Nimotuzumab is an anti group of anti-epidermal growth factor receptor the EGF protein receptor, such as colorectal, brain, pancrea cervical and breast cancer. In order to obtain a of the above-mentioned cancers, nimotuzumab and gamma-emitter 177 Lu. This report discuss vivo tests, which included cytotoxicity, clearance, imaging and biodistribution tests. The cytotoxicity test of (lung carcinoma) was found unradiolabeled nimotuzumab. The on normal rats showed that the residue the urine. The biodistribution and image tests showed that 177 Lu-DOTA-nimotuzumab there organs, such as the kidney, liver and bone post injection of 177 Lu-DOTA nearly the same as or slightly lower compared to other radiolabeled monoclonal antibodies, precautions still ha tested on cancer patients.
Radioiodine is an effective and low-risk therapy modality in well-differentiated thyroid cancer patients post near-total thyroidectomy. Extra thyroidal tumors such as breast cancer are known to be able to uptake radioiodine. The aim of this study was to analyze the uptake, efflux and cytotoxicity of radioiodine for two molecular types of breast cancer cell lines. Two types of breast cancer cell lines were used in this study, MCF-7 (luminal A type) and SKBR3 (HER2 type). The HaCaT cell line was used as normal cells. Iodine-125 (I-125) was used to measured radioiodine uptake and efflux. Clonogenic assay was used to assess cytotoxicity of iodine-131 (I-131) based on the tested cell reproductive ability. The radioiodine uptake in SKBR3 cells was found to be higher than that of MCF-7 and HaCaT cells at p<0.05. The reproductive ability of MCF-7 cells are lower than SKBR3 cells at p<0.05. Both breast cancer cells have less reproduction ability than HaCaT cells at p<0.05. Both types of breast cancer cells present the ability to uptake radioiodine and show a high sensitivity to radioiodine exposure. Normal cells also demonstrate an ability to uptake radioiodine. However, they have a better tolerance to the amount of I-131 exposure. These findings could potentially lead to the use if I-131 for ablative therapy in breast cancer, similiar to its use in the treatment of thyroid cancer.
AIM: This study aims to investigate the effect of ATP, EGF and combination of those two to the Natrium Iodide Symporter (NIS) expression in MCF7, SKBR3 and HaCaT cell lines. METHODS: MCF7, SKBR3 and HaCaT cell lines were treated with ATP, EGF and combination of those two for 6, 12 and 24 hours. The expression of NIS mRNA was measured through quantitative-reverse transcription-polymerase chain reaction (qRT-PCR). The NIS protein expression was confirmed by immunocytofluorescence. RESULTS: NIS mRNA was expressed in SKBR3 and HaCaT cell lines but not in MCF7. The levels of NIS mRNA expression, after treatment by epidermal growth factor (EGF), adenosine Tri-Phosphate (ATP) or the combination of both for 6 and 12 hours were not significantly different from those of untreated cells. However, the treatment by a combination of ATP and EGF for 24 hours increases the level of NIS mRNA expression by 1.6 fold higher than that of the untreated cells (1.6241 ± 0.3, p < 0.05) and protein NIS expression increase significantly by the treatment than untreated cells (P < 0.05). CONCLUSION: The level of NIS expression varies among the different subtypes of breast cancer cell lines. MCF7 cell line is representing the luminal A subtype of breast cancer does not express NIS. Only SKBR3 cell line express NIS and this subtype might be suitable to receive radioiodine therapy as those cells expressing NIS. A combination treatment of EGF and ATP increases the expression of NIS mRNA and protein at the membrane in SKBR3 cells.
The aim of this study was to determine the role of antithyroglobulin antibody (ATA) serum as a marker of successful I-131 ablation therapy in differentiated thyroid cancer (DTC) patients with low serum thyroglobulin (Tg). A retrospective study was conducted on 60 patients (10 males and 50 females). All patients underwent posttotal thyroidectomy and received 2.96 to 3 GBq I-131 ablation. Subjects were divided into two groups with succesful and unsuccessful I-131 ablation therapies. The data of age, gender, histopathologic type, tumor size, and metastasis were collected. Preablation serum Tg and ATA level (Tg1 and ATA1) 6–12 months after ablation (Tg2 and ATA2) were measured. The success of ablation therapy was evaluated by diagnostic whole body scan (DxWBS) 6–12 months after ablation. There were no significant differences in age, gender, type of histopathology, tumor size, and nodal metastasis between the two groups. ATA2 ≤30 kIU/L were found in 23 (62.2%) subjects with successful ablation therapy, and ATA2 >30 kIU/L in 16 (69.6%) subjects belonged to the unsuccessful group (P = 0.017). Changes between ATA1 and ATA2 levels did not differ significantly in both the groups (P = 0.062). Tg1 <10 mg/L was found in 26 (57.8%) subjects with successful therapy (P = 0.037). Multivariate analysis showed ATA2 and Tg1 as the independent factors for the success of ablation therapy (P = 0.007 and 0.015). Adjusted odds ratio of postablation ATA was 5.379 [95% confidence interval (CI) 1.590 to 18.203] and preablation Tg was 5.822 (95% CI 1.418 to 23.902). ATA levels at 6–12 months after ablation, by considering the preablation Tg levels, is a useful marker to determine successful ablation therapy in WDTC patients with low serum Tg. Changes in serum ATA levels, although not statistically significant, can provide additional information about the course of the disease.
