Fighting prostate cancer with nuclear medicine

Nuclear medicine uses radioactive agents to detect and treat conditions and, like music, is a great passion in Dr Thabo Lengana’s life.

Halfway through his training as a specialist, the University of Pretoria and Steve Biko Academic Hospital nuclear physician liked nothing more than picking a backing riff on his bass guitar for his band of musician friends.

“We did mostly jazz, but also rhythm and blues. That was when I still had time to relax. Not since this PhD though. Right now, it’s motivating me to finish this research so I can get back to it!” he says when asked about his hobbies.

His musical role as a bassist is a wonderful metaphor for his potentially groundbreaking research into if a specific injectable tracer agent is much more effective in detecting recurring prostate cancer than other methods. According to a study published in the National Academy of Sciences, our brains can find a song’s rhythm more accurately by listening to the low tones played on the bass. While musicians love to joke otherwise, the bassist is the most important member in a band.

Dr Lengana’s “low-tones” in his research are already fine music to the ears of physicians involved in detecting and treating prostate cancer. He hopes to publish the score on how accurate the injectable 18F-prostate-specific-membrane-agent-1007 (PSMA-1007) is during scans.

How the unique injectable tracer works

Doctors use tracers to make masses or certain body parts show up during scans. This can be used to detect and sometimes even treat disease. 18F PSMA 1007 is an injectable tracer agent that travels through the bloodstream that singles out and only locks on to cancerous cells that express prostate-specific membrane antigens. In other words, 18F PSMA 1007 targets cancer in prostate cells.

Dr Lengana is part of a small group of South African nuclear physicians who punch well above their weight globally in the new field of theranostics. Theranostics uses tracer agents to both diagnose and treat a condition.

Dr Lengana is using his PhD enquiry, backed by a Discovery Academic Fellowship, to study patients with prostate cancer whose levels of prostate-specific antigen (PSA) go up again after surgery or radiation. This is called ‘biochemical reoccurrence’ of prostate cancer. A high level of prostate-specific antigen can mean that someone has prostrate cancer.

While there are other PSMA tracers, their limitation is that they are excreted mainly via the kidney into the bladder. Agent 1007 is mainly cleared out by the liver into the gall bladder. This means 18F PSMA 1007 does not add tracer elements to the bladder that makes it difficult for the doctor to see the pelvic floor fully during a scan.

Dr Lengana explains that about one third of prostate cancer patients will have a recurrence of the disease if the pelvic floor is obscured.

Multiple benefits of global theranostic approach

With recurring prostate cancer, patients often have a surgical scar called ‘fibrosis’ from the radiation treatment. This means the dead and fibrotic tissue can make it difficult to see and identify active disease during a standard MRI or CT scan.

By locking only onto cancer cells, 18F PSMA 1007 sidesteps this problem too and eliminates any confusion between cancerous cells and fibrotic or dead tissue. Dr Lengana says this involves a whole-body scan with positron-emission tomography (PET-scan), a nuclear medicine imaging technique used to observe metabolic processes in the body.

This allows doctors to more accurately identify cancerous sites and makes precise radiation possible. “We can see where it’s hiding, whereas other scans and agents can miss it – it’s a very real, unmet diagnostic need,” he adds.

He hopes that the findings of his research will demonstrate an increased sensitivity and lesion detection of prostate cancer cells at low prostate-specific antigen (PSA) values that will result in 18F PSMA 1007 replacing MRI and CT scans as the imaging standard in patients with recurrent cancer.

The audience applause, however, is reserved for the therapeutic version of PSMA. This destroys the cell DNA of the cancer cells. “So, we first identify the site of the cancer with the tracer 18F-PSMA-1007. Then, we inject a therapeutic version of the PSMA tracer, which locks onto the PSMA-expressing prostate cancer sites and gives off radiation that kills the cancerous cells while bypassing normal tissue that does not express PSMA,” he explains.

He says this theranostic approach has been available globally for about five years and his scientific team has had access to it for about the same length of time. By mid-May 2019 they had reached their data analysis phase. If all goes to plan, they’ll be publishing by mid-2021. “Overall, we’re hoping that outcomes will be much better,” he adds.

Nowhere to hide for cancer cells

Asked to sketch the best-case scenario, Dr Lengana says that at individual patient management level, identifying cancer recurrence earlier would increase the chances of a procedure curing the cancer and thus improve survival rates.

Identifying sites of recurrence early would give the treating doctor an opportunity to direct therapy to the specific site where cancer spread, and avoid additional procedures and their complications. This could have a significantly impact on a population level.

So far, preliminary findings show that they are locating cancer sites missed by other imaging techniques. His team has also detected other cancers hiding elsewhere in a patient's body. “Overall, we're hoping that outcomes will be much better,” he says.

Back to the music

Asked what led him to medicine and research, Dr Lengana says he can’t single out an event, but remembers being around his father’s doctor friends and thinking: “This will be a great thing to do.” He wonders if the influence could be subconscious because as an infant, he was sickly and often in and out of hospital.

As a middle child whose father worked for a global petroleum company and whose mother took care of them at home, Dr Lengana says his parents “did the best they could with what they had”.

He’s married to a doctor working in healthcare risk management, and they have a young daughter. His bass guitar case remains clipped shut for now. Yet, like his research, he can feel its promise and cannot wait to get back to it, laying down those fundamental bass notes again.