Synthesis and Characterization of Gadolinium Diethylenetriamine Pentaacetate-Folate

Fauzia, Ratna Putri; Mutalib, Abdul; Soedjanaatmadja, R. Ukun M.S.; Bahti, Husein H.; Anggraeni, Anni; Gunawan, Adang Hardi; Pujiastuti, H.; Hidayati, Y.

doi:10.1016/j.proche.2015.12.128

Cited by 10 publications

(8 citation statements)

References 4 publications

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“…With recent advances in technology, the MRI has gradually become a very powerful diagnostic tool by providing high quality tissue images . The ability to distinguish different types of tissues by making use of various acquisition protocols and the innate high soft-tissue contrast enable MRI to offer excellent anatomic details. , It has also been described as one of the most important techniques of modern medicine because it shows high spatial resolution and is capable of a tomographic 3D presentation and monitoring of dynamic physiological changes . Particularly, the brain, nerves, spinal cord, ligaments, tendons, and muscles can be viewed much more clearly in these images when compared to those of computer tomography (CT), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and X-rays, leading to MRI application in, for example, imaging of a broad variety of joint injuries. ,, Additionally, increased radiation risks associated with X-ray and radionuclide-based imaging techniques have been reported, including increased risks of cancer that cannot be associated with MRI .…”

Section: Introductionmentioning

confidence: 99%

The Transition from Metal-Based to Metal-Free Contrast Agents for T₁ Magnetic Resonance Imaging Enhancement

et al. 2019

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Magnetic resonance imaging (MRI) has received significant attention as the noninvasive diagnostic technique for complex diseases. Image-guided therapeutic strategy for diseases such as cancer has also been at the front line of biomedical research, thanks to the innovative MRI, enhanced by the prior delivery of contrast agents (CAs) into patients' bodies through injection. These CAs have contributed a great deal to the clinical utility of MRI but have been based on metal-containing compounds such as gadolinium, manganese, and iron oxide. Some of these CAs have led to cytotoxicities such as the incurable Nephrogenic Systemic Fibrosis (NSF), resulting in their removal from the market. On the other hand, CAs based on organic nitroxide radicals, by virtue of their structural composition, are metal free and without the aforementioned drawbacks. They also have improved biocompatibility, ease of functionalization, and long blood circulation times, and have been proven to offer tissue contrast enhancement with longitudinal relaxivities comparable with those for the metal-containing CAs. Thus, this Review highlights the recent progress in metal-based CAs and their shortcomings. In addition, the remarkable goals achieved by the organic nitroxide radical CAs in the enhancement of MR images have also been discussed extensively. The focal point of this Review is to emphasize or demonstrate the crucial need for transition into the use of organic nitroxide radicalsmetal-free CAsas against the metal-containing CAs, with the aim of achieving safer application of MRI for early disease diagnosis and image-guided therapy.

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Section: Introductionmentioning

confidence: 99%

The Transition from Metal-Based to Metal-Free Contrast Agents for T₁ Magnetic Resonance Imaging Enhancement

et al. 2019

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“…We succeeded in conjugating the rHSA from P. pastoris SMD1168 with Gd-DTPA to form Gd-DTPA-rHSA with high purity. This serves as a contrast agent and is required in high purity since free DTPA molecules and Gd 3+ ions are dangerous and toxic (Fauzia et al, 2015;Gallo et al, 2020;Rinck, 2018;Schmiedl et al, 1987;Wallnöfer et al, 2020). The results of this study indicate that the deficient protease host P. pastoris SMD1168 can be used to express rHSA, and conjugation with Gd-DTPA produced a complex with high purity.…”

Section: Discussionmentioning

confidence: 64%

Expression of human serum albumin in Pichia pastoris protease-deficient host and conjugation with gadolinium-diethylenetriamine pentaacetate for application as a contrast agent

Gaffar¹,

Anggraeni²,

Novianti³

et al. 2021

J Appl Pharm Sci

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Human serum albumin (HSA) is a plasma protein with a molecular weight of 66.5 kDa, which is most widely used in the pharmaceutical and clinical fields. One application of HSA in a drug delivery system is to increase the relaxation time on magnetic resonance imaging. The combination of contrast agent, gadolinium-diethylenetriamine pentaacetate (Gd-DTPA), with HSA can produce better imaging. This study aims to express the recombinant HSA (rHSA) in the Pichia pastoris protease-deficient host, SMD1168, purification using chromatographic techniques and conjugation with Gd-DTPA. Optimization of rHSA expression by P. pastoris was done by varying the methanol inducer, 0.75%, 1.0%, 1.25%, and 1.5%, as well as characterization by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Furthermore, the rHSA was purified using gel filtration, characterization by Size Exclusion Chromatography-High Performance Liquid Chromatography (SEC-HPLC), and conjugation with Gd-DTPA. The rHSA (~66.5 kDa) was characterized from broth medium of P. pastoris SMD1168. The optimum conditions for rHSA expression were 1.5% methanol at 48 hours incubation, which resulted in 0.44 g/l of rHSA. The rHSA with 81.84% purity was obtained by gel filtration, and conjugation with Gd-DTPA produced high-purity Gd-DTPA-rHSA, demonstrated by a single peak (rt = 10.493 minutes). The proteasedeficient P. pastoris was successfully used to express intact rHSA and the rHSA was successfully conjugated to Gd-DTPA with high purity.

