa telah  diperoleh senyawa [18F]FLTberupa  larutan jernih tak berwarna dengan pH antara 6,0 – 7,5, kemurnian radiokimia 97,93 ± 1,48 %dengan perolehan 8,18 ± 1,54 % (tanpa koreksi waktu peluruhan) dan waktu proses penandaan selama 73 ± 4menit.

Kata kunci : Sintesa - Radiofarmaka - [18F]FLT - Deteksi- Kanker

ABSTRACT

SYNTHESIS AND LABELING 5'-O-(4-4'-DIMETOXYTRITYL) -2,3-ANHIDROTHYMIDINE  FORPREPARATION OF RADIOPHARMACEUTICAL [18F]FLT.

It is has been known that the compoundof 3'-deoxy-3'-[18F] Fluorothymidine or [18F] FLT is a thymidine derivative radiopharmaceutical used forcancer detection based on DNA metabolism. Synthesis and labeling of 5'-O-(4,4 '-dimetoxytrityl) -2,3'anhidrothymidine precursor for preparation of the radiopharmaceutical [18F]FLT was carried out. Theprecursor was synthesized in similar manner and procedure literature and it have been obtained a crystallineproduct with total yield of 32,4 %. The chemical purity of the product which determined by HPLC wasfound to be more than 95%. Characterization of the product was done by observing the results of the LC /MS and1H-NMR test, the resulted data were found to be very closed to those reported in the literature.Labeling of the precursor was done by nucleophilic fluorination reactions using18Fluoride at 1600C for 15minutes with kryptofix 2.2.2 catalyst followed hydrolysis using HCl at 1000C for 10 minutes and thenneutralized with NaOH. Purification [18F]FLT was performed by single cartridge Alumina-N as a substituteHPLC methods. The results have been obtained a label compound [18F]FLT with high purity as a bulk forpreparation of the radiopharmaceutical [18F]FLT. The label compound of [18F]FLT undergone a quality testwhich included a clarity, pH and a radiochemical purity. The results of quality control on four batches of[18F]FLT showed that these products were colorless clear solution with pH between 6.0-7.5, andradiochemical purity 97.93 ± 1,48% and showed that the label compounds have been obtained [18F]FLTfree particles form a clear solution with a pH between 6,0 - 7,5, radiochemical purity of 97.93 ± 1,48 %,radiochemical yields 8.18 ± 1.54% (decay uncorrected ) and processing time 73 ± 4 minutes.

Keywords: Synthesis - Radiofarmaka - [18F]FLT - Detection-CancerSintesa dan Penandaan Senyawa 5’-O-(4,4’-Dimetoksitritil)- 2,3-Anhidrotimidin untuk Preparasi Radiofarmaka [1