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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
Diserahkan: 9 Oktober 2008 / Diterima: 1 Disember
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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