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1.
Lancet Oncol ; 18(11): e653-e706, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29208398

RESUMO

We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$2 billion of funding for cancer research and precision medicine. In 2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed to exploit new advances in cancer diagnosis, prevention, and treatment. Those recommendations provided a high-level view of how to accelerate the conversion of new scientific discoveries into effective treatments and prevention for cancer. The US National Cancer Institute is already implementing some of those recommendations. As experts in the priority areas identified by the BRP, we bolster those recommendations to implement this important scientific roadmap. In this Commission, we examine the BRP recommendations in greater detail and expand the discussion to include additional priority areas, including surgical oncology, radiation oncology, imaging, health systems and health disparities, regulation and financing, population science, and oncopolicy. We prioritise areas of research in the USA that we believe would accelerate efforts to benefit patients with cancer. Finally, we hope the recommendations in this report will facilitate new international collaborations to further enhance global efforts in cancer control.


Assuntos
Pesquisa Biomédica/tendências , Planejamento em Saúde/tendências , Prioridades em Saúde , National Cancer Institute (U.S.)/tendências , Neoplasias/terapia , Pesquisa Biomédica/métodos , Previsões , Humanos , Oncologia/tendências , Neoplasias/diagnóstico , Medicina de Precisão/tendências , Estados Unidos
2.
Mol Ther ; 23(6): 1110-1122, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25807290

RESUMO

Described herein is a first-in-man attempt to both genetically modify T cells with an imagable suicide gene and track these transduced donor T cells in allogeneic stem cell transplantation recipients using noninvasive positron emission tomography/computerized tomography (PET/CT) imaging. A suicide gene encoding a human CD34-Herpes Simplex Virus-1-thymidine kinase (CD34-TK75) fusion enabled enrichment of retrovirally transduced T cells (TdT), control of graft-versus-host disease and imaging of TdT migration and expansion in vivo in mice and man. Analysis confirmed that CD34-TK75-enriched TdT contained no replication competent γ-retrovirus, were sensitive to ganciclovir, and displayed characteristic retroviral insertion sites (by targeted sequencing). Affinity-purified CD34-TK75(+)-selected donor T cells (1.0-13 × 10(5))/kg were infused into eight patients who relapsed after allogeneic stem cell transplantation. Six patients also were administered 9-[4-((18)F)fluoro-3-hydroxymethyl-butyl]guanine ([(18)F]FHBG) to specifically track the genetically modified donor T cells by PET/CT at several time points after infusion. All patients were assessed for graft-versus-host disease, response to ganciclovir, circulating TdT cells (using both quantitative polymerase chain reaction and [(18)F]FHBG PET/CT imaging), TdT cell clonal expansion, and immune response to the TdT. This phase 1 trial demonstrated that genetically modified T cells and [(18)F]FHBG can be safely infused in patients with relapsed hematologic malignancies after allogeneic stem cell transplantation.


Assuntos
Antígenos CD34/imunologia , Tomografia por Emissão de Pósitrons/métodos , Transplante de Células-Tronco/métodos , Linfócitos T/imunologia , Transdução Genética , Transplante Homólogo/métodos , Animais , Antígenos CD34/genética , Antígenos CD34/metabolismo , Linhagem Celular Tumoral , Estudos de Viabilidade , Citometria de Fluxo , Ganciclovir/farmacologia , Doença Enxerto-Hospedeiro/imunologia , Guanina/administração & dosagem , Guanina/análogos & derivados , Herpesvirus Humano 1/genética , Humanos , Leucócitos Mononucleares/metabolismo , Camundongos , Células NIH 3T3 , Projetos Piloto , Linfócitos T/metabolismo , Timidina Quinase/genética , Timidina Quinase/metabolismo , Resultado do Tratamento
3.
J Nucl Med ; 63(7): 1117-1123, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35058318

RESUMO

Recent advances in the development of new molecular imaging agents for PET have led to the approval of several new molecular entities for PET imaging by the U.S. Food and Drug Administration (FDA) within the last 10 y. However, the continued use of PET drugs for diagnostic imaging procedures is reliant on a sustainable network of PET manufacturing facilities operating in accordance with the regulations for current good manufacturing practices for PET drugs (title 21, Code of Federal Regulations, part 212). With this goal in mind, a public workshop entitled "PET Drugs: A Workshop on Inspections Management and Regulatory Considerations" was held on the FDA campus in Silver Spring, MD, on February 21, 2020. The workshop was cosponsored by the FDA's Center for Drug Evaluation and Research, the Society of Nuclear Medicine and Molecular Imaging, the Medical Imaging Technology Alliance, and the World Molecular Imaging Society, in collaboration with the Coalition of PET Drug Manufacturers. The organizing committee for the workshop consisted of representatives from academic and commercial PET manufacturers as well as FDA staff members. The coauthors on this paper are all members of the workshop-organizing committee.


