<p>Purpose: The aim of this thesis is to study the European (ESTRO/EAU/EORTC) and American (ABS) guidelines how to report the permanent seed implant and the most significant dosimetric parameters. It will also report on the permanent seed implant at Södersjukhuset, Karolinska University Hospital according to the guidelines. A large number of studies on pre- and post-implant dosimetry on permanent seed implants have recently been published but none is considered a standard. This makes it difficult, if not impossible, to compare data from different centres. The differences in reporting will also be discussed in this thesis. Another part of the study is to investigate how the morbidity correlates with the dose. The results in this report will give an overview of the experience at Södersjukhuset.</p><p>Matherials and Methods: This study includes 198 patients who received implants between 2004-2007 with I-125 seeds under transperineal ultrasound at Södersjukhuset (to a prescribed dose of 145 Gy). The dose-planning system VariSeed 7.1 was used with an online connection to the ultrasound system with real-time verification. Dose constraints for the planning system are V(100)>99%, V(150)>60%, V(200)>25%, UrD(10)<130% and UrD(30)<125%. Outer and inner wall of rectum was outlined for 55 patients as recommended by ESTRO/EAU/EORTC and doses to rectum were also computed.</p><p>Results: The median value for dosimetric parameters at Södersjukhuset, Karolinska University Hospital are for the prostate; D(90)=174Gy (153-194Gy), V(100)= 99% (93-100%), V(150)= 57% (40-74%), for the urethra; UrD(30) = 130% (112-147%), UrD(10) = 124% (107-142%) and for the rectum; RD2cc= 98Gy (73-128Gy), RD0.1cc=164Gy (119-240Gy), RV(100)=0.3cc (0.0-1.3cc), RV(150)=0.0cc (0.0-0.2cc). These values correspond to recommended data, except for the V(150) value. Regarding the clinically observed results, 3 patients had a relapse in their cancer, 2 patients had mild proctitis and 15 patients had urinary problems.</p><p>Discussion and Conclusions: The significant dosimetric parameters for reporting according to ESTRO/EAU/EORTC and ABS for prostate are D90[Gy], V(100)[%] and V(150)[%], for urethra are D(30) and D(10), and for rectum RD2cc and RD0.1cc. These parameters consider as a minimum to use and they further recommend secondary parameters to report. Other authors have also recommended to report RV(100) and RV(150) for rectum. This study did not show any relationship between UrD(10), UrD(30) and urinary morbidity. According to the recommendations every patient should undergo a CT-based evaluation. Further investigations are needed on whether a post-implant CT-study is necessary for real-time implantation, as there is not enough published data on this aspect.</p>

Purpose: The aim of this thesis is to study the European (ESTRO/EAU/EORTC) and American (ABS) guidelines how to report the permanent seed implant and the most significant dosimetric parameters. It will also report on the permanent seed implant at Södersjukhuset, Karolinska University Hospital according to the guidelines. A large number of studies on pre- and post-implant dosimetry on permanent seed implants have recently been published but none is considered a standard. This makes it difficult, if not impossible, to compare data from different centres. The differences in reporting will also be discussed in this thesis. Another part of the study is to investigate how the morbidity correlates with the dose. The results in this report will give an overview of the experience at Södersjukhuset. Matherials and Methods: This study includes 198 patients who received implants between 2004-2007 with I-125 seeds under transperineal ultrasound at Södersjukhuset (to a prescribed dose of 145 Gy). The dose-planning system VariSeed 7.1 was used with an online connection to the ultrasound system with real-time verification. Dose constraints for the planning system are V(100)&gt;99%, V(150)&gt;60%, V(200)&gt;25%, UrD(10)&lt;130% and UrD(30)&lt;125%. Outer and inner wall of rectum was outlined for 55 patients as recommended by ESTRO/EAU/EORTC and doses to rectum were also computed. Results: The median value for dosimetric parameters at Södersjukhuset, Karolinska University Hospital are for the prostate; D(90)=174Gy (153-194Gy), V(100)= 99% (93-100%), V(150)= 57% (40-74%), for the urethra; UrD(30) = 130% (112-147%), UrD(10) = 124% (107-142%) and for the rectum; RD2cc= 98Gy (73-128Gy), RD0.1cc=164Gy (119-240Gy), RV(100)=0.3cc (0.0-1.3cc), RV(150)=0.0cc (0.0-0.2cc). These values correspond to recommended data, except for the V(150) value. Regarding the clinically observed results, 3 patients had a relapse in their cancer, 2 patients had mild proctitis and 15 patients had urinary problems. Discussion and Conclusions: The significant dosimetric parameters for reporting according to ESTRO/EAU/EORTC and ABS for prostate are D90[Gy], V(100)[%] and V(150)[%], for urethra are D(30) and D(10), and for rectum RD2cc and RD0.1cc. These parameters consider as a minimum to use and they further recommend secondary parameters to report. Other authors have also recommended to report RV(100) and RV(150) for rectum. This study did not show any relationship between UrD(10), UrD(30) and urinary morbidity. According to the recommendations every patient should undergo a CT-based evaluation. Further investigations are needed on whether a post-implant CT-study is necessary for real-time implantation, as there is not enough published data on this aspect.

