Sains Malaysiana 38(4)(2009): 601–607

 

 

Tc99m-Sestamibi: Pembangunan Kit Radiofarmaseutikal untuk Pemetaan Jantung

(Tc99m-Sestamibi: Development of Radiopharmaceutical  Kit For Heart Imaging)

 

W.K. Wan Hamirul Bahrin, M.H. Zulkifli, T. Yahaya, A. Karuppaiya & A. Rasyieda

Bahagian Teknologi Perubatan, Agensi Nuklear Malaysia (Nuklear Malaysia)

Bangi, 43000 Kajang, Selangor, D.E., Malaysia

 

M.A. Mohd Cairul Iqbal* & H. Rosnani

Fakulti Farmasi, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abd. Aziz, 50300 Kuala Lumpur, Malaysia

 

Received: 9 October 2008 / Accepted: 1 December 2008

 

ABSTRAK

Kajian untuk membangunkan dan membandingkan kit radiofarmaseutikal pemetaan jantung sestamibi Nuklear Malaysia (kit NM) dengan kit komersil dilaporkan. Tiga kelompok kit segera liofil B1, B2 and B3 dihasilkan secara pengeringan sejuk beku. Bagi tujuan perbandingan, kit komersil terdiri dari sestamibi Cardiolite, Polatom, ChiMIBI dan tetrofosmin Myoview. Ujian kawalan mutu yang dijalankan ialah ujian mikrobiologi, radiokimia dan kajian secara in vivo haiwan makmal. Ujian mikrobiologi mengesahkan kit NM adalah steril dan bebas pirogen. Ujian ketulenan radiokimia menggunakan kaedah kromatografi turus lapisan nipis segera (ITLC) dan kromatografi cecair berprestasi tinggi (HPLC) adalah melebihi 90% dan kekal stabil sehingga minggu ke-52. Kajian secara in vivo dilakukan ke atas tikus Sprague-Dawley pada selang masa 5, 30, 60, 120 and 1440 minit selepas suntikan dos. Peratus dos suntikan per gram jantung bagi Tc99m-B1 ialah 4.722±0.343%, 3.752±0.438%, 4.564±0.664%, 4.180±1.293% dan 1.090±0.230% pada selang masa 5, 30, 60, 120 dan 1440 minit masing-masing. Ini diikuti oleh Tc99m-B2 iaitu 3.852±0.406%, 3.628±0.425%, 3.366±0.316%, 4.324±1.044% dan 1.038±0.144%; Tc99m-B3 iaitu 5.404±0.351%, 4.818±0.579%, 6.015±0.774%, 5.028±1.353% dan 1.623±0.692%. Analisis statistik Independent T Test mendapati kesemua kit agen pemetaan jantung adalah signifikan bagi jantung berbanding ujian kawalan (P<0.05). Ini membuktikan penyerapan jantung adalah spesifik. Manakala analisis ke atas kit NM, mendapati nilai peratus dos suntikan per gram jantung berada pada nilai kit komersil. Penyingkiran Tc99m-sestamibi NM oleh darah, hati, ginjal dan usus kecil adalah cepat dan efisien. Penyebaran Tc99m-sestamibi NM dengan nisbah jantung terhadap paru-paru dan jantung terhadap hati menunjukkan potensi kit ini sesuai digunakan sebagai agen pemetaan jantung.

 

Kata kunci: kajian in vivo haiwan makmal; ketulenan radiokimia; radiofarmaseutikal; Tc99m-sestamibi

 

ABSTRACT

 

A development and comparison study of the Nuclear Malaysia’s Tc99m-sestamibi heart imaging agents (NM kits) and the commercial products is reported. Three batches of kits labelled as B1, B2 and B3 were produced by freeze drying technique. The commercial products such as sestamibi Cardiolite, Polatom, ChiMIBI and tetrofosmin Myoview were used in this study. The quality control testing which included microbiology testing, radiochemical and animal biodistribution study were conducted accordingly. The NM sestamibi kits passed the sterility and pirogen test. The Radiochemical Purity testing (RCP) was assessed by the Instant Thin Layer Chromatography (ITLC) and High-Performance Liquid Chromatography (HPLC) methods after the reconstitution of the Tc99m-sestamibi. The RCP results were above 90% and the kits were stable for 52 weeks. The animal biodistribution studies were carried out on Sprague-Dawley rats at 5, 30, 60, 120 and 1440 minutes post injection time intervals. The percentage injected dose per gram organ in heart for Tc99m-B1 were 4.722±0.343%, 3.752±0.438%, 4.564±0.664%, 4.180±1.293% and 1.090±0.230% at 5, 30, 60, 120 and 1440 minutes respectively. This is followed by the Tc99m-B2; 3.852±0.406%, 3.268±0.425%, 3.366±0.316%, 4.324±1.044% and 1.038±0.144%, Tc99m-B3; 5.404±0.351%, 4.818±0.579%, 6.015±0.774%, 5.028±1.353% and 1.623±0.692% at the same time intervals. Independent T Test showed that heart uptake was significant as compared to the control (p<0.05). The biodistribution study also showed that the radiopharmaceuticals localized selectively in the myocardium of rats. The NM sestamibi kits were comparable to the commercial products. Blood, lung, kidney and intestines washout were found to be fast and efficient. The biodistribution and analysis of heart-to-lung and heart-to-liver uptake ratios showed that NM sestamibi kits has a potential and could be used as heart imaging agents.

 

Keywords: Animal biodistribution study; radiopharmaceuticals; radiochemical purity; Tc99m-sestamibi

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*Corresponding author; email: mciamin@medic.ukm.my

 

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