Assuntos
Aprovação de Drogas , Medicina Nuclear , Humanos , Preparações Farmacêuticas , Tomografia por Emissão de Pósitrons , Estados Unidos , United States Food and Drug Administration
4.
Radiol Imaging Cancer ; 4(1): e210070, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35089089

RESUMO

Fluorine 18 (18F) fluorthanatrace (18F-FTT) is a PET radiotracer for imaging poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1), an important target for a class of drugs known as PARP inhibitors, or PARPi. This article describes the stepwise development of this radiotracer from its design and preclinical evaluation to the first-in-human imaging studies and the initial validation of 18F-FTT as an imaging-based biomarker for measuring PARP-1 expression levels in patients with breast and ovarian cancer. A detailed discussion on the preparation and submission of an exploratory investigational new drug application to the Food and Drug Administration is also provided. Additionally, this review highlights the need and future plans for identifying a commercialization strategy to overcome the major financial barriers that exist when conducting the multicenter clinical trials needed for approval in the new drug application process. The goal of this article is to provide a road map that scientists and clinicians can follow for the successful clinical translation of a PET radiotracer developed in an academic setting. Keywords: Molecular Imaging-Cancer, PET, Breast, Genital/Reproductive, Chemistry, Radiotracer Development, PARPi, 18F-FTT, Investigational New Drug © RSNA, 2022.


Assuntos
Neoplasias Ovarianas , Inibidores de Poli(ADP-Ribose) Polimerases , Feminino , Humanos , Estudos Multicêntricos como Assunto , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Poli(ADP-Ribose) Polimerases/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Estados Unidos
5.
Drug Discov Today Technol ; 8(2-4): e71-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-24990265

RESUMO

Radiopharmaceuticals (RPs) have attracted tremendous interest as molecular imaging tracers in diagnostic applications and as biomarkers in drug development, in particular using Positron Emission Tomography (PET). This article summarizes important legal documents and guidelines in relation to human application of PET-RPs that pose a major challenge in implementing the full potential of this technology, thereby differentiating the US from the European situation. Regulations are reviewed with respect to licensing, conducting clinical trials and RP production - including Good Manufacturing Practice (GMP) for radioactive compounds. Professional requirements, including education, are discussed, with an outlook on future developments.:

6.
J Nucl Med ; 62(3): 422-430, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32646881

RESUMO

The Nuclear Medicine Global Initiative was formed in 2012 by 13 international organizations to promote human health by advancing the field of nuclear medicine and molecular imaging by supporting the practice and application of nuclear medicine. The first project focused on standardization of administered activities in pediatric nuclear medicine and resulted in 2 articles. For its second project the Nuclear Medicine Global Initiative chose to explore issues impacting on access and availability of radiopharmaceuticals around the world. Methods: Information was obtained by survey responses from 35 countries on available radioisotopes, radiopharmaceuticals, and kits for diagnostic and therapeutic use. Issues impacting on access and availability of radiopharmaceuticals in individual countries were also identified. Results: Detailed information on radiopharmaceuticals used in each country, and sources of supply, was evaluated. Responses highlighted problems in access, particularly due to the reliance on a sole provider, regulatory issues, and reimbursement, as well as issues of facilities and workforce, particularly in low- and middle-income countries. Conclusion: Strategies to address access and availability of radiopharmaceuticals are outlined, to enable timely and equitable patient access to nuclear medicine procedures worldwide. In the face of disruptions to global supply chains by the coronavirus disease 2019 outbreak, renewed focus on ensuring a reliable supply of radiopharmaceuticals is a major priority for nuclear medicine practice globally.


Assuntos
Internacionalidade , Medicina Nuclear/estatística & dados numéricos , Compostos Radiofarmacêuticos/provisão & distribuição , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/uso terapêutico , Tomografia Computadorizada de Emissão de Fóton Único
7.
EJNMMI Radiopharm Chem ; 4(1): 10, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31659486

RESUMO

New regulatory guidance documents from the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have recently been finalized or are in draft format outlining new pathways for preclinical safety testing. The US and the European Union appear to be moving in a similar direction focussing and refining preclinical safety data requirements for both radiodiagnostics and radiotherapeutics. We here summarize these recent documents from both the US and European perspective.

