| 1. |
- Forrer, Flavio, et al.
(författare)
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Treatment with 177Lu-DOTATOC of patients with relapse of neuroendocrine tumors after treatment with 90Y-DOTATOC.
- 2005
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 46:8, s. 1310-6
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Tidskriftsartikel (refereegranskat)abstract
- Therapy with [(90)Y-DOTA(0), Tyr(3)]-octreotide (DOTATOC, where DOTA = tetraazacyclododecane tetraacetic acid and TOC = D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr(ol)) is established for the treatment of metastatic neuroendocrine tumors. Nevertheless, many patients experience disease relapse, and further treatment may cause renal failure. Trials with (177)Lu-labeled somatostatin analogs showed less nephrotoxicity. We initiated a prospective study with (177)Lu-DOTATOC in patients with relapsed neuroendocrine tumors after (90)Y-DOTATOC treatment. METHODS: Twenty-seven patients, pretreated with (90)Y-DOTATOC, were included. The mean time between the last treatment with (90)Y-DOTATOC and (177)Lu-DOTATOC was 15.4 +/- 7.8 mo (SD). All patients were injected with 7,400 MBq of (177)Lu-DOTATOC. Restaging was performed after 8-12 wk. Hematotoxicity or renal toxicity of World Health Organization grade 1 or 2 was not an exclusion criterion. RESULTS: Creatinine levels increased significantly, from 66 +/- 14 micromol/L to 100 +/- 44 micromol/L (P < 0.0001), after (90)Y-DOTATOC therapy. The mean hemoglobin level dropped from 131 +/- 14 to 117 +/- 13 g/L (P < 0.0001) after (90)Y-DOTATOC therapy. (177)Lu-DOTATOC therapy was well tolerated. No serious adverse events occurred. The mean absorbed doses were 413 +/- 159 mGy for the whole body, 3.1 +/- 1.5 Gy for the kidneys, and 61 +/- 5 mGy for the red marrow. After restaging, we found a partial remission in 2 patients, a minor response in 5 patients, stable disease in 12 patients, and progressive disease in 8 patients. Mean hemoglobin and creatinine levels did not change significantly. CONCLUSION: (177)Lu-DOTATOC therapy in patients with relapse after (90)Y-DOTATOC treatment is feasible, safe, and efficacious. No serious adverse events occurred.
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| 2. |
- Uusijärvi, Helena, 1979, et al.
(författare)
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Electron- and positron-emitting radiolanthanides for therapy: aspects of dosimetry and production.
- 2006
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 47:5, s. 807-14
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Tidskriftsartikel (refereegranskat)abstract
- All lanthanides have similar chemical properties regarding labeling. Therefore, radiolanthanides that have been used for therapy, such as (153)Sm and (177)Lu, might easily be replaced with other radiolanthanides. The aim of this work was to investigate the suitability of electron- and positron-emitting radiolanthanides for radionuclide therapy with reference to dosimetry and production possibilities. METHODS: Radiolanthanides with half-lives of 1 h to 15 d, stable or long-lived daughters, and limited photon emission were selected. The ratio of the absorbed dose rate to the tumors and the normal tissue (TND) was calculated for different tumor sizes and compared with the TND values for (90)Y and (131)I. The normal tissue and tumors were simulated as an ellipsoid and spheres, respectively. The TND values depend on the physical parameters of the radionuclides, the tumor size, and the ratio between the activity concentrations in the tumor and normal tissue (TNC). RESULTS: (153)Sm, (161)Tb, (169)Er, (175)Yb, and (177)Lu had the highest TND values for most of the tumor sizes studied. Among these radiolanthanides, (161)Tb and (177)Lu are the only ones that can be produced no-carrier-added (nca) and with high specific activities. The Auger-electron emitters (161)Ho and (167)Tm had high TND values for tumors weighing less than 1 mg and can be produced nca and with high specific activities. (142)Pr, (145)Pr, and (166)Ho showed TND values similar to those of (90)Y. (166)Ho is generator produced and can be obtained nca and at high specific activities. (143)Pr, (149)Pm, (150)Eu, (159)Gd, (165)Dy, (176m)Lu, and (179)Lu had higher TND values than did (90)Y for all tumor sizes studied, but only (149)Pm can be produced nca and at high specific activities. The other electron-emitting radiolanthanides and the positron-emitting radiolanthanides showed low TND values for all tumor sizes because of the high photon contribution. CONCLUSION: The low-energy electron emitters (161)Tb, (177)Lu, and (167)Tm might be suitable for radionuclide therapy. The Auger-electron emitter (161)Ho might not be suitable for systemic radionuclide therapy (intravenous injection) because of its short half-life but might be suitable for local therapy (e.g., in body cavities). If higher electron energy is needed, (149)Pm or (166)Ho might be suitable for radionuclide therapy.
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| 3. |
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| 4. |
- Velikyan, Irina, 1966-
(författare)
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Synthesis, Characterisation and Application of 68Ga-labelled Macromolecules
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The positron emitting radionuclide 68Ga (T1/2 = 68 min) might become of practical interest for clinical positron emission tomography (PET). The metallic cation, 68Ga(III), is suitable for complexation with chelators, either naked or conjugated with biological macromolecules. Such labelling procedures require pure and concentrated preparations of 68Ga(III), which cannot be sufficiently fulfilled by the presently available 68Ge/68Ga generator eluate. This thesis presents methods to increase the concentration and purity of 68Ga obtained from a commercial 68Ge/68Ga generator. The use of the preconcentrated and purified 68Ga eluate along with microwave heating allowed quantitative 68Ga-labelling of peptide conjugates within 15 min. The specific radioactivity of the radiolabelled peptides was improved considerably compared to previously applied techniques using non-treated generator eluate and conventional heating. A commercial 68Ge/68Ga generator in combination with the method for preconcentration/purification and microwave heated labelling might result in an automated device for 68Ga-based radiopharmaceutical kit production with quantitative incorporation of 68Ga(III).Macromolecules were labelled with 68Ga(III) either directly or via a chelator. The bifunctional chelator, DOTA, was conjugated in solution to peptides, an antibody and oligonucleotides. The peptides had varied pI values, constitution, and length ranging from 8 to 53 amino acid residues. The oligonucleotides were of various sequences and length with modifications in backbone, sugar moiety and both 3' and 5' ends with a molecular weight up to 9.8 kDa. The bioconjugates were labeled with 68Ga(III), and the resulting tracers were characterised chemically and biologically. The identity of the 68Ga-labelled bioconjugates was verified. The tracers were found to be stable and their biological activity maintained. Specific radioactivity was shown to be an important parameter influencing the feasibility of accurate imaging data quantification.Furthermore, 68Ga-labelled peptide imaging was shown to be a useful tool to study peptide adsorption to microstructures in a chemical analysis device.
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| 6. |
- Öberg, Kjell, et al.
(författare)
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A Delphic consensus assessment : imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management
- 2016
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Ingår i: Endocrine Connections. - 2049-3614. ; 5:5, s. 174-187
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Tidskriftsartikel (refereegranskat)abstract
- The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors) criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin); monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33) assessed current imaging strategies and biomarkers in NEN management. Consensus (>75%) was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest) had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA) would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.
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