Professor Jason Lewis: the rise of radiopharmaceuticals

As a global leader in radiochemistry and molecular imaging, Professor Jason Lewis, Deputy Director of the Sloan Kettering Institute in New York City, is well positioned to comment on the dramatic rise of radiopharmaceuticals over the last decade.

His research focuses on the development of radiopharmaceuticals for targeted diagnosis and treatment of cancer.

As a member of the Scientific Advisory Board for the ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals (AMTAR) – housed at AIBN – Professor Lewis supports collaborative efforts in advancing personalised radiopharmaceuticals.

AMTAR’s unique model brings together industry, government and academia, creating a national capability that enables the development, manufacture and translation of targeted radiopharmaceuticals.

During his recent visit, we spoke with Professor Lewis about his research, radiopharmaceuticals and theranostics and the role of industry-academia partnerships in getting cancer treatments to patients.

Firstly, what are radiopharmaceuticals?

Radiopharmaceuticals are basically radioactive forms of drugs.

They could be a small molecule, a peptide, an antibody, a nanoparticle.

The nature of a radiopharmaceutical is that it serves as a platform to deliver an isotope to the disease that you want to visualise or to treat.

What are theranostics?

The combination of a diagnostic with a therapeutic is termed as a theranostic.

This often is used in the context of radiopharmaceuticals because you can have a radiopharmaceutical for imaging and a radiopharmaceutical for therapy.

“In the last few years interest in radiotheranostics has really taken off.”

This has come off the back of a couple of success stories, including Pluvicto, a drug for prostate cancer which targets PSMA (prostate-specific membrane antigen), specific to prostate cancer cells.

There's a diagnostic component (with either fluorine-18 or gallium-68) which detects whether there's PSMA-positive cancer present, and if there is, the patient is given a lutetium form of the same drug to treat that cancer.

"The therapy isn’t given unless you get a positive image with the diagnostic imaging agent, because if the imaging agent doesn't reach the tumour, the therapeutic one won't either."

Patients very often talk about how their quality of their life is significantly improved with this kind of drug, which you often don't get with other drugs, such as chemotherapy.

The compounds are designed specifically to go to the tumour, so there are less off-target toxicities and the amount of the drug you're given is minuscule, which means a low radiation dose and less side effects.

How is AIBN advancing radiopharmaceuticals?

AIBN is in a unique position to help the advancement of radiopharmaceuticals.

All the resources are here. It not only has the radiochemistry, the cyclotron, the preclinical imaging, but the ability to develop new delivery platforms, create new biologics that can carry those isotopes to the disease.

AIBN also has the connections to clinic to get radiopharmaceuticals translated.

“Very few centres globally have that access to that complete spectrum of needs in order to take a drug from the bench into patients.”

What is the potential for personalised medicine?

“One of the big advantages of radiopharmaceuticals, is that we can personalise treatments for a patient.”

And I really hope that the deployment of radiopharmaceuticals in a safe and effective way will lead to an overall improvement in outcomes for our patients.

Using radiotheranostics, we only treat a patient if the imaging agent shows positivity in the tumours, so that itself personalises whether a patient gets a specific treatment, rather than relying on a biopsy.

Biopsies are less accurate than radiotheranostics because they consist of a heterogeneous sample of tissue, whereas imaging agents give a fuller picture of a patient’s tumour burden.

How can we help translation to the clinic in Australia?

It is an expensive undertaking to translate radiopharmaceuticals to the clinic, and a leap of faith must be taken.

That often can't be afforded by academia, so industry's involvement in this is key.

Not only financially, but also for the expertise in how to run trials appropriately and safely.

Ideally, the best way is to have industry's involvement from the beginning to help academic sites develop new drugs that ultimately industry can take on into trials and develop further.

Why is industry involvement essential?

When I look back 10, 20 years ago, the amount of industry interest in this field was relatively small.

But since we have had successes with radiopharmaceuticals such as Pluvicto and Lutathera [to treat gastroenteropancreatic neuroendocrine tumours], industry's interest is now an all-time high.

It's important for us to encourage and take advantage of this, because we need these drugs to become more mainstream.

In Australia, we have companies like Telix and Clarity, who are radiopharmaceutical-based and are becoming global companies, expanding access to these drugs and developing them in other countries.

Using industry's involvement to support phase one trials, we can start to test these drugs in newly diagnosed patients.

Currently, radiopharmaceuticals are deployed as a third or fourth line in a patient's treatment, when all other options have been exhausted.

“We need to start using radiopharmaceuticals sooner in patients, not as a last resort.”