The Propensity Score Haukoos, Jason S; Lewis, Roger J
JAMA : the journal of the American Medical Association,
2015-Oct-20, Letnik:
314, Številka:
15
Journal Article
Structural imaging remains an essential component of diagnosis, staging and response assessment in patients with cancer; however, as clinicians increasingly seek to noninvasively investigate tumour ...phenotypes and evaluate functional and molecular responses to therapy, theranostics - the combination of diagnostic imaging with targeted therapy - is becoming more widely implemented. The field of radiotheranostics, which is the focus of this Review, combines molecular imaging (primarily PET and SPECT) with targeted radionuclide therapy, which involves the use of small molecules, peptides and/or antibodies as carriers for therapeutic radionuclides, typically those emitting α-, β- or auger-radiation. The exponential, global expansion of radiotheranostics in oncology stems from its potential to target and eliminate tumour cells with minimal adverse effects, owing to a mechanism of action that differs distinctly from that of most other systemic therapies. Currently, an enormous opportunity exists to expand the number of patients who can benefit from this technology, to address the urgent needs of many thousands of patients across the world. In this Review, we describe the clinical experience with established radiotheranostics as well as novel areas of research and various barriers to progress.
The advent of click chemistry has had a profound influence on almost all branches of chemical science. This is particularly true of radiochemistry and the synthesis of agents for positron emission ...tomography (PET), single photon emission computed tomography (SPECT), and targeted radiotherapy. The selectivity, ease, rapidity, and modularity of click ligations make them nearly ideally suited for the construction of radiotracers, a process that often involves working with biomolecules in aqueous conditions with inexorably decaying radioisotopes. In the following pages, our goal is to provide a broad overview of the first 10 years of research at the intersection of click chemistry and radiochemistry. The discussion will focus on four areas that we believe underscore the critical advantages provided by click chemistry: (i) the use of prosthetic groups for radiolabeling reactions, (ii) the creation of coordination scaffolds for radiometals, (iii) the site-specific radiolabeling of proteins and peptides, and (iv) the development of strategies for in vivo pretargeting. Particular emphasis will be placed on the four most prevalent click reactions-the Cu-catalyzed azide-alkyne cycloaddition (CuAAC), the strain-promoted azide-alkyne cycloaddition (SPAAC), the inverse electron demand Diels-Alder reaction (IEDDA), and the Staudinger ligation-although less well-known click ligations will be discussed as well. Ultimately, it is our hope that this review will not only serve to educate readers but will also act as a springboard, inspiring synthetic chemists and radiochemists alike to harness click chemistry in even more innovative and ambitious ways as we embark upon the second decade of this fruitful collaboration.
Radiotheranostics, injectable radiopharmaceuticals with antitumour effects, have seen rapid development over the past decade. Although some formulations are already approved for human use, more ...radiopharmaceuticals will enter clinical practice in the next 5 years, potentially introducing new therapeutic choices for patients. Despite these advances, several challenges remain, including logistics, supply chain, regulatory issues, and education and training. By highlighting active developments in the field, this Review aims to alert practitioners to the value of radiotheranostics and to outline a roadmap for future development. Multidisciplinary approaches in clinical trial design and therapeutic administration will become essential to the continued progress of this evolving therapeutic approach.
Cerenkov luminescence imaging of medical isotopes Ruggiero, Alessandro; Holland, Jason P; Lewis, Jason S ...
The Journal of nuclear medicine (1978),
07/2010, Letnik:
51, Številka:
7
Journal Article
Recenzirano
Odprti dostop
The development of novel multimodality imaging agents and techniques represents the current frontier of research in the field of medical imaging science. However, the combination of nuclear ...tomography with optical techniques has yet to be established. Here, we report the use of the inherent optical emissions from the decay of radiopharmaceuticals for Cerenkov luminescence imaging (CLI) of tumors in vivo and correlate the results with those obtained from concordant immuno-PET studies.
In vitro phantom studies were used to validate the visible light emission observed from a range of radionuclides including the positron emitters (18)F, (64)Cu, (89)Zr, and (124)I; beta-emitter (131)I; and alpha-particle emitter (225)Ac for potential use in CLI. The novel radiolabeled monoclonal antibody (89)Zr-desferrioxamine B DFO-J591 for immuno-PET of prostate-specific membrane antigen (PSMA) expression was used to coregister and correlate the CLI signal observed with the immuno-PET images and biodistribution studies.
Phantom studies confirmed that Cerenkov radiation can be observed from a range of positron-, beta-, and alpha-emitting radionuclides using standard optical imaging devices. The change in light emission intensity versus time was concordant with radionuclide decay and was also found to correlate linearly with both the activity concentration and the measured PET signal (percentage injected dose per gram). In vivo studies conducted in male severe combined immune deficient mice bearing PSMA-positive, subcutaneous LNCaP tumors demonstrated that tumor-specific uptake of (89)Zr-DFO-J591 could be visualized by both immuno-PET and CLI. Optical and immuno-PET signal intensities were found to increase over time from 24 to 96 h, and biodistribution studies were found to correlate well with both imaging modalities.
These studies represent the first, to our knowledge, quantitative assessment of CLI for measuring radiotracer uptake in vivo. Many radionuclides common to both nuclear tomographic imaging and radiotherapy have the potential to be used in CLI. The value of CLI lies in its ability to image radionuclides that do not emit either positrons or gamma-rays and are, thus, unsuitable for use with current nuclear imaging modalities. Optical imaging of Cerenkov radiation emission shows excellent promise as a potential new imaging modality for the rapid, high-throughput screening of radiopharmaceuticals.
Abstract Zirconium-89 is an attractive metallo-radionuclide for use in immuno-PET due to favorable decay characteristics. Standardized methods for the routine production and isolation of high-purity ...and high-specific-activity89 Zr using a small cyclotron are reported. Optimized cyclotron conditions reveal high average yields of 1.52±0.11 mCi/μA·h at a proton beam energy of 15 MeV and current of 15 μA using a solid, commercially available89 Y-foil target (0.1 mm, 100% natural abundance).89 Zr was isolated in high radionuclidic and radiochemical purity (>99.99%) as 89 ZrZr-oxalate by using a solid-phase hydroxamate resin with >99.5% recovery of the radioactivity. The effective specific-activity of89 Zr was found to be in the range 5.28–13.43 mCi/μg (470–1195 Ci/mmol) of zirconium. New methods for the facile production of 89 ZrZr-chloride are reported. Radiolabeling studies using the trihydroxamate ligand desferrioxamine B (DFO) gave 100% radiochemical yields in <15 min at room temperature, and in vitro stability measurements confirmed that 89 ZrZr-DFO is stable with respect to ligand dissociation in human serum for >7 days. Small-animal positron emission tomography (PET) imaging studies have demonstrated that free89 Zr(IV) ions administered as 89 ZrZr-chloride accumulate in the liver, whilst 89 ZrZr-DFO is excreted rapidly via the kidneys within <20 min. These results have important implication for the analysis of immuno-PET imaging of89 Zr-labeled monoclonal antibodies. The detailed methods described can be easily translated to other radiochemistry facilities and will facilitate the use of89 Zr in both basic science and clinical investigations.
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