Targeted Alpha-Particle Radiotheraphy of Brain Tumors with 211At-81C6 Antibody
Targeted Alpha-Particle Radiotheraphy of Brain Tumors with 211At-81C6 Antibody
批准号:
8805239
负责人:
Michael Rod Zalutsky
金额:
$33.15万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2014
资助国家:
美国
项目状态:
已结题
起止时间:
2014-09-24 至 2019-08-31
关键词:
AdultAdverse effectsAlpha ParticlesAntibodiesAstatineBiologicalBrainBrain NeoplasmsBystander EffectCaliberCellsCharacteristicsChemistryChildClinicalClinical TrialsCombined Modality TherapyDiffusionDiseaseDoseDrug FormulationsEffectivenessExternal Beam Radiation TherapyExtracellular MatrixFailureGlioblastomaGlycoproteinsGoalsHalf-LifeHumanInjection of therapeutic agentInvestigationKineticsLabelLocationLong-Term SurvivorsMalignant - descriptorMalignant GliomaMalignant neoplasm of brainMaximum Tolerated DoseMinorMonoclonal AntibodiesMonoclonal Antibody 81C6NeurocognitiveNewly DiagnosedNormal tissue morphologyOutcomePatientsPhasePhase I Clinical TrialsPilot ProjectsPlayPrimary Brain NeoplasmsProceduresQuality of lifeRadiationRadiation therapyRadioactivityRadiochemistryRadioisotopesRadiolabeledReagentRecommendationRecurrenceResistanceRoleSeriesSiteSolutionsSurgically-Created Resection CavityTenascinTherapeuticTherapeutic EffectTimeTinTissuesToxic effectVariantbasebevacizumabconventional therapycytotoxiccytotoxicityexpectationimprovednovel strategiesparticlephase 1 studyphase 2 studypre-clinicalradiotracerresearch clinical testingresponsetemozolomidetherapeutic effectivenesstumortumor growthtumor progressiontumor specificity
中文摘要
目前治疗原发性恶性胶质瘤(GBM)的方法在很大程度上是不成功的
英文摘要
Current approaches for the treatment of primary malignant glioma (GBM) are largely unsuccessful, with most
GBM recurring at or adjacent to their site of origin, indicating a failure to eradicate local tumor growth;
moreover, these treatments lack tumor specificity, frequently inducing normal brain toxicity, resulting in decline
in quality of life. Our hypothesis is that these limitations can be overcome by combining a GBM reactive
monoclonal antibody (MAb) with a radionuclide emitting highly cytotoxic and focal radiation. Our clinical goal is
to evaluate the therapeutic potential of 211At-labeled anti-tenascin MAb 81C6 in newly diagnosed GBM
patients. Astatine-211 emits ¿-particles that have a greater cytotoxic effectiveness and are less susceptible to
resistance than conventional radiation, and have a range in tissue of only a few cell diameters, characteristics
that can offer important advantages for brain tumor treatment. In our pilot study performed with chimeric 81C6
(ch81C6) labeled via N-succinimidyl 3-[211At]astatobenzoate (SAB) in recurrent brain tumor patients,
encouraging responses were obtained with minimal toxicity, with 2 GBM patients surviving for nearly 3 years.
However, the maximum tolerated dose was not determined because of radiolysis-induced problems with 211At
labeling at higher activity levels. Basic radiochemistry investigations over the past few years have now yielded
a solution to this problem. In parallel, our preclinical goal is to lay the groundwork for eventual clinical
evaluation of 211At-labeled ch81C6 combined with MAb labeled with a low-energy ¿-emitter to extend the zone
of therapeutic effectiveness beyond the SCRC interface. Our Specific Aims are: 1) To complete radiochemistry
studies optimizing labeling of ch81C6 with 211At at the activity levels needed for reliable dose escalation; 2) to
conduct a Phase I/II clinical trial of 211At-labeled ch81C6 administered into the SCRC of newly diagnosed GBM
patients, with the Phase 1 study done at escalating doses of 211At (mCi) and the Phase II dose at a targeted
radiation dose (Gy) to the SCRC margins; 3) to evaluate efficacy and normal tissue toxicity of an anti-tenascin
81C6 combination therapy approach utilizing the ¿-particle emitter 211At and either the ¿-particle emitter 177Lu
or 131I.
