Track topics on Twitter Track topics that are important to you
RESEARCH PLAN / BACKGROUND AND SIGNIFICANCE:
Tumors originating from the neuroendocrine system, although relatively rare, may be life threatening. In cases where the disease has metastasized, the 5 year survival is very poor. 131I meta-iodobenzylguanidine (MIBG)and 90Y DOTA-D-Phe1-Tyr3-Octreotide (DOTATOC) are two radiopharmaceuticals that have shown promise as therapeutic agents in patients with metastatic neuroendocrine tumors. However, delivering sufficient radiation dose to the tumor to obtain objective anti-tumor responses or cure with these radiopharmaceuticals is challenging because of the allowable dose limits imposed by radiation damage to normal tissues. Organ biodistribution and kinetics of 90Y DOTATOC and 131I MIBG are substantially different, which leads to different critical organs for these agents, the kidney for Y90Y DOTATOC and the red marrow for 131I MIBG. We propose to investigate a mechanism to increase the radiation dose delivered to tumors without exceeding "critical" radiation dose to normal organs by combining 90Y DOTATOC and 131I MIBG.
AIMS / OBJECTIVES:
The primary aim of this project is to determine, what fraction of individuals with neuroendocrine tumors would show substantially improved tumor dosimetry with combined agent therapy compared to "best" single agent therapy and determine the magnitude of the potential tumor radiation dose increase.
To achieve this, we plan to perform serial scintigraphic imaging procedures to measure patient specific bone marrow, kidney, and tumor biodistribution and kinetics for 111In Pentetreotide and 131I-MIBG in adults and children with neuroendocrine tumors. Then, using the program we have already developed, we will input the individual dosimetry measures for bone marrow, kidney and tumor to determine the optimal amounts of administered radioactivity for the combination of 131I MIBG plus 90Y DOTATOC or 131I MIBG alone.
Allocation: Non-Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic
131-I MIBG and 111-In pentetreotide, 131-I MIBG and In-111 DOTATATE
Department of Veteran Affairs Medical Center
Enrolling by invitation
University of Iowa
Published on BioPortfolio: 2014-08-27T03:14:45-0400
This study is designed to identify the best tolerated doses of Iodine-MIBG and Yttrium-DOTATOC when co-administered to treat midgut neuroendocrine tumors. These drugs (131I-MIBG, ...
The goal of this clinical research study is to learn if I-131 Metaiodobenzylguanidine (MIBG) can shrink or slow the growth of the tumor(s) in patients with metastatic neuroendocrine tumors...
The purpose of this study is to determine if High-dose 111In-Pentetreotide known as NeuroendoMedix®, is an effective treatment for Neuroendocrine Tumors.
131I-metaiodobenzylguanidine (131I-MIBG) is a norepinephrine analog that concentrates in adrenergic tissue and therefore holds promise for cell-specific treatment of neuroblastoma. This is...
This is a randomized phase II non-comparative study. Patients with gastroenteropancreatic Neuroendocrine tumour (GEP-NET) G1-G2 with progressive disease, SSR positive and FDG negative wil...
The norepinephrine transporter (NET) is essential for norepinephrine uptake at the synaptic terminals and adrenal chromaffin cells. In neuroendocrine tumors, NET can be targeted for imaging as well as...
The aim of this study was to investigate the relationship between age and uptake of fluorine-18-L-dihydroxyphenylalanine (F-DOPA) in the brain and myocardial uptake of iodine-123-metaiodobenzylguanidi...
Ga-DOTATATE, a positron-emitting somatostatin analog, has been approved by the Food and Drug Administration for imaging neuroendocrine tumors (NETs). The presence of a second primary malignancy is com...
Clinical difficulty to discriminate between the Alzheimer disease (AD) and dementia with Lewy bodies (DLB) has led researchers to focus on highly sensitive functional imaging modalities. The aim of th...
Planar whole-body imaging with I-radiolabeled metaiodobenzylguanidine (I-MIBG) is routinely used in the follow-up evaluation of neuroblastoma. In recent years, SPECT with integrated low-dose CT (SPECT...
A guanidine analog with specific affinity for tissues of the sympathetic nervous system and related tumors. The radiolabeled forms are used as antineoplastic agents and radioactive imaging agents. (Merck Index, 12th ed) MIBG serves as a neuron-blocking agent which has a strong affinity for, and retention in, the adrenal medulla and also inhibits ADP-ribosyltransferase.
Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via APUD CELLS), the presence of tumor-associated antigens, and isozyme composition.
A group of carcinomas which share a characteristic morphology, often being composed of clusters and trabecular sheets of round "blue cells", granular chromatin, and an attenuated rim of poorly demarcated cytoplasm. Neuroendocrine tumors include carcinoids, small ("oat") cell carcinomas, medullary carcinoma of the thyroid, Merkel cell tumor, cutaneous neuroendocrine carcinoma, pancreatic islet cell tumors, and pheochromocytoma. Neurosecretory granules are found within the tumor cells. (Segen, Dictionary of Modern Medicine, 1992)
A 38-kDa integral membrane glycoprotein of the presynaptic vesicles in neuron and neuroendocrine cells. It is expressed by a variety of normal and neoplastic neuroendocrine cells and is therefore used as an immunocytochemical marker for neuroendocrine differentiation in various tumors. In ALZHEIMER DISEASE and other dementing disorders, there is an important synapse loss due in part to a decrease of synaptophysin in the presynaptic vesicles.
An acidic protein found in the NEUROENDOCRINE SYSTEM that functions as a molecular chaperone for PROPROTEIN CONVERTASE 2.
Osteoporosis is a disease in which the bones become extremely porous, are subject to fracture, and heal slowly, occurring especially in women following menopause and often leading to curvature of the spine from vertebral collapse. Follow and track&n...