Radiolabeled (R) ‐(–)‐5‐iodo‐3′‐O‐2‐(ε‐guanidinohexanoyl)‐2‐phenylacetyl‐2′‐deoxyuridine: A new theranostic for neuroblastoma

GPAID was designed to treat high ‐risk neuroblastoma, including relapsed or refractory disease. GPAID targets neuroblastoma cells in the same way as MIBG. It also cotargets DNA of proliferating cells, an attribute especially advantageous in the treatment ofMYCN‐amplified tumors. Neuroblastoma, the most common extracranial solid tumor in children, accounts for nearly 8% of childhood cancers in the United States. It is a disease with pronounced clinical and biological heterogeneities. The amplification ofMYCN, whose key tumorigenic functions include the promotion of proliferation, facilitation of the cell's entry into the S phase, and prevention of cells from leaving the cell cycle, correlates with poor prognosis. Patients with a high proliferation index disease have low survival rates. Neuroblastoma is one of the most radioresponsive of all human tumors. To exploit this radiosensitivity, radioactive guanidine (R) ‐(–)‐5‐[125I]iodo ‐3′‐O‐[2‐(ε‐guanidinohexanoyl)‐2‐phenylacetyl]‐2′‐deoxyuridine (9, GPAID) was designed. This compound enters neuroblastoma cells much like metaiodobenzylguanidine (MIBG). Additionally, it cotargets DNA of proliferating cells, an attribute especially advantageous in the treatment ofMYCN‐amplified tumors. GPAID was synthesized from the trimethylstannyl precursor with an average yield of>90% at the no ‐carrier‐added specific activities. The norepinephrine transporter‐aided delivery of GPAI...
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research

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ConclusionsAt present, there is insufficient evidence to evaluate the effects of routine surveillance imaging on survival in most pediatric extracranial solid tumors. More high ‐quality data are required, preferably through randomized controlled trials with well‐conducted qualitative elements.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Contributors : Zsuzsanna Nagy ; Yanhua Du ; Janith A Seneviratne ; Cizhong Jiang ; Glenn M MarshallSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensTo achieve the very high oncoprotein levels required to drive the malignant state, cancer cells utilise the ubiquitin proteasome system to regulate proteins involved in growth signalling pathways. Here we identify a transcriptional coactivator, ALYREF, expressed from the most common genetic copy number variation in childhood neuroblastoma, chromosome 17q21-ter gain. We show strong co-operativity between ALYREF and MYCN from tr...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research
Conclusion: RS associated with MYCN amplification, ATR loss or PARP inhibition increases sensitivity to the ATR inhibitor VE-821. These findings suggest a potential therapeutic strategy for the treatment of HR-NB.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Targeted nanocarriers entrapping microRNAs (miRNA) ‐mimics are selectively delivered to neuroblastoma cells. The technology exploits the nucleic acids negative charges to build coated cationic liposomes, which are functionalized with antibodies against GD2 receptor. The combined replenishment of miR ‐34a and let‐7b by neuroblastoma‐targeted nanoparticles exerts a cooperative down‐modulation of key oncogenes. The reactivated regulatory networks lead to a favorable therapeutic response in preclinical models. AbstractNeuroblastoma (NB) tumor substantially contributes to childhood cancer mortality. The design of nove...
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research
CONCLUSIONS: Cancer in the first stages of life is a diagnostic and therapeutic challenge due to its phenotypical diversity, its genetic load, and its therapeutic difficulties. Knowledge of its particular features is essential for its early and effective approach. PMID: 32303474 [PubMed - as supplied by publisher]
Source: Anales de Pediatria - Category: Pediatrics Authors: Tags: An Pediatr (Barc) Source Type: research
Neuroblastoma, the most common extracranial solid tumor in children, accounts for nearly 8% of childhood cancers in the United States. It is a disease with pronounced clinical and biological heterogeneities. The amplification ofMYCN, whose key tumorigenic functions include the promotion of proliferation, facilitation of the cell's entry into the S phase and prevention of cells from leaving the cell cycle, correlates with poor prognosis. Patients with a high proliferation index disease have low survival rates. Neuroblastoma is one of the most radioresponsive of all human tumors. To exploit this radiosensitivity, radioactive...
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research
Pheochromocytoma (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors associated with high cardiovascular morbidity and variable risk of malignancy. The current therapy of choice is surgical resection. Nevertheless, PCCs/PGLs are associated with a lifelong risk of tumor persistence or recurrence. A high rate of germline or somatic mutations in numerous genes has been found in these tumors. For some, the tumorigenic processes are initiated during embryogenesis. Such tumors carry gene mutations leading to pseudohypoxic phenotypes and show more immature characteristics than other chromaffin cell tumors; they are also ...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
ierkens Neuroblastoma (NBL) is the most common extracranial solid tumor in childhood. Despite intense treatment, children with this high-risk disease have a poor prognosis. Immunotherapy showed a significant improvement in event-free survival in high-risk NBL patients receiving chimeric anti-GD2 in combination with cytokines and isotretinoin after myeloablative consolidation therapy. However, response to immunotherapy varies widely, and often therapy is stopped due to severe toxicities. Objective markers that help to predict which patients will respond or develop toxicity to a certain treatment are lacking. Immunothera...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Publication date: April 2020Source: Cancer Epidemiology, Volume 65Author(s): Julie Volk, Julia E. Heck, Kjeld Schmiegelow, Johnni HansenAbstractBackgroundParental occupational exposures are suggested as contributing causes of childhood cancer.MethodsChildren age
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
Childhood cancer survivors (CCSs) from high-grade malignancies, such as high-risk neuroblastoma, have been increased, and second malignant neoplasm, becomes a serious problem for CCSs. However, detailed reports about rare types of second cancer such as gastric cancer remain limited. We herein reported a female patient who developed diffuse type gastric carcinoma after 21 years from completion of treatment to high-risk neuroblastoma. We reviewed the previous cohort studies for second gastrointestinal cancer in CCSs and the case reports with second gastric carcinoma for CCSs. We presumed second gastric cancer was refractory ...
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Clinical and Laboratory Observations Source Type: research
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