Mark Goodman: The Radiologist

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Mark Goodman, PhD holds the Emory University Endowed Chair in Imaging Science. He is Professor in the Department of Radiology and Imaging Sciences, Department of Psychiatry and Behavioral Sciences and Department of Hematology and Medical Oncology and Director of the Radiology and Imaging Sciences Radiopharmaceutical Discovery Laboratory. Goodman received his BA in chemistry from Monmouth College, Illinois, and a PhD from the University of Alabama, Tuscaloosa. He trained as a postdoctoral fellow at Yale and Harvard University in radiopharmaceutical chemistry. His research is directed towards the development of new radiotracers for the study and management of treatment of myocardial disorders, cancer, bacterial infections, cocaine addiction, mood, and psychomotor disorders.

What drew you to research in radiology and imaging sciences?

After I received my Ph.D. in organic chemistry, I knew I wanted to embark on a career in medicinal chemistry. During my postdoctoral training, I became aware of a field called nuclear medicine. I became interested in it. There was an NIH traineeship in the Department of Radiology at Massachusetts General Hospital at Harvard that applied organic chemistry to preparing radioactive drugs to image disease. I spent two years learning about the field and about cyclotron-produced radioelements that can be tagged to active organic molecules. That’s what got me interested radiology and imaging sciences.

What is a radiolabeled imaging agent?

A radiolabeled imaging agent is a biologically active molecule that, when administered to the body, goes to a specific organ or lesion based upon a biochemical process that is occurring in that organ or lesion. It’s administered intravenously and travels through the circulatory system and binds to its target. It clears away from the background that would mask detection through imaging. We get quantitative data from this imaging procedure that allows you to measure the interaction of the radiolabeled compound with its molecular binding site or biochemical process such as an enzyme reaction. This gives you knowledge that hopefully allows you to diagnose the disease by proving it’s there. In the case of FACBC, the imaging agent is an amino acid.

What are the drawbacks of traditional PET imaging when it comes to detecting prostate cancer?

The biggest shortcoming with imaging prostate cancer is that most imaging agents are excreted through the urinary system. Radioactivity accumulates in the bladder quite rapidly, and that gives a very high radioactive background that does not allow you to visualize a tumor in the prostate or proximal to it. This can be addressed by inserting a Foley catheter in the bladder and emptying radioactive urine, but this is an uncomfortable and invasive process. It would be more ideal if one had an imaging agent that did not accumulate in the bladder with any significant degree but accumulated in the cancer in the prostate, or lymph nodes that are proximal to the prostate. FACBC happens to be the unique molecule that allows you to do this.

Can you describe the discovery process for FACBC?

In 1993, Emory recruited me to establish a research radiochemistry program to oversee the production of known imaging agents for human research and clinical diagnosis, and to develop new ones. That’s how FACBC was discovered. It was one of the projects that my lab worked on to develop an F-18 amino acid that could be used to study gliomas and systemic cancers. When I was at the University of Tennessee at Knoxville, I was working with a carbon-11 amino acid. We called it carbon-11 ACBC. It’s a cyclic amino acid that has both an amine group and a carboxylic acid group. You can radiolabel the carboxylic acid group with carbon-11. When I came to Emory, I wanted to see if I could adapt the molecule to label it with a radioelement called fluorine-18. The difference between carbon-11 and fluorine-18 is that carbon-11 has a half-life of 20 minutes, which means that every 20 minutes the radioactivity decays to half the amount. Fluorine-18 has 110-minute half-life, so takes longer for the radioactivity to decay away. Fluorine-18 is also a very desirable radioelement because you can make it in large amounts on small medical cyclotrons. That way, if you had a product, you could distribute it to many hospitals or research centers from a single production place. We labeled the molecule with fluorine-18 and we first studied it in rodents that had implanted brain tumors. We then compared it to the standard radiolabeled cancer imaging agent called fluorine-18 labeled 2-fluoro-2-deoxyglucose, 2-FDG. Our molecule mimicked the carbon-11 ACBC and showed good brain tumor uptake and 6-to-1 contrast with normal brain tissue which was superior to 2-FDG’s properties. We translated the fluorine-18 FACBC to humans with malignant gliomas and observed the same high tumor to brain ratios.

Can you walk me through the process of how a patient is treated with FACBC?

If a patient has had prostate cancer and the treatment that is decided upon is for the patient is to get a prostatectomy, the prostate-specific antigen (PSA), a protein produced by prostate cancer, post-operation should be almost undetectable. If the PSA becomes detectible and increases over time, you can do an FACBC scan to see if there is prostate cancer. The physician can decide on the intervention to address the recurrent cancer based on this scan.

Can you describe what it was like to meet Ken Cornell?

I have been involved from the beginning meeting with the construction company HOK and the architects on the planning of the Cyclotron, Radiotracer Research Lab and the associated Synthetic Organic Chemistry Core Lab for HSRB2. Ronald Crowe, BCNP, the CSI-C Radiopharmacy Manager has similarly been involved in the planning of the Cyclotron and the Radiopharmacy Core facility. At one of the early meetings at the HOK trailer headquarters on campus I found out that Ken Cornell, site construction manager, had received Axumin aka Fluciclovine aka FACBC (the abbreviation I gave the radiopharmaceutical at the time I invented it) to help manage the treatment of his prostate cancer. It gave me great satisfaction and gratitude to meet someone who is involved in the construction of Emory’s new state of the art radiopharmaceutical imaging core facility at HSRB2 who also benefited from this Emory drug discovery. Mr. Cornell is a true gentleman and was sincerely appreciative of our contribution to his medical care. Mr. Cornell isn’t the only acquaintance of mine who has benefited from an Axumin PET-CT scan. A close friend and retired Chemistry Professor at UT-Knoxville, TN and a friend in Roswell, GA have had Axumin PET-CT scans as part of their prostate cancer treatment planning.

What is it like to be involved in the construction project with Ken and Ron?

It has been a wonderful experience to be involved in the project with Ken and Ron. I have been working with Ron Crowe for 20+ years. We have collaborated on the Bench to Bedside translation of 6 radiopharmaceuticals. However, Axumin which is an FDA drug has had the greatest impact on the care of patients.

What are the next steps in FACBC research?

Right now, the FDA has approved FACBC for recurrent prostate cancer. The next step would be to have it approved for adult and children brain cancer and for suspicious aggressive primary prostate cancer before you take out the prostate to see whether or not the cancer is present in the prostate and proximal and distant lymph nodes. Work is ongoing to get additional evidence to see if it has a role in the diagnosis of certain kinds of breast cancers that are not currently diagnosed by imaging agents.

What have you found to be the most rewarding thing about your work?

The most rewarding thing is seeing the work of my team get the return of investment of time, intellectual effort, and funding to come up with a product that is helping give people with cancers a better quality of life in an effort to find a cure.

What advice would you give to your younger self?

A piece of advice that I would give to my younger self is to never doubt yourself, never let anyone talk you out of an idea that you have a commitment to and believe in. If you are given a project and you say you have a solution or idea for that project, never let anyone talk you out of it and say you can’t do it. If you reach for the stars you may end up on the moon.

To learn more about prostate cancer click the links below:
American Cancer Center: https://www.cancer.org/cancer/prostate-cancer/about.html
Centers for Disease Control and Prevention: https://www.cdc.gov/cancer/prostate/index.htm