News | Radiopharmaceuticals and Tracers | April 10, 2024

177Lutetium-labeled radiohybrid Prostate-Specific Membrane Antigen (177Lu-rhPSMA-10.1) is in development as a highly optimized, next generation therapeutic radiopharmaceutical

177Lutetium-labeled radiohybrid Prostate-Specific Membrane Antigen (177Lu-rhPSMA-10.1) is in development as a highly optimized, next generation therapeutic radiopharmaceutical

Getty Images

April 10, 2024 — Blue Earth Therapeutics, a Bracco company and emerging leader in the development of innovative next generation therapeutic radiopharmaceuticals, today announced results from a series of preclinical analyses designed to identify synergistic combinations of known anticancer drugs with 177Lu-rhPSMA-10.1 radioligand therapy, and from a preclinical efficacy analysis of the lead novel drug combination for the treatment of prostate cancer. Results from a systematic in vitro screen identified MEK inhibitor cobimetinib as a lead candidate with potential for synergistic combination with 177Lu-rhPSMA-10.1, and the preclinical efficacy analysis showed enhanced therapeutic effect of this drug combination when compared to the untreated control and to the single agents alone. The data were presented in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego, Calif. 177Lu-rhPSMA-10.1, an investigational radiohybrid (rh) Prostate-Specific Membrane Antigen-targeted therapeutic radiopharmaceutical, is the lead candidate in Blue Earth Therapeutics’ oncology development program of next generation therapeutic radiopharmaceuticals.

“Radioligand therapy targeting PSMA has been shown to be an effective therapy in men with prostate cancer, and we are pleased to share these promising preclinical results from our study of 177Lu-rhPSMA-10.1 drug combinations with the scientific community at the prestigious AACR Annual Meeting 2024,” said David E. Gauden, D.Phil., Chief Executive Officer of Blue Earth Therapeutics. “Combination approaches are of increasing interest among the medical community, as we know tumors are heterogeneous and some prostate cancer cells do not express PSMA. Importantly, these combinations need to avoid overlapping toxicity. Results from this preclinical study presented at AACR demonstrated a synergistic therapeutic effect between 177Lu-rhPSMA-10.1 and an MEK inhibitor. This may be due to inhibition of the MEK-MAPK pathway during DNA damage response, resulting in radiosensitization of cancer cells to 177Lu-rhPSMA-10.1. Our ongoing Phase 1/2 clinical trial (NCT05413850) is evaluating 177Lu-rhPSMA-10.1 radioligand therapy as a monotherapy in treating men with metastatic castrate resistant prostate cancer, and we may look to evaluate this combination in the clinic in the future.”

About the study

More than 150 FDA-approved anticancer drugs were screened in a clonogenic survival assay of 22Rv1 cells using the test drug alone, at a range of concentrations <20 µM to determine the IC50. The results were then compared to incubations of the drug plus 15 MBq/mL 177Lu-rhPSMA-10.1 (2-hour incubation) after 10 days. Five lead candidates were then selected for a focused screen where the impact of 177Lu-rhPSMA-10.1 (0–25 MBq/mL) on the drug IC50 was determined. A synergy score was determined using the zero interaction potency (ZIP) reference model and the multi-dimensional synergy of combinations (MuSyc) platform. Therapeutic efficacy of the lead combination, 177Lu-rhPSMA-10.1 (single 30 MBq iv dose) plus cobimetinib (0.25 mg orally per day for 21 days), was then evaluated in 22Rv1 prostate tumor xenograft models and compared to the single agents alone (n = 8 per group, plus untreated controls). Tumor volume was measured 2 times per week for 69 days. Two-way ANOVA and Tukey’s multiple comparisons test (data analyzed until n = 3 remained per group) and Kaplan-Meier Log-rank survival analyses were performed.


The in vitro screen identified the MEK inhibitor cobimetinib as a lead candidate for synergistic combination with 177Lu-rhPSMA-10.1 across a wide concentration range, with a ZIP synergy score of 13.25% (95% CI ± 2.17) and promising results on MuSyc analysis. The 177Lu-rhPSMA-10.1 plus cobimetinib MEK inhibitor combination significantly suppressed tumor growth in vivo versus untreated controls (from day 13–30; p<0.01) and 177Lu-rhPSMA-10.1 alone (from day 17–30; p<0.001). The median survival in the combination group (49 days) was significantly longer versus the untreated group (23 days; p=0.001) and the group treated with 177Lu-rhPSMA-10.1 alone (36 days; p=0.002).

