Individual voxelwise dosimetry of targeted 90Y-labelled substance P radiotherapy for malignant gliomas

Kneifel, Stefan; Bernhardt, Peter; Uusijärvi, Helena; Good, Stephan; Plaßwilm, Ludwig; Buitrago-Téllez, C.; Müller-Brand, Jan; Mäcke, Helmut R.; Merlo, Adrian

doi:10.1007/s00259-006-0351-8

Cited by 25 publications

(20 citation statements)

References 24 publications

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“…In addition to the preclinical and clinical evaluation of DOTATAGA-substance P, a more sophisticated dosimetry protocol was applied to this novel therapy option (117). The aim was to establish a reproducible dosimetry for intratumoral radiopeptide therapy so that the doses of this modality could be compared with external-beam radiotherapy and the effective dose range identified.…”

Section: Radiolabeled Substance P and Chloratoxinmentioning

confidence: 99%

Radiopeptide Imaging and Therapy in Europe

Ambrosini¹,

Fani²,

Fanti³

et al. 2011

J Nucl Med

183

116

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Receptor targeting with radiolabeled peptides has become an important topic, particularly in nuclear oncology. Strong research efforts are under way in radiopharmaceutical science laboratories and in nuclear medicine departments in Europe. The target receptors belong to the large family of G-proteincoupled receptors. The prototypes of these radiopeptides are based on analogs of somatostatin targeting somatostatin receptor-positive tumors, particularly well-differentiated neuroendocrine tumors. These radiopeptides have an important impact not only on diagnosis but also on targeted radionuclide therapy of these tumors. Besides the registered radiopeptide 111 In-pentetreotide, efficient SPECT tracers labeled with 99m Tc and PET agents based on generator-produced 68 Ga have been developed and used in the clinic. In parallel to the development of diagnostic agents, radiopeptides labeled with the b 2 emitters 90 Y and 177 Lu are also widely used. Because the same chelators and therefore the same conjugates can be used in diagnosis and therapy, they constitute ideal theranostic pairs. This progress is driven not only by scientists and clinicians but also by patient interest groups. New radiopeptides targeting other G-protein-coupled receptors are entering the clinic, among them glucagon-like peptide 1 receptor-targeting molecules. This receptor is overexpressed on literally all benign insulinomas. 111 In-labeled derivatives of the insulinotropic 39-mer peptide exendin-4 were beneficial in the pre-and perioperative localization of these benign lesions. In contrast, lack of localization may indicate malignant insulinoma. The bombesin-and gastrin-releasing peptide receptor family is potentially important because these receptors are overexpressed on major human tumors such as prostate tumors, breast tumors, gastrointestinal stromal tumors, and vessels of ovarian cancer. 99m Tc-labeled peptides for SPECT and 68 Ga-, as well as 64 Cu-labeled agonists or antagonists, have been studied in breast tumors, prostate tumors, gastrointestinal stromal tumors, and gliomas with considerable success. A phase I therapeutic study with a 177 Lu-labeled agonist has been completed. There are not enough clinical data available to reveal the significance of these new modalities in patient care, but several phase I studies are under way in larger patient cohorts using PET agents. Another G-protein-coupled receptor with high overexpression on human tumors is the gastrin/ cholecystokinin-2 receptor. It is overexpressed in more than 90% of cases of medullary thyroid cancer, in small cell lung cancer, and in a subgroup of neuroendocrine tumors. Correlating with in vitro receptor localization using autoradiography of 27 patients with metastasized medullary thyroid cancer, SPECT or planar imaging of these patients resulted in a 95% sensitivity of tumor localization. Finally, another G-protein-coupled receptor is found in brain tumors and peritumoral vessels. Literally all cases of glioblastoma multiforme overexpress the neurokinin type 1 receptor; th...

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Section: Radiolabeled Substance P and Chloratoxinmentioning

confidence: 99%

Radiopeptide Imaging and Therapy in Europe

Ambrosini¹,

Fani²,

Fanti³

et al. 2011

J Nucl Med

183

116

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“…Os receptores de NK1 também estão expressos em carcinoma medular da tireóide, câncer de pulmão, pâncreas e mama. Esses receptores são raramente encontrados em tumores gastrointestinais ou linfomas (Kneifel et al, 2007;Reubi, 2003). Com isso, a SP é uma candidata potencial para utilização como molécula carregadora de um isótopo radioativo para detecção e tratamento dessas doenças.…”

Section: Lutécio-177unclassified

“…A SP radiomarcada com diferentes radionuclídeos tem sido descrita e proposta para detecção e tratamento in vivo de doenças como doença óssea inflamatória, artrite reumatóide e tumores, como carcinóides Henning et al, 2006;Kneifel et al, 2007).…”

Section: Lutécio-177unclassified

“…Se um glioma não pode ser removido cirurgicamente devido à localização crítica, emissores beta ou alfa de pequeno alcance podem ser utilizados para minimizar o dano neurológico colateral. (Kneifel et al, 2006 (Kneifel et al, 2007).…”

