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- Andersson, Lise-Lotte, et al.
(författare)
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Extensive Gamma-ray Spectroscopy of Normally and Superdeformed Structures in 61Cu
- 2008
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 36:3, s. 251-278
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Tidskriftsartikel (refereegranskat)abstract
- A largely extended experimental knowledge of the Cu-61(29)32 nucleus has been obtained from three experiments. Excited states in Cu-61 were produced via the fusion-evaporation reaction Si-28(Ar-36, 3p)Cu-61. In addition to the Ge array GAMMASPHERE, neutron and charged-particle detectors placed around the target position were used for high-performance particle spectroscopy. The constructed level scheme includes more than 160 energy levels and 320 gamma-ray transitions belonging to both normally deformed as well as superdeformed rotational structures. The multipolarities have been determined for the gamma-ray transitions and as a result spin-parity assignments are given for nearly all energy levels. Experimental results in the normally deformed region are compared with predictions from large-scale shell model calculations. The collective structures are compared with results from cranked Nilsson-Strutinsky calculations. The results reveal the need to modify the standard Nilsson parameters in the mass A similar to 60 region.
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4. |
- Carlsson, Jörgen, 1944-
(författare)
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Developmental trends in targeted radionuclide therapy : Biological aspects
- 2008
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Ingår i: Targeted Radionuclide Tumor Therapy. - New York : Springer. - 9781402086953 ; , s. 387-398
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Bokkapitel (populärvet., debatt m.m.)abstract
- Targeted radionuclide therapy of hematopoietic malignancies in the clinical setting has been achieved and similar successes with solid tumors and cells disseminated from them are likely within reach. Recombinant technologies have led to the development of a number of new targeting agents and the evaluation of a number of putative new targets is currently in progress. These advances are currently under evaluation in the preclinical setting and are expected to transition into clinical trials before long. Many of these new agents exhibit both improved pharmacological properties and enhanced cellular retention, both of which may lead to substantial improvements over existing compounds. In addition, our knowledge of basic radiobiology and its impact on the different modes of cell death is rapidly expanding, leading to new understanding in the fundamental differences between hematopoietic and epithelial tumor cells. Such knowledge will likely have a significant influence on the development of future treatment modalities. Furthermore, the complex interactions between radiation induced intracellular signaling pathways and the crucial observation that low dose radiation (e.g. less than 15 Gy) is able to significantly affect the growth of disseminated solid tumors cells suggests to us that a new era in targeted radionuclide therapy may soon be here.
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5. |
- Carlsson, Jörgen
(författare)
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Effects of low dose-rate radiation on cellular survival
- 2008
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Ingår i: Targeted Radionuclide Tumor Therapy. - New York : Springer. - 9781402086953 ; , s. 295-310
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Bokkapitel (populärvet., debatt m.m.)abstract
- The experience of external radiotherapy can only to a limited extent be used to understand therapeutic effects of radionuclide therapy. A major difference is that the dose-rate at radionuclide therapy is at least two orders of magnitude lower. Part of this chapter deals with estimates of the necessary dose-rate and exposure time in combination in order to deliver therapeutic effects to tumour cells. It is proposed that combinations of about 0.1–0.2 Gy/h for several days or about 1 Gy/h for at least 1 day is necessary. Such dose-rates can be achieved with the help of cross fire radiation. Effects of radionuclide therapy in terms of apoptosis, cell-cycle blocks and hyperradiosensitivity are also discussed.
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6. |
- Carlsson, Jörgen, 1944-
(författare)
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EGFR-family expression and implications for targeted radionuclide therapy
- 2008
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Ingår i: Targeted Radionuclide Therapy. - New York : Springer. - 9781402086953 ; , s. 25-58
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Summary High expression in the primary tumor of receptors in the EGFR-family is most often also accompanied by a similar high expression in corresponding metastases. This makes these receptors interesting as putative targets for targeted radionuclide therapy of metastases and disseminated tumor cells. The expression of all four family members, EGFR, HER2, HER3 and HER4 is reviewed in this chapter. Studies on breast, urinary bladder, colorectal, prostate, head and neck, esophageal and glioma tumors are described and possible strategies for targeted radionuclide therapy are discussed. Quantification of receptor expression and the possible influence of genomic stability on the expression are also discussed.
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7. |
- Carlsson, Jörgen
(författare)
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Introduction to radionuclide therapy
- 2008
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Ingår i: Targeted Radionuclide Tumor Therapy. - New York : Springer. - 9781402086953 ; , s. 1-11
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This introductory chapter is written for those who are new to the field and desire a short overview of the present status of clinical and preclinical radionuclide therapy. In particular, this chapter provides an overview of the radiophysical concepts and key aspects of dosimetry and treatment planning that are beyond the scope of this book’s focus on biological aspects of radionuclide therapy. Finally, a discussion on the choice of radionuclides and the availability of radiopharmaceuticals is provided.
