Targeted Radiotheranostics: Bench to Bedside - The impact of targeted radiopharmaceuticals on oncology spans from diagnosis to therapy. Targeted diagnostic radiopharmaceuticals are molecular imaging agents labeled with a diagnostic radioisotope, allowing non-invasive characterization and assessment of the extent of disease, patient stratification, and monitoring response to treatment through tomographic imaging. Radiotherapeutics are targeted agents, labeled with a therapeutic radioisotope, that enable tumor-specific targeted radionuclide therapy (endoradiotherapy). Diagnostic and therapeutic radiopharmaceuticals based on the same molecule allow for a combined targeted theranostic approach to imaging, therapy, and response monitoring. That is we treat what we see and we see what we treat. Challenges include the complex design, synthesis and optimization of the radiopharmaceutical, and the establishment of robust syntheses for deployment to the clinic. There is a clear need for exceptional laboratory-based scientists with extensive research experience encompassing basic compound identification and optimization; preclinical evaluation; and clinical translation. I have dedicated my scientific post-graduate career for over 20 years in Dr. Sutcliffe’s laboratory (my Unit director) to the initial design-stages of agents targeting cancer-associated cell-surface receptors for positron emission tomography (PET) imaging and endoradiotherapy, including extensive chemistry and radiochemistry research; wide-ranging pre-clinical in vivo testing; through to the development of clinical grade compounds including the cGMP-synthesis of a range of radiopharmaceuticals currently under evaluation in several clinical trials under the leadership of Dr. Sutcliffe. My work was and remains instrumental for the success of Dr. Sutcliffe’s NCI and other grants, as highlighted by the 23 research publications jointly authored with her, our 2023 Society of Nuclear Medicine and Molecular Imaging Image of the Year Award - chosen from over 1500 submitted abstracts - because it “best exemplifies the most promising advances in the field of nuclear medicine and molecular imaging”, and my development and preclinical work directly leading to the 3 novel radiopharmaceuticals used in the 6 clinical imaging and therapy trials led by Dr. Sutcliffe. In this application, in close collaboration with Dr. Sutcliffe, my goals are to 1) further develop radiotheranostics with improved pharmacokinetics, 2) develop, refine and simplify radiolabeling protocols for manufacturing scale-up and wide-spread application, 3) collaboratively with other Sutcliffe lab members advance and support work on targeted theranostic peptide-conjugates to investigate their ability for cancer- specific therapy, and 4) continue to support of the current diagnostic/theranostic clinical trials targeting the cancer-associated integrin αvβ6. This award is an excellent opportunity for me to contribute to basic, translational, and clinical science. I am highly motivated by our encouraging results obtained to date and look forward to more innovative research contributions, and to improving the lives of patients with cancer.