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科研奖励(0)
会议论文
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批准号:10508057
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Radiochemistry
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批准号:8180917
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资助金额:$5.84万
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RADIOLABELING FACILITY
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批准号:7130846
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Lutetium-177 Radiolabeled Antibodies for the Treatment of CNS Malignancies
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资助金额:$21.05万
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财政年份:2004
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负责人:Michael Rod Zalutsky
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依托单位:
CORE--RADIOLABELING
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批准号:6563694
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项目类别:
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资助金额:$18.75万
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财政年份:2002
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负责人:Michael Rod Zalutsky
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依托单位:
PRETARGETING STRATEGIES FOR CENTRAL NERVOUS MALIGNANCY RADIOIMMUNOTHERAPY
-
批准号:6593432
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项目类别:
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资助金额:$31.4万
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财政年份:2002
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负责人:Michael Rod Zalutsky
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依托单位:
Astatine 211 & Radioiodine Labeled Octreotide Conjugates
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批准号:6634072
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项目类别:
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资助金额:$28.76万
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财政年份:2001
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负责人:Michael Rod Zalutsky
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依托单位:
PRETARGETING STRATEGIES FOR CENTRAL NERVOUS MALIGNANCY RADIOIMMUNOTHERAPY
-
批准号:6474096
-
项目类别:
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资助金额:$31.4万
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财政年份:2001
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负责人:Michael Rod Zalutsky
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依托单位:
PRETARGETING STRATEGIES FOR CENTRAL NERVOUS MALIGNANCY RADIOIMMUNOTHERAPY
-
批准号:6430236
-
项目类别:
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资助金额:$28.83万
-
财政年份:2001
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负责人:Michael Rod Zalutsky
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依托单位:
Astatine 211 & Radioiodine Labeled Octreotide Conjugates
-
批准号:6750143
-
项目类别:
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资助金额:$28.76万
-
财政年份:2001
-
负责人:Michael Rod Zalutsky
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依托单位:
Astatine 211 & Radioiodine Labeled Octreotide Conjugates
-
批准号:6359752
-
项目类别:
-
资助金额:$28.76万
-
财政年份:2001
-
负责人:Michael Rod Zalutsky
-
依托单位:
Astatine 211 & Radioiodine Labeled Octreotide Conjugates
-
批准号:6515153
-
项目类别:
-
资助金额:$28.76万
-
财政年份:2001
-
负责人:Michael Rod Zalutsky
-
依托单位:
CORE--RADIOLABELING
-
批准号:6477379
-
项目类别:
-
资助金额:$18.75万
-
财政年份:2001
-
负责人:Michael Rod Zalutsky
-
依托单位:
CORE--RADIOLABELING
-
批准号:6504904
-
项目类别:
-
资助金额:$18.75万
-
财政年份:2001
-
负责人:Michael Rod Zalutsky
-
依托单位:
CORE--RADIOLABELING
-
批准号:6454161
-
项目类别:
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资助金额:$18.75万
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财政年份:2001
-
负责人:Michael Rod Zalutsky
-
依托单位:
PRETARGETING STRATEGIES FOR CENTRAL NERVOUS MALIGNANCY RADIOIMMUNOTHERAPY
-
批准号:6302760
-
项目类别:
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资助金额:$18.88万
-
财政年份:2000
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负责人:Michael Rod Zalutsky
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依托单位:
PRETARGETING STRATEGIES FOR CENTRAL NERVOUS MALIGNANCY RADIOIMMUNOTHERAPY
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批准号:6354776
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项目类别:
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财政年份:2000
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负责人:Michael Rod Zalutsky
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PRETARGETING STRATEGIES FOR CENTRAL NERVOUS MALIGNANCY RADIOIMMUNOTHERAPY
-
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资助金额:$18.88万
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财政年份:1999
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负责人:Michael Rod Zalutsky
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依托单位:
海外基金