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Clearance profile of radioactive gold nanoparticle (198Au) conjugates-poliamidoamin generation 4-nimotuzumab ; potential radio-pharmaceutical theranostic agent Nurhatidjah Awaliyah Halid; Abdul Mutalib; Anung Pujiyanto; Adang Hardi Gunawan
Pharmaciana Vol 7, No 2 (2017): Pharmaciana
Publisher : Universitas Ahmad Dahlan

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (581.999 KB) | DOI: 10.12928/pharmaciana.v7i2.6725

Abstract

Theranostic agents are agents that combine diagnostic and therapeutic capabilities into a single agent. The presence of conjugated cancer which is therapeutic agents such as nimotuzumab monoclonal antibodies with radioactive gold nanoparticles stabilized with Polyamidoamine Generation 4 (PAMAM G4) dendrimer can actively interact with specific cancer cells. Radioactive gold (198Au) as a radiation transmitter β (961 keV) capable for killing cancer cells and (412 keV) γ rays that give a golden image in the body, thus acting as a theranostic agent. The purpose of this study was to obtain confident results of conjugate safety by observing the constituent clearance of 198AuNP-PAMAM G4-Nimotuzumab. The result of the conjugate clearance will be the reference for the metabolic state as a new, stable and complete radiofarmaka upon reaching the desired target. This study began with the synthesis of the conjugate of 198AuNp-PAMAM G4-nimotuzumab and then tested the clirens and analyzed the results of urine and mouse feces that had been injected with conjugate. Total clearance was obtained about 47.38% of the 198AuNP-PAMAM G4-Nimotuzumab conjugates that have been excreted through urine (18.26%) and stool (29.11%.). Urine and feces were analyzed with SDS-PAGE giving the spot above the 150 kDa band and showing the conjugate molecular weight. FTIR analysis of urine and feces by showing aldehyde functional groups (C = O), alcoholic groups (O-H), amine groups (C-N), and amine groups (N-H) indicating the presence of AuNP-PAMAM G4-Nimotuzumab conjugates in urine and mouse feces. The results of urine and fecal excretion of the conjugate are still conjugate-shaped supported by SDS PAGE analysis, UV-Vis spectrophotometer absorption analysis and functional group analysis with FTIR that has been conducted.
Profil Distribusi dan Klirens Pengkontras CT SCAN AuNP-PAMAM G4- NIMOTUZUMAB disimulasikan menggunakan Senyawa 198AuNP-PAMAM G4-NIMOTUZUMAB Adang H G; Anung Pujiyanto; Abdul Mutalib; Rista A S; Indrarini L; Rien L; Iyus M Y; Herlan S; Sutriyo C
Jurnal Kimia Terapan Indonesia Vol 18, No 01 (2016)
Publisher : Research Center for Chemistry - LIPI

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (235.035 KB) | DOI: 10.14203/jkti.v18i01.38

Abstract

Riset nanopartikel emas sebagai senyawa pengkontras CT-Scan telahdimulai sejak 3 tahun lalu di Indonesia. Riset interaksi antibodi monoklonal,khususnya nimotuzumab, dengan reseptor EGFR/HER1 dimulai sejak lima tahun lalu dan telah dimanfaatkan untuk penyiapan senyawa pengkontras MRI (Magnetic Resonance Imaging) spesifik target melalui pelabelan konjugat dendrimer-nimotuzumab dengan radionuklida. Sintesis senyawa AuNP-PAMAM G4-Nimotuzumab untuk diagnosis dan terapi pada kanker paru-paru telah berhasil dilakukan di PTRR dan hasil karakterisasinya dengan menggunakan beberapa metode seperti KCKT (Kromatografi Cair Kinerja Tinggi), SDS (Sodium Dodecyl Sulphate) page elektroforesa dan TEM (Transmission Electron Microscopy) menunjukkan bahwa senyawa yang terbentuk adalah sebagai AuNP-PAMAM G4-Nimotuzumab. Pada penelitian ini telah dilakukan uji pre klinis dari senyawa pengkontras AuNPPAMAM G4-nimotuzumab meliputi uji distribusi dan klirens dengan disimulasikan menggunakan senyawa radioaktiv 198AuNP-PAMAM G4- nimotuzumab. Hasil uji distribusi senyawa 198AuNP-PAMAM G4- nimotuzumab menunjukkan penimbunan pada beberapa organ seperti ginjal, hati dan limpa, sedangkan dari hasil uji klirens diperoleh waktu paruh biologis senyawa tersebut adalah 11.77 hari. Hasil pemeriksaan terhadap urin dengan menggunakan kolom PD-10 (Sephadex G25) menunjukkan bahwa ~ 85 % yang dikeluarkan lewat urin masih berbentuk AuNP-PAMAM G4- Nimotuzumab. Hasil pencitraan dengan alat autoradiography menunjukkan bahwa sampai dengan 48 jam setelah penyuntikan, akumulasi radioaktivitas yang terdeteksi masih terdapat pada hati.Â