Determination of Iodine Uptake by Cancer Thyroid Cells with Μ-AMS and Gamma Detector
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Determination of iodine uptake by cancer thyroid cells with µ-AMS and gamma detector Ana Sofia Gusmão Gomes Thesis to obtain the Master of Science Degree in Biomedical Technologies Supervisor: Dr. Maria de Lurdes Gano Dr. Hélio Fernandes Luís Examination Committee Chairperson: Prof. Maria Margarida Fonseca Rodrigues Diogo Supervisor: Dr. Hélio Fernandes Luís Members of the committee: Prof. Maria Micaela Leal da Fonseca November of 2016 Abstract: Compared with the normal thyroid cells, thyroid cancer cells have a reduced iodine uptake. Nevertheless, radioactive iodine is the principal treatment for thyroid cancer. The aim of this dissertation is to evaluate the possibility of the use of µ-AMS as an alternative to gamma counting techniques in studies of iodine uptake in thyroid cells. For the determination of the precision and accuracy of the gamma counter used in bioassay laboratory of radiopharmaceutical group in CTN, 3 tubes with 125I solution and an activity of 0,9 µCi were prepared. These were used for the determination of the geometric effect, the reproducibility of the measurements, detection efficiency and the detection limit for 125I. In order to determine the detection limit for 129I with LATR/CTN µ-AMS system, an AgI pellet was made and measured. Another pellet, using carcinoma cells, was made to mimic the extraction of 129I by thyroid. The study allowed us to conclude that, the Berthold LB2111 can detect a minimum of 9,6x107 125I particles (4%uncertainity) compared with 2,8x105 127I particles (1% uncertainty) by µ-AMS. Since cancer cells have a lower iodine uptake than healthy cells, the better detection limit of µ-AMS is a valuable tool in the study of iodine uptake of thyroid cancer cells. This study was the first to measure iodine by µ-AMS and demonstrated the possibility of this technique to decrease the sample mass by 2 orders of magnitude when compared with conventional AMS. This will compensate the difference in primary beam intensity between the two techniques. Key-words: thyroid cancer, cells, iodine, µ-AMS, gamma detection 1. Introduction the type of counter used in this dissertation. The Well counters have a well shape, are Thyroid, the biggest endocrine organ of the extremely sensitive and commonly used for body, has a butterfly shape with two lobes, blood and urine samples, and they allow for these are connected by a strip of thyroid multiple measurements at the same time [9] tissues called isthmus. This organ releases [10]. the hormones triiodothyronine (T3) and These counters have a scintillation detector, thyroxine (T4) which control the metabolism, a photomultiplier, a pre-amplifier, an growth and maturation of our body [1] [2] [3]. amplifier, a pulse height analyser and a Differentiated thyroid cancer is the most temporizer. These are connected to a common endocrine cancer and is increasing computer which allow the visualization of the in incidence. For unclear reasons thyroid results [11] [12]. cancers occur about 3 times more often in The interaction of the incident radiation with women that in men, the risk pick is often in the detector results in the raising of the their 40-50 years. A diet low in iodine and atoms in detection material to excited states. radiation exposure are other proven risk When the atoms get back to their state level, factors of this disease [4] [5] [6]. they emit energy in the light form. These Compared with normal thyroid cells, thyroid photons are then transformed into electrical cancer cells have a reduced iodine uptake. pulses that are counted [12]. Nevertheless, beyond surgery, radioactive The Well counter has a strong geometric iodine is the principal treatment for thyroid dependence. The geometric efficiency is cancer. The main administrated radionuclide defined as the number of radiation incident is 131-odine (131I), with 8.04 days of half-life, on the detector in a given interval divided by an emission of a 606keV (maximum energy) the number emitted by the radiation source β particles and a 365 keV radiation in the same time. The geometric efficiency emission [4] [7]. decreases with increasing source-to- Because of this duality, studies of iodine detector distance. Therefore, if the sample is uptake by thyroid cells are extremely not positioned correctly in the Well detector relevant. The most used protocols for these the overall efficiency will decrease, so the studies are based on 125 iodine (125I) and on size of the sample will influence the gamma detection [8]. efficiency of the detection. Since the detector 125I has a 54.49 days half-life, 35 keV -ray has a well shape, as the sample gets bigger, emission and a 4 keV /31 keV β particles the proportion of the radiation detected by emission. It has one-third of the 131I dose, is the detector gets smaller. The ideal sample cheaper than 131I and has a longer half-life volume for the best geometric efficiency is than 131I. These are some of the reasons why 1mL [13] [14]. 