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“…2016;Gries at al. 2009) yang akan tertarget pada sel kanker yang positif reseptor folat telah berhasil disintesis menjadi Gadolinium Dietilentriaminpentaasetat-Folat (Gd-DTPA-Folat) dalam kurun waktu 2 tahun terakhir dan menghasilkan rendemen yang cukup baik dari reaksi antara ion gadolinium dengan ligan DTPA-Folat, yang disiapkan melalui prekursornya yaitu EDA-Folat melalui metode langsung dan tidak langsung (Fauzia et al 2015;Fauzia dkk. 2017) seperti 67 Gadefroksamin-Folat (Wang et al 1996) dan 111 In-DTPA-Folat (Wang et al 1997).…”

Section: Pendahuluanunclassified

Aplikasi Desain Eksperimen Plackett-Burman dan Response Surface Methodology Box-Behnken pada Produksi Senyawa Pengontras Magnetic Resonance Imaging Gadolinium Dietilentriaminpentaasetat-Folat

et al. 2017

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Abstrak: Desain Plackett-Burman digunakan untuk menyeleksi variabel yang memiliki pengaruh utama dalam produksi Gadolinium Dietilentriaminpentaasetat-Folat (Gd-DTPA-Folat) sebagai senyawa pengontras Magnetic Resonance Imaging (MRI). Tujuh variabel seperti rasio mol Gadolinium (Gd) dan ligan Dietilentriaminpentaasetat-Folat (DTPA-Folat), suhu, laju pengadukan, pH, waktu reaksi dan volume pelarut diseleksi dalam proses produksi. Faktor dummy yang tidak memiliki pengaruh secara kimia ditambahkan juga dalam eksperimen. Dari ketujuh variabel, rasio mol Gd dan DTPA-Folat, laju pengadukan dan volume pelarut memiliki pengaruh yang positif terhadap persentase hasil rendemen Gd-DTPA-Folat. Tahapan selanjutnya adalah mengetahui interaksi antara faktor-faktor yang berpengaruh positif dalam eksperimen dan menghasilkan respon optimum untuk keseluruhan variabel menggunakan Response Surface Methodology Box-Behnken. Pendekatan statistik dalam studi untuk eksperimen desain menggunakan Software Design Expert 9.0.6.2. Kesimpulan dalam hasil penelitian adalah bahwa kondisi reaksi optimum dalam produksi Gd-DTPA-Folat, yaitu rasio mol Gd dan DTPA-Folat 10:1, laju pengadukan 500 RPM dan volume pelarut sebanyak 20 mL (untuk 2,5 x 10 -4 mmol ligan). Prediksi hasil rendemen Gd-DTPA-Folat pada kondisi optimum adalah 87,3296%. Abstract: Plackett-Burman design was used to efficiently select variabel which have a main effect in production of Gadolinium Diethylenetriaminepentaacetate-Folate (Gd-DTPA-Folate) as a novel Magnetic Resonance Imaging (MRI) contrast agents. Seven variabels which are mole ratio of Gadolinium (Gd) toDiethylenetriaminepentaacetate-Folate (DTPA-Folate) ligand, temperature, stirring rate, pH, reaction time, and volume of solvent were screened in the whole process. Dummy factors which have no chemical meaning at all was added to the experiments. Out of the seven variables, mole ratio of Gd to DTPA-Folate, stirring rate and volume of solvent were found to affected positively to the yiled percentage of Gd-DTPA-Folate. The next step was investigated the interaction between factors which affected positively in the experiments and to obtain optimum responses for these whole process variables using Response Surface Methodology Box-Behnken. The statistical approach in this study for design experiments were using Software Design Expert 9.0.6.2. From the result, we concluded that the optimum reaction condition in production Gd-DTPA-Folate was using 10:1 as a mole ratio of Gd and DTPA-Folate, 500 RPM as a stirring rate and volume of solvent is 20 mL (for 2,5x10 -4 mmol ligand). The predicted yield of Gd-DTPA-Folate using the optimum condition was 87,3296%.

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Synthesis and Characterization of Gadolinium Diethylenetriamine Pentaacetate-Folate

Cited by 10 publications

References 4 publications

The Transition from Metal-Based to Metal-Free Contrast Agents for T₁ Magnetic Resonance Imaging Enhancement

The Transition from Metal-Based to Metal-Free Contrast Agents for T₁ Magnetic Resonance Imaging Enhancement

Expression of human serum albumin in Pichia pastoris protease-deficient host and conjugation with gadolinium-diethylenetriamine pentaacetate for application as a contrast agent

Aplikasi Desain Eksperimen Plackett-Burman dan Response Surface Methodology Box-Behnken pada Produksi Senyawa Pengontras Magnetic Resonance Imaging Gadolinium Dietilentriaminpentaasetat-Folat

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Synthesis and Characterization of Gadolinium Diethylenetriamine Pentaacetate-Folate

Cited by 10 publications

References 4 publications

The Transition from Metal-Based to Metal-Free Contrast Agents for T1 Magnetic Resonance Imaging Enhancement

The Transition from Metal-Based to Metal-Free Contrast Agents for T1 Magnetic Resonance Imaging Enhancement

Expression of human serum albumin in Pichia pastoris protease-deficient host and conjugation with gadolinium-diethylenetriamine pentaacetate for application as a contrast agent

Aplikasi Desain Eksperimen Plackett-Burman dan Response Surface Methodology Box-Behnken pada Produksi Senyawa Pengontras Magnetic Resonance Imaging Gadolinium Dietilentriaminpentaasetat-Folat

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The Transition from Metal-Based to Metal-Free Contrast Agents for T₁ Magnetic Resonance Imaging Enhancement

The Transition from Metal-Based to Metal-Free Contrast Agents for T₁ Magnetic Resonance Imaging Enhancement