New approaches to carbon-11 labeled carbonyl and thiocarbonyl groups for positron emission tomography radiotracer synthesis and development

碳-11是一种短寿命的放射性同位素，半衰期为20.3分钟，在生物化学研究、药物开发和诊断医学成像方面有着重要的应用。由于碳原子构成了所有有机化合物以及几乎所有生物分子、药物和显像剂的骨架，因此碳-11是制备这些物质的标记类似物以成像而不改变其在生命系统中的行为的最通用同位素。为了用碳-11合成显像剂，需要在严格控制的条件下快速连续高效地进行化学转化，以确保结果的可重复性和产品的安全性和实用性。我们的研究项目开发了改进的碳-11化学方法和使用这种同位素的新显像剂。具体来说，我们相信将高氧化态碳-11标签从二氧化碳和类似的衍生物（如一氧化碳和氰化物）的生产形式纳入分子的方法将极大地扩展该同位素的合成武器，并直接导致可用于增强分子成像的新型和改进的放射性药物。******我们的项目专门针对放射性标记酰胺的合成，这是在药物和蛋白质中发现的非常常见的化学键。我们将开发新的方法来制备这些对放射化学特别有用的键，包括发现使用过渡金属催化剂合成酰胺和碳-碳-11键形成的前体。这种特别有选择性的方法将使标记更复杂的分子以及组合合成成为可能。这些进步将为示踪剂的开发带来更有效的策略，因为我们可以从更简单的化学输入开始制造复杂的标记分子。最后，我们还可以制备酰胺以外的新标记分子，并追求我们的长期目标，即能够设想合成具有任何所提出的有机结构的显像剂，并开发出适用于体内成像的实用规模的方法。******作为本研究的一部分，学生将接受有机化学方面的坚实基础培训，以及短期同位素放射化学和放射性药物方法开发方面的高度专业化培训，非常适合未来在药物化学、放射药物和成像领域的职业发展。我们的实验室位于渥太华大学心脏研究所，是一个跨学科的培训环境，学员将每天与物理学、生物化学、微生物学等基础科学研究人员以及工程和医学研究人员和从业人员进行互动。我们还将积极寻求技术转让和知识产权的商业化，从我们的发现。

Carbon-11 is a short-lived radioactive isotope with a half-life of 20.3 minutes, and which has important applications for biochemistry research, drug development, and diagnostic medical imaging. Since carbon atoms form the backbone of all organic compounds and nearly all biomolecules, drugs, and imaging agents, carbon-11 is the most versatile isotope for preparing labeled analogues of these for imaging without changing their behaviour in living systems. To synthesize imaging agents with carbon-11, chemical transformations need to be performed in rapid succession with high efficiency under strictly controlled conditions to ensure reproducible results and the safety and utility of products. Our research program develops improved chemical methods with carbon-11 and new imaging agents using this isotope. Specifically, we believe that methods for incorporating high oxidation state carbon-11 labels into molecules from its production form as carbon dioxide and similar derivatives such as carbon monoxide and cyanide will greatly expand the synthetic armament for this isotope and directly lead to novel and improved radiopharmaceuticals available to power molecular imaging.******Our program is specifically targeting synthesis of radiolabeled amides, which are very common chemical bonds found in drugs and proteins. We will develop new methods to prepare these bonds in ways that are specifically useful for radiochemistry, including discovery of amide syntheses using transition metal catalysts and precursors for carbon-carbon-11 bond formation. Such particularly selective methods will enable labeling of more complex molecules as well as combinatorial syntheses. These advances will lead to a more efficient strategy for tracer development, since we can start with simpler chemical inputs to make complex labeled molecules. Finally, we can also prepare new labeled molecules beyond amides, and pursue our long-term goal of being able to envision synthesis of imaging agents bearing any proposed organic structure, and developing methods to make them on a practical scale, suitable for in vivo imaging.******As part of this research, students will undergo a strong foundation of training in organic chemistry in addition to highly specialized training in radiochemistry with short-lived isotopes and radiopharmaceutical method development, ideally suited for future careers in the medicinal chemistry, radiopharmacy, and imaging sectors. Our lab is an interdisciplinary training setting located at the University of Ottawa Heart Institute, and trainees will have daily interaction with basic science researchers in physics, biochemistry, and microbiology, as well as engineering and medical researchers and practitioners. We will also avidly pursue technology transfer and commercialization of intellectual property resulting from our discoveries.