PET/CT imaging showing uptake and retention of 86Y-NM600 (imaging agent) in immunocompetent mice bearing prostate tumors. PET imaging data was employed to estimate tumor dosimetry and prescribe an immunomodulatory 90Y-NM600 (therapy agent) injected activity. Image courtesy of R Hernandez et al., University of Wisconsin-Madison, WI.

PET/CT imaging showing uptake and retention of 86Y-NM600 (imaging agent) in immunocompetent mice bearing prostate tumors. PET imaging data was employed to estimate tumor dosimetry and prescribe an immunomodulatory 90Y-NM600 (therapy agent) injected activity. Image courtesy of R Hernandez et al., University of Wisconsin-Madison, WI.

July 15, 2020 — Targeted radionuclide therapy has been found to create a favorable tumor microenvironment in prostate cancer that improves the effectiveness of immunotherapies. The research, presented at the Society of Nuclear Medicine and Molecular Imaging's 2020 Annual Meeting, shows that immunomodulation can be achieved with relatively low radiation dose that does not affect the normal immune system.

Due to a significantly immunosuppressive tumor microenvironment, immunotherapy has had limited success in the treatment of prostate cancer. External beam radiotherapy, which has been shown to remodel the tumor microenvironment of irradiated tumors to make them more immune-susceptible even at low radiation doses, is limited to the localized disease setting.

"Understanding this treatment dynamic, our goal in this study was to demonstrate that systemically delivered targeted radionuclide therapy provides beneficial immunomodulatory effects that may enhance the response of prostate cancer to immunotherapies," said Reinier Hernandez, Ph.D., assistant professor of medical physics and radiology at the University of Wisconsin-Madison in Madison Wisconsin.

In the study, male mice bearing syngeneic prostate tumor allografts were administered 86Y-NM600 and received positron emission tomography/computed tomography (PET/CT) scans at three, 24, 48 and 72 hours after injection. Radiotracer uptake was analyzed in tumors and in healthy tissues, which allowed researchers to estimate the dosimetry for the targeted radionuclide therapy 90Y-NM600.

Groups of mice were administered either a high or low dose of 90Y-NM600, and tumor growth and survival were monitored for 60 days. A separate group of mice received the same 90Y-NM600 doses and were euthanized to analyze the immunological effects (flow cytometry, immunohistochemistry and Luminex cytokine profiling) of the radionuclide therapy on the tumor microenvironment and lymphoid tissues.

Data from PET/CT imaging revealed that 90Y-NM600 immunomodulates the tumor microenvironment of prostate tumors by modifying tumor-infiltrating lymphocyte populations, upregulating checkpoint molecules, and promoting the release of pro-inflammatory cytokines. 90Y-NM600's pro-inflammatory effects on the tumor microenvironment were found to be elicited at relatively low radiation doses without incurring systemic toxicity.

"Our results provide a rationale for combining targeted radionuclide therapy with immunotherapies, which, so far, have proven ineffective in prostate cancer. Improving immunotherapy in prostate cancer could bring about a potentially curative treatment alternative for advanced-stage patients. We are actively working to advance the immunomodulation concept into Phase I clinical trials," stated Hernandez.

The study also presents a paradigm change in targeted radionuclide therapy, where the maximum tolerable dose may not always be the most beneficial to patients. "A key finding of our work is that immunomodulation is best achieved with a relatively low radiation dose to the tumor which does not affect the normal immune system," Hernandez noted. "As high radiation doses to normal lymphoid organs can negate the benefits of immunomodulation, estimating the radiation doses imparted to the tumor and normal tissues prospectively by using patient-specific image-based dosimetry techniques is critical. This means that, essentially, a theranostic approach must be implemented."

Abstract 36. "Low-dose TRT reshapes the microenvironment of prostate tumors to potentiate response to immunotherapy," Reinier Hernandez, Hemanth Potluri, Eduardo Aluicio-Sarduy, Joseph Grudzinski, Christopher Massey, Christopher Zahm, Jonathan Engle, Douglas McNeel and Jamey Weichert, University of Wisconsin-Madison, Madison, Wisconsin. SNMMI's 67th Annual Meeting, July 11-14, 2020.

For more information:

Related SNMMI20 Content:

SNMMI Channel

PSMA PET/CT Can Change Management in Recurrent Prostate Cancer

Total-body Dynamic PET Successfully Detects Metastatic Cancer

New PET Radiotracer Proven Safe in Imaging Malignant Brain Tumors

Targeted Radionuclide Therapy Enhances Prostate Cancer Response to Immunotherapies

New PET/MRI Approach Pinpoints Chronic Pain Location, Alters Management

Related Content

News | Magnetic Resonance Imaging (MRI)

November 28, 2023 — New research being presented this week at the annual meeting of the Radiological Society of North ...

Time November 28, 2023
News | Magnetic Resonance Imaging (MRI)

November 27, 2023 — Stronger quadriceps muscles, relative to the hamstrings, may lower the risk of total knee ...

Time November 27, 2023
News | Quality Assurance (QA)

November 25, 2023 — Mirion announced that it will debut the new Instadose VUE personal dosimeter, from its Dosimetry ...

Time November 25, 2023
News | PET-CT

November 22, 2023 — Siemens Healthineers announces the Food and Drug Administration (FDA) clearance of the Biograph ...

Time November 22, 2023
News | Artificial Intelligence

November 21, 2023 — Heuron, a medical AI (artificial intelligence) imaging software solution company, under the ...

Time November 21, 2023
News | Information Technology

November 21, 2023 — GE HealthCare has received U.S. FDA 510(k) Clearance for the new version of Digital Expert Access ...

Time November 21, 2023
News | PET Imaging

November 8, 2023 — In a small study, researchers at the National Institutes of Health have found that positron emission ...

Time November 08, 2023
Feature | Radiation Oncology | By Melinda Taschetta-Millane

Imaging advancements, including 3D Doppler imaging to detect cancers in numerous organs, are used to accurately guide ...

Time November 03, 2023
Feature | Radiation Oncology | By Christine Book

Howard Sandler, MD, FASTRO, Radiation Oncology Department Chair at Cedars-Sinai Medical Center, took the helm as ...

Time November 03, 2023
News | Linear Accelerators

October 25, 2023 — A new order for several Elekta Harmony linear accelerators (linacs) in Ukraine will complement the ...

Time October 25, 2023
Subscribe Now