Clinical Center News
Fall 2019

Clinical trial with alpha particle radiation treatment attempts to target and destroy cancer cells

Patient standing with care providers
On July 23, Keith Grant (second from right), from Maryland, was the first patient in the United States to receive radioisotope Thorium-227 in treatment for mesothelioma. Grant will return every six weeks to the NIH Clinical Center for therapy. Grant stands with his care team, Maria Agra, a research nurse for Frederick National Laboratory, Dr. Frank Lin, chief of the Targeted Radionuclide Therapy Section at NCI, and Dr. Raffit Hassan, chief of the Thoracic and GI Malignancies Branch and head or the Thoracic Oncology Section at NCI.
 

On July 23, researchers in the NIH Clinical Center treated the first patient in the U.S. with radioisotope Thorium-227 for mesothelioma. The clinical trial uses Thorium-227 to target and attack a protein called mesothelin, which is highly expressed in many cancers.

Thorium-227 is an unstable radio-isotope that emits an alpha particle upon undergoing radioactive decay, explained Dr. Frank Lin, Chief of the Targeted Radionuclide Therapy Section at the National Cancer Institute (NCI). According to Lin, who is the clinical authorized user for the radioactive administration of the thorium at the NIH Clinical Center, most current forms of systemic radiation therapy using radionuclides emits radiation particles that are very small such as beta particles. But, the higher the mass or energy of the emitted particle, the more tumor damage can be done. Alpha particles, such as Thorium-227, are several thousand times larger than beta particles. Before now, alpha emitters have never been used to treat patients at NIH.

The new drug being tested (BAY 2287411) is made up of two components that are combined into one molecule. First is an antibody that allows the drug to locate and target the mesothelin protein on the cancer cells. Second is the Thorium-227, which is the "active ingredient" of the combined molecule. This is akin to having a smart bomb against cancer cells, where the antibody provides the targeting system, and the Thorium-227 is the radioactive payload. Once bound to tumor cells, the thorium undergoes its natural radioactive decay and exposes tumor cells to lethal doses of alpha radiation.

"Our goal is to demonstrate the safety and tolerability of this drug and to get preliminary evidence of anti-tumor efficacy," said the study's principal investigator, Dr. Raffit Hassan, the Chief of the Thoracic and GI Malignancies Branch and Head or the Thoracic Oncology Section at NCI. "This is a treatment for patients with mesothelioma and ovarian cancer who have failed standard therapies and provides a new treatment approach for treating their cancer."

For more than two decades, Hassan and colleagues have been investigating the protein mesothelin as a target for cancer therapy.

"It feels exciting thanks to the work by Frank and [the NIH Office of Research Services] Division of Radiation Safety. They have been critical in working with the Nuclear Regulatory Commission to allow us to use the Thorium radio-conjugate here. It is a very complicated process, but because of a lot of their work we were able to do it and hopefully this opens the door for Alpha therapies not only for targeting mesothelin but other cancers," Hassan said.

While it may take a number of years to conduct the trial and assess its effectiveness, Hassan said if successful, it could be used on other cancers such as lung cancer and pancreatic cancer.

- Molly Freimuth

Stories
Pharmacy symbol icon
Nurses working on a pedigree diagram within a patient's medical record
nurse kneeling beside a pediatric patient
people gathered around computers
Patient standing with care providers
The metabolic kitchen staff creating precisely measured ultra-processed and unprocessed meals for study participants
Attendees of the Open Notes session gathered together
Pediatric patient ten-year-old JoJo with Dr. Cynthia Tifft
Branden Bolivar proposes to Marissa Amuso, a patient, May 9 at the NIH Clinical Center
Tom Kaminski with Dr. Sherman Souther
Kayden Reinke, at the age of 2, holding Lammie
Project SEARCH graduates and team
Dr. Marijo Bilusic
Singer-songwriter and pianist Chris Urquiaga
Three women photographed with an award
Man in fatigues talking to care provider
A pediatric patient with her mother and members of the NIH Blood Bank
NIH musical group led by Dr. Collins performing on stage
Dr. Eric Betzig at the podium
Children conducting a science experiment
Trina Davis
Graphic of a cochlear implant
Staff member using a sewing machine
Dr. Saul Rosen
a patient's wristband getting scanned upon checking in or out
Michael Bard, a volunteer medical musician, holds his guitar in a patient room
Nancy Holmfeld
Rare Disease Day logo
People dancing in the atrium
people taking a selfie
Health Information Management Department staff posing for a photo
Young boy holds up a sign that says I love clean hands
FEVS logo
Teresa Bauch showing children cultures of infectious diseases on Take Your Child to Work Day
ePMAP
Staff at the site of a new facility
Woman typing on a Workstation on Wheels computer
Staff view a piece of paper in a kitchen
Men on stage at the awards
Josh and Lisa Danielpour
A redesigned common area in the NIH Clinical Center Edmond J. Safra Family Lodge
Nicholas Rodriquez enjoying the Virtual Reality experience
A young boy voting on gingerbread houses
Retired Navy Capt. Pius A. Aiyelawo speaking at the NIH Veterans Day Celebration Nov. 7
Pediatric patients are given candy by departments at the Clinical Center
a man smiling
Workplace Climate and Harassment Survey. Take the Survey now. Diversity.nih.gov