Section: Lutécio-177unclassified

“…Esses receptores são raramente encontrados em tumores gastrointestinais ou linfomas. Com isso, a SP torna-se uma candidata em potencial para utilização como molécula carregadora de um isótopo radioativo para detecção e tratamento dessas doenças (Reubi, 2003;Kneifel et al, 2007).…”

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Estudo da marcação e biodistribuição da substância P utilizando Lutécio-177 como radiotraçador

Lima¹

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Aos meus pais que sempre acreditaram e confiaram em mim e pelo total apoio para concluir mais esta etapa. AGRADECIMENTOSA Deus, pela vida, pela saúde, por minha família e por mais uma vez não ter me desamparado em toda a preparação para este trabalho. À minha orientadora pela grande oportunidade que me concedeu, pela confiança, pela paciência, dedicação e por sua simplicidade em transmitir seus conhecimentos.Aos bolsistas por me acolherem com tanto carinho e atenção, por cada ajuda recebida, cada ensinamento, pela troca de conhecimento, pela paciência e pela amizade construída neste período, em especial: Adriana Vidal, Akin, Camila, Priscilla e Renata. À Dra. Maria Tereza Colturato e à Dra. Tatiana Lavinias pelo apoio. A Dra. Josefina pelos seus ensinamentos e esclarecimentos. À Diretoria de Radiofarmácia -DIRF onde todos os experimentos deste trabalho foram realizados. À Miriam Suzuki pela ajuda sempre que possível para realização dos experimentos com células. À Marcela e Raquel do Centro de Desenvolvimento da Tecnologia Nuclear (CDTN-MG) pela doação das células tumorais U-87 MG. À Neide do Biotério por disponibilizar os animais para os ensaios. À colaboração dos colegas da DIRF em especial: Idelí, Nathanael e Vivian. A toda minha família por todo o estímulo recebido, em especial: Claudionor e Patrícia, Claudia e Rubens, Claudete, sobrinhos, Tio Geraldo e Tia Margarida. Às minhas amigas: em especial Adriana Siqueira, por sempre me apoiar, acreditar nos meus sonhos e por sua amizade incondicional e Marcela pelas aulas de inglês. Aos colegas de trabalho: RESUMO Gliomas malignos são tumores cerebrais primários, resistentes a vários tratamentos, como quimioterapia, radioterapia, indução de apoptose e cirurgia. Uma alternativa para o tratamento dos gliomas malignos é a terapia radionuclídea. Essa técnica ABSTRACT Malignant gliomas are primary brain tumors, resistant to various treatments, as chemotherapy, radiotherapy, induction of apoptosis and surgery. An alternative for the treatment of malignant gliomas is the radionuclide therapy. This technique apply radiolabeled molecules that selectively bind to tumor cells producing cytotoxic effect by dose irradiation, and resulting in death of tumor cells. Most protocols for radionuclide therapy of malignant brain tumors involve the administration of peptides labeled with β emitting radioisotopes. The Substance P (SP) is an 11-amino acid neuropeptide, characterized by the C-terminal sequence Phe-X-Gly-Leu-Met-NH 2 . The use of SP labeled with different radionuclides including 177 Lu, have been proposed for in vivo treatment of tumors. SP is the most important target of neurokinin 1 receptors, overexpressed in malignant gliomas. The objective of this work was to study conditions of radiolabeling DOTA-SP with 177 Lu, the stability of labeled compound and in vivo and in vitro, to develop a protocol production and evaluate the potential of the radiopharmaceutical in the therapy of gliomas. The labeling conditions were optimized varying the temperature, reaction time, activity ...

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DOTAGA–Anhydride: A Valuable Building Block for the Preparation of DOTA‐Like Chelating Agents

Bernhard

Moreau

Lhenry

et al. 2012

Chemistry A European J

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A DOTA derivative that contains an anhydride group was readily synthesized by reacting DOTAGA with acetic anhydride and its reactivity was investigated. Opening the anhydride with propylamine led to the selective formation of one of two possible regioisomers. The structure of the obtained isomer was unambiguously determined by 1D and 2D NMR experiments, including COSY, HMBC, and NOESY techniques. This bifunctional chelating agent offers a convenient and attractive approach for labeling biomolecules and, more generally, for the synthesis of a large range of DOTA derivatives. The scope of the reaction was extended to prepare DOTA-like compounds that contained various functional groups, such as isothiocyanate, thiol, ester, and amino acid moieties. This versatile building block was also used for the synthesis of a bimodal tag for SPECT or PET/optical imaging.

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Individual voxelwise dosimetry of targeted 90Y-labelled substance P radiotherapy for malignant gliomas

Cited by 25 publications

References 24 publications

Radiopeptide Imaging and Therapy in Europe

Radiopeptide Imaging and Therapy in Europe

Estudo da marcação e biodistribuição da substância P utilizando Lutécio-177 como radiotraçador

DOTAGA–Anhydride: A Valuable Building Block for the Preparation of DOTA‐Like Chelating Agents

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