The results were discussed in a poster presentation, “Evaluation of a synergistic drug combination with 177Lu-rhPSMA-10.1 for prostate cancer: Results of an in vitro screen and in vivo proof of concept study,” by Caroline Foxton, Ph.D., Blue Earth Group, Oxford, UK, at the AACR Annual Meeting 2024 on April 7, 2024. The abstract is available in the online program here .

About Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA)

rhPSMA compounds are referred to as radiohybrid (“rh”), as each molecule possesses three distinct domains. The first consists of a Prostate-Specific Membrane Antigen-targeted receptor ligand which attaches to and is internalized by prostate cancer cells. It is attached to two labelling moieties which may be radiolabeled with diagnostic isotopes such as 18F or 68Ga for PET imaging, or with therapeutic isotopes such as 177Lu or 225Ac for radioligand therapy – enabling the potential for a true theranostic technology. They may play an important role in patient management in the future, and offer the potential for precision medicine for men with prostate cancer. Radiohybrid technology and rhPSMA originated from the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive, worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, and therapeutic rights in 2020, and has sublicensed the therapeutic application to its sister company Blue Earth Therapeutics. Blue Earth Therapeutics and Blue Earth Diagnostics work closely on the development of 177Lu-rhPSMA-10.1. Currently, Blue Earth Therapeutics’ rhPSMA compounds have not received regulatory approval.

For more information:


Related Medical Radioisotopes Content: 

Blue Earth Therapeutics Announces Results of Early Clinical and Preclinical Studies of Investigational 177Lu-rhPSMA-10.1 in Treatment of Prostate Cancer

University of Missouri Research Reactor Helps Supply Critical Medical Isotopes During Global Disruption 

Update on Unplanned Outage of the HFR Reactor 

SNMMI Issues Alert That HFR Outage Will Impact Isotope Supply 

NorthStar Medical Radioisotopes Advances Focus on Therapeutic and Specialized SPECT Radiopharmaceuticals 

How Nuclear Fusion is Revolutionizing Medical Isotope Production 

FDA Approves Additional Molybdenum-99 (Mo-99) Filling Lines at NorthStar Medical Radioisotopes 

Medical Isotope Industry Opposes Export of Highly Enriched Uranium for IRE 

IBA and NorthStar Medical Radioisotopes Expand Collaboration to Enable Global Availability of Tc-99m 

VIDEO: Advances in Radiopharmaceutical Therapy

Related Content

News | ASTRO

May 17, 2024 — Registration opens today for the American Society for Radiation Oncology's (ASTRO) 66th Annual Meeting ...

Time May 17, 2024
News | Radiation Oncology

May 10, 2024 — Mariana Oncology, a fully integrated biotechnology company pioneering a new era of radiopharmaceutical ...

Time May 10, 2024
News | Radiopharmaceuticals and Tracers

May 8, 2024 — Blue Earth Diagnostics, a Bracco company and recognized leader in the development and commercialization of ...

Time May 08, 2024
News | Prostate Cancer

May 2, 2024 — GT Medical Technologies, Inc. (GT MedTech), a medical device company with the mission of improving the ...

Time May 02, 2024
News | Radiation Therapy

May 1, 2024 — Sun Nuclear, a Mirion Medical company, today announced the upcoming version 5.0 release of its SunCHECK ...

Time May 01, 2024
News | Proton Therapy

April 29, 2024 — Koneksa, a healthcare technology company pioneering evidence-based digital biomarkers, announced today ...

Time April 29, 2024
News | Radiopharmaceuticals and Tracers

April 5, 2024 — RLS Radiopharmacies, America’s only Joint Commission-accredited radiopharmacy network, today announced ...

Time April 05, 2024
News | Molecular Imaging

March 29, 2024 — Magnetic resonance imaging (MRI) is a cornerstone in the landscape of medical diagnostics, celebrated ...

Time March 29, 2024
News | Radiopharmaceuticals and Tracers

February 21, 2024 — Blue Earth Therapeutics, a Bracco company and emerging leader in the development of innovative next ...

Time February 21, 2024
News | Radiopharmaceuticals and Tracers

February 14, 2024 — PanTera, the Belgian joint venture created by IBA and SCK CEN to secure large-scale production of ...

Time February 14, 2024
Subscribe Now