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More bang for your becquerel:
Improving the therapeutic index with novel radiopharmaceuticals


First generation radiopharmaceutical therapies are effective in treating prostate cancer1.  More radiation delivered to cancer cells leads to greater cancer cell death2.  The limitation is the amount of radiation to healthy tissue3.  Blue Earth Therapeutics is committed to the design and development of radioligand therapies that deliver greater dose to tumors while sparing healthy tissue.


  1. Sartor et al, New England Journal of Medicine 2021, DOI: 10.1056/NEJMoa2107322 last accessed on 4 September 2023 
  2. Kalbasi et al; JAMA Oncol. 2015;1(7):897-9063 
  3. Klaus et al; Radiation Oncology 2021, last accessed on 4 September 2023


How does targeted radiopharmaceutical therapy work?

Prostate Cells

How do the different radioisotopes work?

Targeted radiopharmaceutical therapies typically deliver either alpha or beta emitting radioisotopes to the cancer.  Beta radiation causes single strand breaks in DNA across a range of several millimeters of tissue, while alpha radiation causes double strand breaks in DNA across a much shorter range, only a few microns of cells as seen below. 

Both Ranges Final High-Res (1)

Optimisation of the targeting molecule

Blue Earth Therapeutics is using the prostate specific membrane antigen (PSMA) radioligand in the targeting molecule to bind to prostate cancer cells. 

Compound v1.9

Structure of the radio hybrid molecules, 177Lu-rhPSMA-10.1 and 225Ac-rhPSMA-10.1.  

The PSMA ligand (purple), is common to agents in this class, as is the chelator (green).  Differences to other agents are in the linker domain, with the inclusion of a carboxylic acid side chain (circled) and a SiFa group (yellow).  These differences enable an altered biodistribution profile to other agents.1

Blue Earth Therapeutics’ radiohybrid PSMA-targeted radiopharmaceuticals were designed expressly to optimize biodistribution and clearance.  The aims2 were to:

  1. Increase affinity to PSMA-expressing cells
  2. Optimize albumin binding
  3. Optimize overall charge
  4. Increase internalization and retention


  1. Foxton C et al, Journal of Nuclear Medicine June 2022, 63 (supplement 2) 2567
  2. Blue Earth Therapeutics, data on file courtesy of Technical University of Munich

PP-UK-0666 / October 2023