8.
J Nucl Med ; 2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30262520

RESUMO

In recent years, several new radiotracers and radionuclide therapies have been developed. There is a renaissance in nuclear medicine and molecular imaging today, for example, in terms of the ability to image and treat neuroendocrine and prostate malignancies. In order to be able to bring a new drug product from bench to bedside and assist patients, while also ensuring patient safety, stringent regulations must be met. However, differences in regulatory requirements, often based on jurisdictional politics rather than scientific evidence, can hinder global co-operation, increase expense, and slow progress. In an effort to rise above these differences, nuclear medicine advocacy organizations, regulators, and international agencies have begun to identify commonalities in the regulations to achieve harmonization. Indeed, a more streamlined approach to radiopharmaceutical drug development across jurisdictions could be achieved through establishing harmonized requirements for pre-clinical studies and manufacturing standards. This paper provides an educational overview of the regulatory and submission requirements governing investigational radiopharmaceuticals for first-in-human radiopharmaceuticals across the European and North American continents. It is hoped that through ongoing collaboration, regulatory reform and harmonization can become a reality and speed access to the most up-to-date evidence-based patient care for all.

9.
J Nucl Med ; 56(4): 497-500, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25766895

RESUMO

The Food and Drug Administration has provided a mechanism to reduce time and resources expended on new pharmaceuticals, including radiopharmaceuticals, in order to identify the most promising agents for further development. The exploratory investigational new drug guidance describes early phase 1 exploratory approaches involving microdoses of potential drug candidates that are consistent with regulatory requirements while maintaining the safety needed for human subjects, allowing sponsors to move ahead more quickly with the development of new agents.


Assuntos
Drogas em Investigação , Aplicação de Novas Drogas em Teste , Segurança do Paciente , Compostos Radiofarmacêuticos/uso terapêutico , Ensaios Clínicos Fase I como Assunto , Indústria Farmacêutica/economia , Indústria Farmacêutica/tendências , Humanos , Risco , Estados Unidos , United States Food and Drug Administration
10.
J Nucl Med ; 55(7): 1208-13, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24854794

RESUMO

The uncertain availability of (99m)Tc has become a concern for nuclear medicine departments across the globe. An issue for the United States is that currently it is dependent on a supply of (99m)Tc (from (99)Mo) that is derived solely by production outside the United States. Since the United States uses half the world's (99)Mo production, the U.S. (99)Mo supply chain would be greatly enhanced if a producer were located within the United States. The fragility of the old (99)Mo supply chain is being addressed as new facilities are constructed and new processes are developed to produce (99)Mo without highly enriched uranium. The conversion to low-enriched uranium is necessary to minimize the potential misuse of highly enriched uranium in the world for nonpeaceful means. New production facilities, new methods for the production of (99)Mo, and a new generator elution system for the supply of (99m)Tc are currently being pursued. The progress made in all these areas will be discussed, as they all highlight the need to embrace diversity to ensure that we have a robust and reliable supply of (99m)Tc in the future.


Assuntos
Molibdênio/química , Molibdênio/provisão & distribuição , Radioquímica/estatística & dados numéricos , Tecnécio/química , Tecnécio/provisão & distribuição , Órgãos Governamentais , Laboratórios , Molibdênio/economia , Radioquímica/economia , Estados Unidos
11.
J Nucl Med ; 55(7): 1132-7, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24914057

RESUMO

The Food and Drug Administration (FDA) issued the final rule for title 21 of Code of Federal Regulations part 212 regarding the regulations on current good manufacturing practice for PET drugs. The regulations are intended to ensure that PET drugs meet the safety and quality assurance requirements of the Federal Food, Drug, and Cosmetic Act. The new regulation became effective December 12, 2011, but the FDA used regulatory discretion to allow new drug applications and abbreviated new drug applications to be filed until June 12, 2012, without interruption of the existing PET drug production for human use. The production of PET drugs for both clinical use and clinical research use are outlined in this continuing education module, including an overview of specific requirements for compliance. Additionally, FDA preapproval inspections and postapproval reporting requirements are reviewed.


Assuntos
Regulamentação Governamental , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Aprovação de Drogas/economia , Aprovação de Drogas/legislação & jurisprudência , Estabilidade de Medicamentos , Honorários e Preços , Controle de Qualidade , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência
15.
J Nucl Med ; 58(5): 17N, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28461591
18.
J Nucl Med ; 57(9): 20N, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27587797
20.
PET Clin ; 5(2): 131-53, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27157669

RESUMO

The primary limitation on the development of new radiotracers for use with positron emission tomography (PET) is the time constraints created by working with radionuclides with the short half-lives inherent to carbon 11 and fluorine 18, the main radionuclides used in PET radiotracer development. In the past decade there have been several developments in the radiosynthetic methods used in PET chemistry, advances that are expected to lead to an increase in the number of radiotracers making the transition from clinical research studies to clinical PET studies. This article reviews developments in PET radiochemistry that will facilitate this process and discusses the application of these basic principles of PET radiotracer development in central nervous system research. Current status of regulatory requirements for the development of new PET radiotracers for imaging studies in humans is reviewed.

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