Evaluation of internal dosimetry for 225- Ac using one single measurement based on 111-In imaging

Sammanfattning: Background and aim: There is a high interest in determining the absorbed dose in tumors and organs for various radiotherapy cancer treatments. Due to limitations in today's methods of determining the patient specific absorbed dose it is usually not proceeded clinically. The methods are time consuming but also trying for patients, since it depends on several imaging procedures at different times during a time period of about seven days p.i. Therefore the aim of this thesis is to find a new method that is not as challenging for the clinic and patients, yet is as effective as the current one. The new method (1-point method) is based on single time point dosimetry for a newly developed therapy using the alpha emitting 225Ac with the help of 111In for imaging. Method: The work was divided into two parts. The first one consisted of making time activity concentration curves (TACC), based on given biokinetic data, for each organ being examined. The curves were explained either as a bi-exponential curve with uptake or without uptake. Parameters given from these curves were then used to calculate the true time integrated activity concentrations (TIAC) used as reference data. Afterwards CT-based phantoms were created after real patient data, where data from five patients was used. By using the Monte-Carlo based program SIMIND, SPECT simulations were performed at four different time points for all phantoms to calculate the TIAC with the current method (4-point method), called test data. The 4-point method is based on fitting a curve to activities quantified from four imaging procedures at different time points over the course of a week, and then integrating it. For the second part, a derivation was made to find the optimal time point (topt) when the single SPECT/CT measurement should be made to still obtain reasonable results while minimizing the uncertainties. Derivation of topt resulted in topt=1/(λ'Ac), where λ'Ac is the mean effective decay constant for each individual organ for 225Ac. Following this derivation different organs should have different optimal imaging times, since they have different biological decay constants. Therefore, simulations were performed at 96, 120 and 144 hours p.i. to test this theory. The TIAC`s obtained were then compared to reference data and the test data calculated with the 4-point method. TIAC`s for the 1-point method were given by integrating a mono-exponential curve based on the activity quantified from the single time point and a mean effective decay constant. Since 111In is our imaging radionuclide the TIAC`s were first calculated for 111In and then re-calculated for 225Ac, except for the 1-point method where the TIAC`s for 225Ac were given straight away. Results and conclusion: The results show that, for majority of the organs, the test data received with the 1-point method deviates with -4 % to 12 % from reference data for later measurements p.i. while the kidneys deviate with around 31 %. One reason being their low activity concentration around 144 hours p.i. For earlier p.i. measurements it lies around 6 % to 12 %, and for the kidneys 27 %. Thus organs with later topt had lower uncertainties at 144 hours p.i. Those with an earlier optimal imaging time, such as the kidneys, had lower uncertainties at 96 hours p.i. Similar percentages are given when deviations between the 4-point method test data and reference data are produced. Results also show that the TIAC`s received with the 1-point method test data are overestimated when compared directly to the 4-point method test data. For later p.i. measurements they deviate with about 1 % to 5 %, while for earlier p.i. measurements they deviate with about 0 % to 13 %. Therefore, depending on what accuracy one is searching for and the resources available to determine the absorbed doses, both the 4-point method and the 1-point method are successful.