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.
Radiation dose to the kidneys (kidney dose) in 177 Lu-DOTATATE -Peptide Receptor Radionuclide Therapy (PRRT) is considered to be the main potential sideeffect from the treatment. Prospective assessment of kidney radiation dose can be made with SPECT, however, this requires an intensive imaging regime over a number of days. For this reason, a retrospective investigation of kidney uptake using quantitative SPECT was performed. The aim of the study was to compare the estimated radiation dose to kidneys for each cycle. Seventeen patients treated with 177 Lu-DOTATATE for metastatic neuro-endocrine tumors had full imaging for each of their treatment cycles on a Siemens Intevo SPECT/CT gamma camera. One course of treatment consisted of 3 or 4 cycles approximately 8 weeks apart spanning 6 months. SPECT/CT scans of the abdomen were acquired at 3 time points (4, 24 and 96-120 hours) after administration of ~7.8 GBq of 177 Lu-DOTATATE. Nine patients received three cycles in total and eight patients had four cycles. Volumes of interest (VOIs) were defined on a CT scan co-registered with the SPECT images and repeated over all time points, to give the radioactivity in the kidneys. Whole organ dosimetry was estimated using OLINDA/EXM using an exponential clearance model. This gives an estimate of radiation absorbed dose to kidneys, in the unit of absorbed dose of organ per administered activity (Gy/GBq) for each treatment cycle. The mean of the 3 or 4 cycles and variation can then be determined. The result shows that the average kidney radiation dose was 0.23 Gy/GBq (range: 0.06 -0.42) and the average variation between cycles for all subjects expressed as a percentage was (12.5±7.8) % (median: 11.4 %, range: 1.8 % -29.4 %). From this study, it can be concluded that the estimated radiation dose to the kidneys for PRRT shows good reproducibility (typically <20 % variation) within an individual across all cycles within one course of treatment (up to 4 cycles). The errors introduced by assuming that the dosimetry estimate per unit GBq administered from the initial cycle could be used for subsequent cycles within a course are unlikely to contribute significantly to the overall estimate of radiation burden and are considered to be safe.
STUDI AWAL ESTIMASI DOSIS INTERNAL 99mTc-MDP HASIL PRODUKSI PSTNT-BATAN PADA MANUSIA UNTUK DETEKSI METASTASIS DAN INFLAMASI TULANG BERBASIS UJI BIODISTRIBUSI HEWAN MODEL MENCIT. Kanker adalah sel abnormal yang dapat menyebar sampai ke tulang. Pemeriksaan dapat dilakukan dengan bone-scan menggunakan radiofarmaka. PSTNT-BATAN Bandung melakukan penelitian radiofarmaka penyidik tulang yaitu MDP yang dapat ditandai dengan radionuklida teknesium-99m. Penelitian ini bertujuan memperoleh estimasi dosis internal radiofarmaka 99mTc-MDP sebagai penyidik metastasis dan inflamasi tulang untuk manusia berdasarkan biodistribusi radiofarmaka 99mTc-MDP produksi PSTNT-BATAN. Metode penelitian ini, uji biodistribusi dari penandaan MDP dengan teknesium-99m dengan interval waktu 2,4,6, dan 24 jam setelah penyuntikan melalui intravena ekor pada 12 hewan model mencit normal dengan dosis injeksi 5,44 MBq tiap mencit dengan kemurnian 98,49%±25,37.Hasil uji biodistribusi didapatkan persentase dosis injeksi pergram organ hewan yang dikonversi menjadi persentase dosis injeksi pergram organ manusia yang diinput pada software OLINDA/EXM untuk mendapatkan residence time dan estimasi dosis internal. Hasil estimasi dosis menggunakan OLINDA/EXM diperoleh nilai total estimasi dosis efektif 99mTc-MDP (mSv/MBq) untuk laki-laki dewasa 1,87E-03 sedangkan untuk wanita dewasa bernilai 2,24E-03. Hasil estimasi dosis radiofarmaka 99mTc-MDP produksi PSTNT-BATAN ini dapat digunakan sebagai panduan dosis organ pada saat akan diinjeksikan pada manusia.
