Dual isotope radionuclide therapy appears to be feasible and effective for treating colorectal cancer, according to research presented at the 2024 Society of Nuclear Medicine and Molecular Imaging (SNMMI) meeting in Toronto.
In fact, this combined approach may translate to reduced risk of treatment-related side effects, according to a team led by Sara Rinne, PhD, of Weill Cornell Medicine in New York.
"The ability to simultaneously deliver different radioisotopes with complementary radiobiological properties creates new opportunities for improving therapy outcomes and improving patient care," Rinne said in a statement released by the SNMMI.
Targeted radionuclide therapy has been shown to be successful in treating cancer, yet some patients do not respond to the chosen protocol and others experience relapse or develop treatment resistance, Rinne and colleagues explained. That's why mingling two radionuclides could be an effective solution.
Autoradiography images of GPA33(+) SW1222 xenograft sections acquired using an ionizing-radiation quantum imaging detector (iQID) camera. The images effectively illustrate that the DOTA-PRIT (DOTA pretargeted radioimmunotherapy) approach can be used to simultaneously deliver Ac-225 and Lu-177 to tumors. Mice were injected with Lu-177 or Ac-225 radioligand alone (first and second row, respectively), or a Lu-177/Ac-225 mixture (row 3 and 4), after pretargeting with anti-GPA33/anti-DOTA bispecific antibody. First column shows the combined signal (Lu-177 and Ac-225 together), second column (⍺-counts) shows uptake of Ac-225, and third column (β-counts) show Lu-177uptake. Fourth column shows an overlay of the Ac-225 signal (red) and Lu-177 signal (green). Image and caption courtesy of SNMMI.
"The use of both alpha- and beta-emitting nuclides could better address tumor heterogeneity due to their varied penetration depths and ability to induce different radiobiological effects, thus creating more complex damage to the tumor and offering a potentially successful treatment approach for a larger patient population," Rinne said.
The investigators conducted a study that assessed the feasibility and therapeutic efficacy of combined lutetium-177 (Lu-177)/actinium-225 (Ac-225) pretargeted radioimmunotherapy compared with separate, single therapies of Lu-177 or Ac-225 in mice with human colorectal cancer xenografts. They found that the combined treatment was equally as effective as single radionuclide protocols for shrinking tumors.
"Overall, pretargeted dual-isotope therapy has the potential to be a versatile approach to help a larger patient population and overcome existing barriers to successful targeted radionuclide therapy," Rinne said.
