| 1. |
- Nilsson, Joachim N., et al.
(författare)
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Iodine avidity in papillary and poorly differentiated thyroid cancer is predicted by immunohistochemical and molecular work-up
- 2023
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Ingår i: European Thyroid Journal. - 2235-0640 .- 2235-0802. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Successful radioiodine treatment of differentiated thyroid cancer requires iodine avidity: that is, the concentration and retention of iodine in cancer tissue. Several parameters have previously been linked with lower iodine avidity. However, a comprehensive analysis of which factors best predict iodine avidity status, and the magnitude of their impact, is lacking. Methods: Quantitative measurements of iodine avidity in surgical specimens (primary tumour and lymph node metastases) of 28 patients were compared to immunohistochemical expression of the thyroid-stimulating hormone receptor, thyroid peroxidase (TPO), pendrin, sodium–iodide symporter (NIS) and mutational status of BRAF and the TERT promoter. Regression analysis was used to identify independent predictors of poor iodine avidity. Results: Mutations in BRAF and the TERT promoter were significantly associated with lower iodine avidity for lymph node metastases (18-fold and 10-fold, respectively). Membranous NIS localisation was found only in two cases but was significantly associated with high iodine avidity. TPO expression was significantly correlated with iodine avidity (r = 0.44). The multivariable modelling showed that tumour tissue localisation (primary tumour or lymph node metastasis), histological subtype, TPO and NIS expression and TERT promoter mutation were each independent predictors of iodine avidity that could explain 68% of the observed variation of iodine avidity. Conclusions: A model based on histological subtype, TPO and NIS expression and TERT promoter mutation, all evaluated on initial surgical material, can predict iodine avidity in thyroid cancer tissue ahead of treatment. This could inform early adaptation with respect to expected treatment effect.
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| 2. |
- Siikanen, Jonathan, et al.
(författare)
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A niobium water target for routine production of [(18)F]Fluoride with a MC 17 cyclotron.
- 2013
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Ingår i: Applied Radiation and Isotopes. - : Elsevier BV. - 0969-8043. ; 72C, s. 133-136
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Tidskriftsartikel (refereegranskat)abstract
- A [(18)F]Fluoride water target was constructed for a Scanditronix MC 17 cyclotron, without a beam line, with a typical wide beam of ∼30×5mm(2). Niobium was used as target chamber material. One hour irradiation with 45μA protons yields about 110GBq [(18)F]Fluoride. The saturation yield is 8.0±0.6GBq/μA (EOB). The FDG yield is 60±5% (EOS) with a TracerLab MX (G.E. Healthcare). More than 100GBq FDG is routinely produced after a 2h irradiation.
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| 3. |
- Siikanen, Jonathan, et al.
(författare)
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A Peristaltic Pump Driven Zr-89 Separation Module
- 2012
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Ingår i: 14th International Workshop on Targetry and Target Chemistry. - : AIP. - 1551-7616 .- 0094-243X. ; 1509, s. 206-210
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Konferensbidrag (refereegranskat)abstract
- To facilitate the separation of Zr-89 produced in yttrium foils, an automated separation module was designed and assembled. The module separates more than 85% of produced Zr-89 - activity in 3 g foils in less than 90 min. About 10 % remains in the dissolving vial. The quality of the separated Zr-89 activity was investigated for labeling of the HER2-binding monoclonal antibody fragment, trastuzumab-Fab.
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| 4. |
- Siikanen, Jonathan, et al.
(författare)
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A solid target system with remote handling of irradiated targets for PET cyclotrons.
- 2014
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Ingår i: Applied Radiation and Isotopes. - : Elsevier BV. - 0969-8043. ; 94, s. 294-301
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Tidskriftsartikel (refereegranskat)abstract
- A solid target system was developed for a PET cyclotron. The system is compatible with many different target materials in the form of foils and electroplated/sputtered targets which makes it useful for production of a wide variety of different PET radionuclides. The target material is manually loaded into the system. Remote handling of irradiated target material is managed with a pneumatic piston and a vacuum technique which allows the targets to be dropped into a shielded transport container. To test the target performance, proton irradiations (12.8MeV, 45μA) of monoisotopic yttrium foils (0.64mm, direct water cooling) were performed to produce (89)Zr. The yields were 2200±200MBq (1h, n=13) and 6300±65MBq (3h, n=3).