This thesis addresses the synthesis of organic compounds, some of them are derivatives of compounds with DNA binding properties, for potential use in targeted nuclide therapy. The compounds synthesized therefore also need to contain potent nuclides. Here the nuclides considered are the radionuclide 125I, and the stable isotope 10B, which becomes radioactive upon neutron activation. 125I is an Auger-electron emitter, which emits particles that can travel only about 1-2 µm through human tissue and hence has to be delivered to the cancer cell nucleus to cause DNA damage. Neutron activated 10B emits highly cell killing α-particles and 7Li3+ ions, the application of which in Boron Nuclide Capture Therapy (BNCT) has proven very promising. The thesis can be divided into three parts: i) A nido-carborate, 7-(3´-ammoniopropyl)-7,8-dicarba-nido-undecaborate(-1), has been synthesized and radioiodinated for use as a pendant group for attachment of 125I to tumor-seeking macromolecules. Radiolabeling was achieved in greater than 95% yield. ii) Both enantiomers of m-carboranylalanine, a carborane analogue of phenylalanine, have been prepared in high enantiomeric excess, and are of potential interest in BNCT. The synthesis involved amination of the N-acyl derivative formed from [3-(1,7-dicarba-closo-dodecarborane(12)-1-yl)-2-propanoic acid and Oppolzer’s camphor sultam. iii) Derivatives of the DNA intercalating compounds 9-aminoacridine, daunorubicin and doxorubicin have been synthesized and labeled with 125I. The 9-aminoacridines were synthesised with a variety of functional groups such as carboxyl, amino and hydroxyl. The anthracylines daunorubicin and doxorubicin are efficient chemotherapeutic agents; the synthesis routes of ester, amide and amine derivatives of these compounds are presented. The Chloramine T method was used for the radioiodinations, and the radioiodination precursors of both the acridine and the anthracycline derivatives, were made to contain either a trimethylstannyl group or a phenolic substituent. In the former case the trimethylstannyl group was replaced by 125I, and in the latter case, the compounds were radiolabeled directly at the o- position to the phenolic hydroxyl group. Both methods gave high radiolabeling yields.

Tyrimo tikslas - išanalizuoti priešinės liaukos vėžiu sergančių pacientų, 2007–2010 metais gydytų brachiterapija, radioaktyviojo Jodo-125 šaltinių implantavimo kokybę ir nepageidaujamą poveikį. Įvade išdėstomi tyrimo tikslai bei uždaviniai, pateikiama literatūros apžvalga, kurioje apibendrinamos pagrindinės su nagrinėjama tema susijusios problemos. Atskirame skyriuje aprašyta tyrimo metodika. Disertacijoje išnagrinėta laisvų ir skirtingais atstumais į grandinėlę sujungtų Jodo-125 šaltinių implantavimo kokybės skirtumais gydant priešinės liaukos vėžį bei dozimetrijos po implantacijos atlikimo laiko įtaką implantacijos rezultatų vertinimui. Atskirai analizuotas nepageidaujamas gydymo poveikis. Įvertinti su priešinės liaukos vėžio gydymu Jodo-125 šaltiniais susiję šlapinimosi sutrikimai, išanalizuoti erekcijos sutrikimai ir juos sukeliančtys veiksniai po Jodo-125 šaltinių implantavimo, nustatytos kraujavimo iš tiesiosios žarnos dažnio sąsajos su klinikiniais ir dozimetriniais parametrais. / Aim of this study - to analyze implant quality and treatment toxicity in prostate cancer patients, treated with Iodine-125 seeds brachytherapy during the perios of 2007 – 2010 years. Initial dissertation chapters covers study aims and objectives. Literature data about prostate brachytherapy with Iodine-125 seeds are analysed. Material and methods are thorougly described. Data about implant quality differences in prostate cancer patients, treated with loose and linked seeds, are presented. Influence of postimplant dosimetry time to evaluation of Iodine-125 implantation results is analysed. Another part of this work is dedicated to toxicity of Iodine-125 seeds brachytherapy. Various aspects of treatment side effects are evaluated urinary disorders and erectile dysfunction. Association of risk of rectal bleeding after Iodine–125 brachytherapy with clinical and dosimetry parameters is assesed.

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