Duncan Hunter, now a professor emeritus in Western University’s Department of Chemistry, easily recalls the day in the late 1980s that he and his laboratory team were batting around ideas for improving the performance of a radioactive compound used to treat cancerous tumours in the adrenal glands. And he will never forget the day this past summer that one of those ideas became part of a practical clinical treatment, fully approved by the US Federal Drug Administration (FDA). As for decades in between, they tell a story about just how much perseverance it takes to turn a chemical innovation into something doctors can use to help their patients.

Adrenal cancer is rare, limited to only a few hundred people in the United States and Canada every year. The condition, which can lead to high blood pressure and other cardiovascular problems, has been difficult to address, since it does not lend itself to either surgical or chemotherapy. Among the most effective prospects was a radiopharmaceutical called metaiodobenzylguanidine (MIBG), an agent that will travel to the adrenal tissue once it is injected into the body. The drug serves as a delivery vehicle for iodine-131, an isotope that is a beta emitter, producing only low energy electrons that will travel no more than about a millimetre within the confines of the body. If they are close enough to a tumour, however, these particles will break it down.

The problem, which Hunter and his team were considering some 30 years ago, is how iodine-131 is incorporated in MIBG. The standard production method was nucleophilic, which yielded just one in 10,000 drug molecules containing an isotope, a ratio that drastically limited MIBG’s clinical effectiveness.

“It has high chemical purity but low isotopic purity,” Hunter explains.

He and his students adopted an alternative strategy with electrophilic iodine, which could introduce iodine-131 to the MIBG as it was forming.

“The idea is that the MIBG precursor is attached to an insoluble resin,” he says. “Now you treat it with the radioactive iodine. The only stuff that’s released carries the radioactive iodine. All of the rest remains insoluble, so all you have to do is filter it. It will be chemically pure and isotopically pure. Essentially every molecule now carries radioactive iodine.”

Refining the resin to meet this goal took Hunter and his colleagues about 10 years, a scientific accomplishment they demonstrated at the level of micro-Curies of radiation. They knew that it would take the very different expertise found in a pharmaceutical manufacturer to scale up this method of production to the point where it could supply clinical trials and ultimately make its way to sanctioned use in patients.

The university set up a licensing arrangement, which was subsequently taken up by Molecular Insight Pharmaceuticals (née Biostream), a small start-up company based in Massachusetts.

“There weren’t a lot of companies making radiopharmaceuticals,” recalls Hunter, who adds that the challenge of getting the drug to market was exacerbated by the very limited size of the patient population who would benefit.

Besides successfully completing scale-up, Molecular Insight made considerable progress towards FDA approval.  The drug, which became known as Azedra, was fast-tracked and accepted into the FDA’s orphan drug program, which facilitates the approval process for such medicines with limited market reach. They were about half-way through clinical trials when the company ran into financial trouble and the license for Azedra was acquired by Progenics Pharmaceuticals, in 2013.

Following a positive round of clinical trials, Azedra became the FDA’s first approved treatment for adrenal tumours on July 30.  Progenics is in the process of commercializing Azedra.

“Many patients with these ultra-rare cancers can be treated with surgery or local therapies, but there are no effective systemic treatments for patients who experience tumour-related symptoms such as high blood pressure,” says Richard Pazdur of the FDA’s Oncology Center of Excellence in an official statement. “Patients will now have an approved therapy that has been shown to decrease the need for blood pressure medication and reduce tumour size in some patients.”

As for Hunter, he is pleased to see his research resulting in clinical applications, even if it taught him about just how long it can take to enjoy such success.

“If patience is a virtue, then I’m incredibly virtuous,” he told Western’s administration newspaper.