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| 5. |
- Siikanen, Jonathan, et al.
(författare)
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An anesthetic method compatible with (18)F-FDG-PET studies in mice.
- 2015
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Ingår i: American journal of nuclear medicine and molecular imaging. - 2160-8407. ; 5:3, s. 270-277
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to establish an experimental setting and an anesthetic method compatible with future sequential studies using (18)F-FDG-PET single scans, i.e. autoradiographic measurements, for the estimation of metabolic rate of glucose (MRglc) in mice. In this study we had no access to a small animal PET scanner and therefore focus was on the anesthetic setting and optimization of the input function as a preparation for the future tumor metabolic studies. Initially, four combinations of intraperitoneal (ip) anesthesia were tested on tumor bearing mice. Fentanyl-fluanisone plus diazepam yielded low and stable blood glucose levels and kept the animals sedated for approximately 2 h. The anesthesia was also tested in a longitudinal (18)F-FDG study, where tumor bearing mice were anesthetized, injected with (18)F-FDG, and sampled for blood, before, one day after, and 8 days after treatment with cisplatin. The animals were in good condition during the entire study period. To validate the method, average MRglc of whole brain and cerebellum in mice were calculated and compared with the literature. The average MRglc in the whole brain and cerebellum were 46.2±4.4 and 39.0±3.1 µmol 100g(-1) min(-1). In the present study, we have shown that an ip anesthesia with a combination of fentanyl-fluanisone and diazepam is feasible and provides stable and low blood glucose levels after a fasting period of 4 h in experiments in nude mice with xenografted human tumors. We have also verified that (18)F-FDG, intraperitoneally administrated, results in an expected plasma activity uptake and clearance. The method doesn't alter the uptake in brain which is an indirect indication that the anesthesia doesn't alter the uptake in other organs. In combination with meticulous animal handling this set-up is reliable and future sequential tumor studies of early metabolic effects with calculation of MRglc following cytotoxic therapy are made possible.
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| 6. |
- Siikanen, Jonathan
(författare)
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Radionuclide Production with PET Cyclotrons, Applications and Preclinical Experiments
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nuclear medicine is based on the radiotracer principle of George de Hevesy and the magic bullet concept by Ehrlich and focuses on the diagnosis, the treatment of diseases and the investigation of normal states within the human body using radiopharmaceuticals. A radiopharmaceutical is an atom or a chemical compound in which one or several atoms are replaced with a radionuclide. Several diagnostic and therapeutic radionuclides like 111In, 99mTc and 131I originate from nuclear reactors via a generator or direct production. But to produce many of the conventional PET radionuclides like 11C, 18F, 13N, 15O a particle accelerator like a cyclotron is necessary. Today there is a rapid increase of the research based on intact monoclonal antibodies (mAbs), engineered mAb fragments and nontraditional antibody-like scaffolds. Approved mAbs and their engineered molecules are now entering the pre-clinical and clinical platforms and both areas have opened up a need for new un-conventional radionuclides with suitable physical and chemical properties that can match all the required half-lives and decay properties set by the different molecules. With the growing interest for imaging and therapeutic nuclear medicine the demand for more and different cyclotron produced radionuclides has increased. This is verified by the increased number of cyclotrons operating in the world. In 2005, ~350 cyclotrons were estimated to be operating in those countries monitored by the International Atomic Energy Agency. A later investigation in 2014 concluded that there are currently more than 950 PET cyclotrons operating in the world. To access a broad variation of radionuclides the accelerator itself should be equipped with different target systems. The overall objective with the work described in this thesis was to increase and extend the medical radionuclide production with special focus in the design of water and solid targets for a MC 17 Scanditronix PET cyclotron. This thesis is based on the development of two targets with two applications and two preclinical experiments related to these targets.
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