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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.

Nuclear medicine is the branch of medicine that introduces radioactive substances into the human body to diagnose and treat diseases. After introduction, the radioactive substance concentrates in some portion of the target organ or tissue based on its physiological and biological properties. The gamma rays that it emits pass through the body and can be translated by a gamma camera and computer into two- or three-dimensional images of the concerned organ. Positron Emission Tomography (PET) radionuclides introduced into the body decay into positrons that collide with electrons to produce two parallel and opposing rays. A circular series of detectors around the body capture the emissions, giving a more accurate picture than that given by a single gamma ray.

Purpose: Cu-diacetyl-bis(N4-methylthiosemicarbazone (Cu-ATSM) is an effective marker for the delineation of hypoxic tissue. Dosimetry calculations by the established Medical Internal Radionuclide Dose (MIRD) approach were performed with both animal and patient data. Methods: Human absorbed dose estimates extrapolated from rat data were based on the biodistribution of 61Cu-ATSM in adult rats. Eighteen tissues were harvested and time-activity curves generated. The measured residence times and the MIRD S-values for 60Cu-ATSM were used to estimate human absorbed doses. The biodistribution of the tracer was directly measured in five patients injected with approximately 480 MBq of 60Cu-ATSM and imaged by positron emission tomography (PET) with a whole-body protocol. The combined data from all patients were used to derive organ residence times, and organ doses were calculated by MIRD methodology for 60Cu-ATSM, 61Cu-ATSM, 62Cu-ATSM, and 64Cu-ATSM. Results: Human absorbed dose estimates extrapolated from rat biodistribution data indicated that the kidneys appeared to be the dose-limiting organ (0.083 mGy/MBq) with a whole-body dose of 0.009 mGy/MBq. Based on the human PET imaging data, the liver appeared as the dose-limiting organ, with an average radiation dose of 0.064 mGy/MBq. The whole-body dose was 0.009 mGy/MBq and the effective dose was 0.011 mSv/MBq. Conclusion: These relatively small absorbed doses to normal organs allow for the safe injection of 500-800 MBq of 60Cu-ATSM, which is sufficient for PET imaging in clinical trials. [ABSTRACT FROM AUTHOR]

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 × 105)/kg were infused into eight patients who relapsed after allogeneic stem cell transplantation. Six patients also were administered 9-[4-(18F)fluoro-3-hydroxymethyl-butyl]guanine ([18F]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 [18F]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 [18F]FHBG can be safely infused in patients with relapsed hematologic malignancies after allogeneic stem cell transplantation. [ABSTRACT FROM AUTHOR]

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., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Fluorine 18 ( 18 F) fluorthanatrace ( 18 F-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 18 F-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, 18 F-FTT, Investigational New Drug © RSNA, 2022.

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., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)