ABSTRAK STUDI AWAL ESTIMASI DOSIS INTERNAL 177Lu-DOTA TRASTUZUMAB PADA MANUSIA BERBASIS UJI BIODISTRIBUSI PADA MENCIT. Radiofarmaka baru untuk pengobatan penyakit kanker payudara tipe HER-2, 177Lu-DOTA Trastuzumab, telah berhasil diproduksi oleh Pusat Teknologi Radioisotop dan Radiofarmaka (PTRR) BATAN. Demi keamanan produk dan keselamatan pasien, radiofarmaka baru tersebut perlu dilengkapi dengan data studi dosis internal yang dilakukan setelah uji praklinis pada hewan coba selesai. Oleh karena itu, studi ini bertujuan untuk melakukan estimasi dosis pada pasien yang dihitung berdasarkan data uji biodistribusi pada mencit. Studi Uji biodistribusi dilakukan pada 25 ekor mencit dan diamati biodistribusinya pada organ-organ, diantaranya otak, perut, usus, jantung , ginjal, hati, paru-paru, otot, tulang, limpa dan kandung kemih. Pengamatan cacahan organ dilakukan pada jam ke 1, 2, 3, 4, 24, 48 pasca injeksi radiofarmaka 177Lu DOTA-Trastuzumab sebesar 100mCi. Hasil yang diperoleh dari uji biodistribusi adalah % ID/gram organ tikus, kemudian dilakukan konversi perhitungan ke % ID/gram organ manusia. Untuk mengestimasi dosis ke manusia, hasil %ID/gram organ tersebut dipakai sebagai input pada software dosimetri internal OLINDA/EXM, dengan cara melakukan plotting %ID/gram versus waktu, yang akan menghasilkan residence time di masing-masing organ. Setelah residence time diperoleh, dosis internal radiasi pada masing-masing organ dan seluruh tubuh dapat diketahui. Hasil studi menunjukkan bahwa tiga organ yang memiliki dosis internal tertinggi 177Lu DOTA Trastuzumab adalah : paru-paru, hati dan ovarium dengan dosis masing-masing 0,063; 0,046 dan 0,025 mSv/MBq. Disimpulkan bahwa hasil estimasi dosis internal radiasi total yang diperoleh manusia pada penyuntikan radiofarmaka 177Lu-DOTA Trastuzumab adalah 0.21 mSv/MBq. ABSTRACT INTERNAL DOSE ESTIMATION OF 177Lu-DOTA TRASTUZUMAB IN HUMAN BASED ON THE BIODISTRIBUTION DATA OF MICE: A PRELIMINARY STUDY. A new radiopharmaceutical for treating Breast Cancer of HER-2 type, 177Lu DOTA-Trastuzumab, had been successfully produced by The Centre for Radioisotope and Radiopharmaceutical Technology-BATAN. With regard to the patient safety, the new drug development process need internal dosimetry data obtained of preclinical study in animal. Hence, this study has been objected to estimate the internal radiation dose in human by performing the biodistribution test in mice. In this study, the biodistribution test was done for 25 mice and sacrificed at 1, 2, 3, 4, 24, 48 hour after the injection of 177Lu DOTA-Trastuzumab. There were 11 organs, namely brain, stomach, intestine, heart, kidneys, liver, lungs, muscle, bone, spleen, and urinary bladder, have been investigated by observing the uptake in each organ during the proposed time. The result of biodistribution test then were being calculated into injection dose per gram human organ (%ID/gr). To estimate the internal dose in human, the data of % ID/gram in human need to be plotted to calculate the residence time which will be need as the input for OLINDA/EXM, a tool for calculating internal dosimetry in Nuclear Medicine fields. As a result, three organs that have been estimated receiving the highest internal radiation dose due to the administration of 177Lu DOTA Trastuzumab are: lungs, liver, and ovaries at approximately 0,063; 0,046 and 0,025 mSv/MBq respectively. To conclude, the total internal dose in human reference model due to the administration of 177Lu-DOTA Trastuzumab has been estimated to be 0,21 mSv/MBq.
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