ABSTRAK ESTIMASI DOSIS 99mTc-GLUTATION UNTUK DIAGNOSA KANKER KEPALA DAN LEHER BERDASARKAN UJI BIODISTRIBUSI HEWAN MODEL MENCIT. 99mTc-Glutation merupakan radiofarmaka untuk mendeteksi kanker leher dan kepala. Kanker kepala dan leher terbentuk pada jaringan atau organ yang terdapat di area kepala dan leher seperti kanker hipofaring, kanker telinga, kanker kelenjar saliva, kanker mata, kanker laring, dan kanker kelenjar tiroid. Molekul Glutataion dapat berpenetrasi dengan baik didalam saluran kapiler yang mengalami inflamasi, kanker payudara serta kanker kepala dan tumor. Tujuan dari penelitian ini adalah mengetahui estimasi dosis organ radiofarmaka 99mTc-Glutation pada manusia berbasis uji biodistribusi hewan model mencit. Uji kemurnian 99mTc-Glutation dilakukan dengan menggunakan kertas kromatografi lapis tipis TLC-SG dengan fase gerak aseton kering dan larutan NaCl 0.9%. Dari hasil uji didapatkan kemurnian radiokimia sebesar 99.60 ± 0.07 %. Penelitian dilakukan pada 4 kelompok mencit dengan tiap kelompok sebanyak 3 ekor mencit. Setelah dilakukan injeksi secara intravena sebanyak 3 μCi/mL dilakukan uji biodistribusi dengan 2, 4, 6 dan 24 jam pasca injeksi dengan organ yang diteliti adalah kulit, otot, tulang, darah, usus, hati, limpa, jantung, ginjal, lambung, paru-paru, kantung kemih, dan otak. Hasil uji bidodistribusi yang diperoleh berbentuk persentase dosis injeksi per gram organ hewan, kemudian dikonversi ke persentase dosis injeksi per gram organ manusia. Hasil konversi digunakan sebagai input pada software OLINDA/EXM, menghasilkan residence time yang dapat digunakan sebagai basis perhitungan estimasi dosis 99mTc-GSH. Hasil estimasi dosis yang diperoleh adalah dosis efektif total 1,14x10-3 mSv/MBq untuk pria dan 1.34 x10-3 mSv/MBq untuk wanita. . Organ dengan estimasi dosis tertinggi adalah ginjal, sumsum dan usus dengan distribusi masingmasing organ 3.05x10-4, 2.12x10-4, dan 1.91x10-4 untuk pria dan 3.32x10-4, 2.35x10-4, dan 2.16x10-4 mSv/MBq untuk wanita. Hasil estimasi dosis ini dapat digunakan sebagai panduan dosis injeksi, namun perlu dilakukan penelitian lebih lanjut agar didapatkan estimasi dosis yang tepat Kata kunci : Radiofarmaka, dosis, glutation, uji biodistribusi, OLINDA/EXM ABSTRACT DOSE ESTIMATED 99m Tc-GLUTATION INJECTION FOR HEAD AND NECK CANCER BASED ON MICE ANIMAL MODEL BIODISTRIBUTION TEST.99mTc-Glutation is a radiopharmaceutical for the detection of head and neck cancer. Head and neck cancer is formed in tissue or organ contained in the head and neck area such as the hypopharynx cancer, ear cancer, salivary gland cancer, eye cancer, laryngeal cancer, and cancer of the thyroid gland. Glutataion can penetrate well in the capillary channel inflammatory, breast cancer and cancers of the head and tumors. The purpose of this study was to determine the estimated organ doses of radiopharmaceutical 99mTc-Glutationin humans based biodistribution test in mice. 99mTc-https://doi.
One of the important DNA repair pathways is base excision repair (BER), which plays in the human body to maintain DNA integrity, prevent cancer and DNA damage. X-ray repair cross-complementing group 1 (XRCC1) is the most important DNA repair protein in base excision repair (BER) pathways and has been reported to have a relationship with the risk of developing various cancers. The study was purposed to assess the genetic polymorphism of XRCC1 exon 6 and 10 as a risk factor for thyroid cancer. A total of 90 participants were enrolled in this study, consisted of 30 thyroid cancer patients as a case group and 60 noncancer patients as a control group. Examination of XRCC1 genotypes was carried out by using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method and statistical analysis using a Chi-square test. In this study, we reported the frequency of XRCC1 genetic polymorphism was not significantly different between cancer patients and control groups both in exon 6 and 10, and we predict that these polymorphisms were not a risk factor for thyroid cancer (P-value>0.05). In conclusion, both mutant variants of XRCC1 exon 6 and 10 are not risk factors for thyroid cancer. In further studies, it is necessary to assess genetic polymorphisms in populations with controlled non-genetic factors, such as diet, lifestyle, and environmental factors.
A lutetium 177 (177Lu) radiopharmaceutical has been used for a theragnostic agent in molecular radiotherapies. This study aimed to investigate the image quality of SPECT image from 177Lu from Jaszczak Cylindrical Phantom based on tomographic uniformity, local-sphere uniformity, and signal-to-noise ratio (SNR). Data acquisitions were conducted using a SPECT/CT unit. For contrast measurement, six hollow sphere inserts with diameters of 9.9, 12.4, 15.6, 19.7, 24.8, and 31.2 mm were filled by 177Lu with radioactivity concentration 10 times higher than the warm background. Images were reconstructed using three different iterative reconstruction algorithms, including Flash3D, OSEM2D, and Wallis. All reconstructions were carried out with the same iteration number of 4, subset number of 4, and Gaussian Filter. Results for tomographic uniformity measurement were (112.47±8.40%), (114.30±9.59%), and (105.94±17.49%) counts for Flash3D, OSEM2D, and Wallis algorithms, respectively. Flash3D algorithm provided better tomographic uniformity than others, while Wallis algorithm yielded the highest noisy image with low SNR. Local-sphere uniformity and SNR tended to significantly increase for sphere diameters larger than 19.70 mm. It was concluded that the reconstruction method significantly affects the image quality in 177Lu quantification. Then, it seems that Flash3D is the best reconstruction method for 177Lu SPECT image acquisition.
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