125I is the main radionuclide used in thyroid On the other hand, it is not possible to uptake studies. measure samples with an activity higher Gamma counting is based on the radioactive than 37 kBq, due to the increase of the dead proprieties of the particles. Well counter is time [15]. 2 So, radioactive decay is a random process, from the sample surface. These particles emitted radiation measurements are form a secondary beam, and will be subjected to statistical fluctuations that are a analysed by the system. source of imprecision, furthermore, as said After being generated in the target chamber before Well counters are strongly dependent the secondary beam passes through the low on the sample’s size [16] [17]. energy transport system. This system transports the beam with a 10keV energy to µ-AMS is highly sensitive technique based the accelerator. on isotopic ratios measurements and not on On this system the beam passes through a radionuclides decay, which doesn’t restrict secondary Einzel, three sets of Faraday us to short half-life isotopes and gamma Cups (FC)’s and slits, deflectors plates X emission isotopes. µ-AMS uses 129I instead and Y, a low energy ESA and a low energy of 125I, a long lived isotope with 1,57x107 magnet. years of half-life [18] [19]. The LE ESA allows in one hand the vertical 129I decays with the emission of β particles and horizontal focus of the beam and on the with an energy of 154 keV and -ray other the deflection of the same. This device emission with 39keV. This isotope is usually will act as an energy filter. used to mimic 131I due to its lower dose. The LE magnet will allow the mass selection. µ-AMS measures 129I by measuring the The selected mass will be injected into the 129I/127I isotopic ratio. 127I is the only stable accelerator, which is a 3 MV Tandem iodine isotope. accelerator. This technique is a combination of two In the accelerator the beam changes its previous techniques, SIMS and AMS. It was polarity and will be accelerated. The polarity developed with the goal of combining the change process is called stripping. The capabilities of the SIMS technique in terms stripping process is the physical process by of in depth and spatial analyses of samples which the electrons in the outer shells of the with the AMS’s ability to resolve molecular atoms in the beam will be removed by the and isobaric interferences that limit the SIMS interaction with a gas, situated inside a tube technique. µ-AMS is basically a SIMS in the center of the accelerator, called the sample chamber connected to an AMS stripping channel. This process will system [20] [21]. dissociate all the molecules in the beam, µ-AMS is generally composed by an ion resolving all molecular interferences. After source, a target chamber, a beam transport the accelerator the beam will be monoatomic system, a Tandem accelerator and by a and composed of several positive charge detection system [20] [23] [24] [25]. states. The measurement in µ-AMS system starts After the accelerator, in the high energy with a negative beam production by the transport system, the beam will be analysed sputtering process. The sputtering process, again by a magnet and ESA like in the low in the µ-AMS technique, consists in energy side. This system transports the sputtering a sample with a positive beam, usually a Cs beam, extracting the particles 3 beam to the detector system, which will µL, keeping the same amount of 125I in each measure 129I. sample. The activity of each volume of the The detector system is composed by two sample was measured by the counter. different chambers. The first chamber is 2. Reproducibility composed by a FC, a PIPS detector and an ETP. The second, which is used when there Tube number 2 was measured in each of the is an isobaric interference, is an ionization detector’s channels, with the aim of verifying chamber. In this study we don’t have an the measurement’s reproducibility in all of isobaric interference, so 129I will be them. Each channel was measured 20 measured in the first chamber. times. So, since the sensitivity of the gamma 3. Linearity of the detector’s counting techniques is not enough to measure the uptake of some carcinoma response thyroid cells, the goal of this dissertation is to In order to understand the counter’s 129 measure the µ-AMS detection limit for I in reliability, and in order to calculate its order to see if it can be an alternative to the detection limit, dilutions were performed with gamma counting technique.