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8. |
- Carlsson, Jörgen, et al.
(författare)
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Penetration of tumor therapy interesting substances in non-vascularized metastases. : Review of studies in multicellular spheroids
- 2006
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Ingår i: Current Cancer Therapy Reviews. - : Bentham Science Publishers Ltd.. - 1573-3947. ; 27, s. 293-304
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Tidskriftsartikel (refereegranskat)abstract
- Penetration properties, studied in multicellular spheroids, of totally 23 radiolabeled or boronated substances are summarized. The spheroids were models for small non-vascularized metastases, and there is special emphasis on results obtained with a freeze-drying method. The substances were detected using autoradiography or neutron capture radiography. Certain substances, e.g. 5-FU, glucose, BSH and one antibody , penetrated efficiently, while others, e.g. vinblastine, an epidermal growth factor derivative, and two other types of antibodies only penetrated into the outer periphery of the spheroids in spite of long incubation time. The molecular weight of the substances did not relate well with the penetration properties. Instead, those substances that bound extensively had in most cases limited penetration. This was, for example, clearly shown for the drug Ara-C when applied to two different types of spheroids, one type giving low binding and good penetration and one giving extensive binding and less penetration. The penetration of an antibody and an EGF-derivative improved significantly when their binding sites were blocked. It is concluded that molecular weight is not a dominating determinant for penetration in the studied model, but that binding is. Such knowledge is valuable for the understanding of effects of chemotherapy, targeted radionuclide therapy and immunotherapy and for the development of new agents for such therapies.
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9. |
- Carlsson, Jörgen, et al.
(författare)
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Planning for intracavitary anti-EGFR radionuclide therapy of gliomas : Literature review and data on EGFR expression
- 2006
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Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 77:1, s. 33-45
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Tidskriftsartikel (refereegranskat)abstract
- Targeting with radionuclide labelled substances that bind specifically to the epidermal growth factor receptor, EGFR, is considered for intracavitary therapy of EGFR-positive glioblastoma multiforme, GBM. Relevant literature is reviewed and examples of EGFR expression in GBM are given. The therapeutical efforts made so far using intracavitary anti-tenascin radionuclide therapy of GBM have given limited effects, probably due to low radiation doses to the migrating glioma cells in the brain. Low radiation doses might be due to limited penetration of the targeting agents or heterogeneity in the expression of the target structure. In this article we focus on the possibilities to target EGFR on the tumour cells instead of an extracellular matrix component. There seems to be a lack of knowledge on the degree of intratumoral variation of EGFR expression in GBM, although the expression seemed rather homogeneous over large areas in most of the examples (n=16) presented from our laboratory. The observed homogeneity was surprising considering the genomic instability and heterogeneity that generally characterises highly malignant tumours. However, overexpression of EGFR is, at least in primary GBMs, one of the steps in the development of malignancy, and tumour cells that lose or downregulate EGFR will probably be outgrown in an expanding tumour cell population. Thus, loss of EGFR expression might not be the critical factor for successful intracavitary radionuclide therapy. Instead, it is likely that the penetration properties of the targeting agents are critical, and detailed studies on this are urgent.
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10. |
- Carlsson, Jörgen, et al.
(författare)
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Requirements regarding dose rate and exposure time for killing of tumour cells in beta particle radionuclide therapy
- 2006
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 33:10, s. 1185-1195
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to identify combinations of dose rate and exposure time that have the potential to provide curative treatment with targeted radionuclide therapy applying low dose rate beta irradiation. Methods: Five tumour cell lines, U-373MG and U-118MG gliomas, HT-29 colon carcinoma, A-431 cervical squamous carcinoma and SKBR-3 breast cancer, were used. An experimental model with 10(5) tumour cells in each sample was irradiated with low dose rate beta particles. The criterion for successful treatment was absence of recovery of cells during a follow-up period of 3 months. The initial dose rates were in the range 0.1-0.8 Gy/h, and the cells were continuously exposed for 1, 3 or 7 days. These combinations covered dose rates and doses achievable in targeted radionuclide therapy. Results: Continuous irradiation with dose rates of 0.2-0.3 and 0.4-0.6 Gy/h for 7 and 3 days, respectively, could kill all cells in each tumour cell sample. These treatments gave total radiation doses of 30-40 Gy. However, when exposed for just 24 h with about 0.8 Gy/h, only the SKBR-3 cells were successfully treated; all the other cell types recovered. There were large cell type-dependent variations in the growth delay patterns for the cultures that recovered. The U-118MG cells were most resistant and the U-373MG and SKBR-3 cells most sensitive to the treatments. The HT-29 and A-431 cells were intermediate. Conclusion: The results serve as a guideline for the combinations of dose rate and exposure time necessary to kill tumour cells when applying low dose rate beta irradiation. The shift from recovery to "cure" fell within a narrow range of dose rate and exposure time combinations.
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