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Contents
6(1): Pp. 20 - 27
Ada H. V. Repetto-Llamazares, Roy H. Larsen, Camilla Mollatt, Michael Lassmann and Jostein Dahle
[Open Access Plus] |
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The biodistribution of the anti-CD37 radioimmunoconjugate 177Lu-tetraxetan-tetulomab (177Lu-DOTA-HH1) was evaluated. Biodistribution of 177Lu-tetraxetan-tetulomab was compared with 177Lu-tetraxetan-rituximab and free 177Lu in nude mice implanted with Daudi lymphoma xenografts. The data showed that 177Lu-tetulomab had a relevant stability and tumor targeting properties in the human lymphoma model. The half-life of 177Lu allowed significant tumor to normal tissue ratios to be obtained indicating that 177Lu-tetraxetan-tetulomab could be suitable for clinical testing. The biological and effective half-life in blood was higher for 177Lu-tetraxetan-tetulomab than for 177Lu-tetraxetan-rituximab. The biodistribution of 177Lu-tetraxetan-tetulomab did not change significantly when the protein dose was varied from 0.01 to 1 mg/kg. Dosimetry calculations showed that the absorbed radiation doses to normal tissues and tumor in mice were not significantly different for 177Lu-tetraxetan-tetuloma b and 177Lu-tetraxetan-rituximab. The absorbed radiation doses were extrapolated to human absorbed radiation doses. These extrapolated absorbed radiation doses to normal tissues for 177Lutetraxetan- tetulomab at an injection of 40 MBq/kg were significantly lower than the absorbed radiation doses for 15 MBq/kg Zevalin, suggesting that higher tumor radiation dose can be reached with 177Lu-tetraxetan-tetulomab in the clinic.
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1(3): Pp. 251 - 253
Massimo Salvatori, Luca Indovina and Luigi Mansi
[Open Access Plus] |
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Among radionuclides usable for tumor therapy, α-particle emitters are characterized by a very high linear energy transfer (LET) resulting in a larger number of ionizations in a range corresponding to a cell diameter. Therefore, they can determine a stronger therapeutic effect compared to low LET β-particle emitters, producing their ionizations in a range up to many millimeters. In fact, because the distance between the two strands of DNA is almost the same as the distance between two ionizations of α-particles, DNA double strand breaks are induced with a high probability that finally cause cell death due to inefficient repair. Conversely, no therapeutic effect can be determined outside of concentrating sites. Therefore, the short range of α-emitters makes them powerful tools mainly when a therapeutic effect has to be reached in a restricted area, as in the elimination of minimal residual disease or in micro-metastases. Therapeutic efficacy of α-emitter radionuclides has been proven in numerous pre-clinical studies, but up to today only three main human studies are reported, including the treatment of myeloid leukemia by an anti-CD33 monoclonal antibody labelled by bismuth- 213 (213Bi), the therapy of patients with bone metastases from hormone-refractory prostate cancer by radium-223 (223Ra) and the loco-regional targeted radiotherapy with astatine-211(211At)-labelled anti-tenascin monoclonal antibody in patients with recurrent malignant brain tumours. The authors reviewed these human reported studies, evaluating perspectives, advantages and limitations of the targeted α-particle therapy.
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1(3): Pp. 203 - 208
Oyvind S. Bruland, Thora J. Jonasdottir, Darrell R. Fisher and Roy H. Larsen
[Open Access Plus] |
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The radiobiological and radiochemical properties of radium-223 (223Ra, T1/2 = 11.4 d) render this alpha-emitting radionuclide promising for targeted cancer therapy. Together with its short-lived daughters, each 223Ra decay produces four alpha-particle emissions which enhance therapy effectiveness at the cellular level. In this paper, we review the recently published data reported for pre-clinical and clinical use of 223Ra in cancer treatment. We have evaluated two distinct chemical forms of 223Ra in vivo: 1) cationic 223Ra as dissolved RaCl2, and 2) liposome-encapsulated 223Ra. Cationic 223Ra seeks metabolically active osteoblastic bone and tumor lesions with high uptake and strong binding affinity based on its similarities to calcium. Based on these properties, we have advanced the clinical use of 223Ra for treating bone metastases from breast and prostate cancer. The results show impressive anti-tumor activity and improved overall survival in hormone-refractory prostate cancer patients with bone metastases. In other studies, we have evaluated the biodistribution and tumor uptake of liposomally encapsulated 223Ra in mice with human osteosarcoma xenografts, and in dogs with spontaneous osteosarcoma and associated soft tissue metastases. Results indicate excellent biodistributions in both species. In dogs, we found considerable uptake of liposomal 223Ra in cancer metastases in multiple organs, resulting in favorable tumor- to-normal soft tissue ratios. Collectively, these findings show an outstanding potential for 223Ra as a therapeutic agent.
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1(2): Pp. 122 - 124
Kazuhiko Takatori, Myonghui Lee and Masahiro Kajiwara
[Open Access Plus] |
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Synthesis of L-[3-13C]tryptophan (2) from N,N-dimethyl[13C]formamide (4) and Dellarias oxazinone 1 as a chiral glycine equivalent was achieved. Vilsmeier reaction of indole (5) and N,N-dimethyl[13C]formamide (4) afforded a good yield of indole-3-[13C]carbaldehyde (3), which was converted to the bromide 8. Diastereoselective alkylation of the enolate of 1 with the bromide 8 proceeded with high diastereoselectivity to give 9. Ethanolysis, hydrogenolysis and hydrolysis of 9 gave L-[3-13C]tryptophan (2).
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1(2): Pp. 120 - 121
K. Iida, Y. Nakajima and M. Kajiwara
[Open Access Plus] |
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1-Amino-2-[3-13C]propanol hydrochloride (1) was synthesized by the coupling reaction of 2-phthalimidoacetyl chloride (2) with [13C]methylmagnesium iodide in the presence of copper iodide, followed by reduction with sodium borohydride and hydrolysis, in 64 % total yield from the 13C-source. All 13C- and 15N-isotopomers of 1-amino-2-propanol are now obtainable by using appropriate combinations of 13C-labeled sodium acetate, 13C- and/or 15N-labeled glycine, and potassium [15N]phthalimide.
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1(2): Pp. 62 - 64
M. Picchio, C. Messa, B. Giglioni, F. Sanvito, E. Caporizzo, C. Landoni, G. Arrigoni, A. Carretta, R. Nicoletti, P. Zannini, A. Del Maschio and F. Fazio
[Open Access Plus] |
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A case of a patient with bronchioloalveolar cell predominate lung adenocarcinoma (BAC) studied using integrated Positron Emission Tomography and Computed Tomography (PET/CT) with both 18F-fluorodeoxyglucose ([18F]FDG-PET) and [11C]Choline ([11C]Choline-PET) is described, with the aim of evaluating a new non invasive imaging method to detect and stage BAC, and providing information on tumour biology in vivo. The information derived from combining the two tracers could help in distinguishing lung adenocarcinoma with large BAC components ([18F]FDG negative and [11C]Choline positive) from inflammatory lesion ([18F]FDG and [11C]Choline positive). In addition, the simultaneous use of two PET tracers, evaluating two different metabolic pathways, together with histopathologic, immunohistochemical and gene expression analysis, could help to improve understanding of tumour in vivo behaviour.
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