Press release of July 14, 2026

A second look to aim better

A research team at HZDR combines PET and SPECT diagnostic approaches to treat advanced prostate cancer

Prostate cancer is one of the most common cancers affecting men worldwide. However, planning personalized radiotherapy in the advanced stages of the disease still requires more precise tools. Researchers at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) have now tested a novel approach. A combination of two diagnostic imaging techniques could pave the way for personalized radiotherapy. The results of the study, funded by the Wilhelm Sander Foundation, have been published in the Journal of Medicinal Chemistry (DOI: 10.1021/acs.jmedchem.6c00161).

When hormonal treatment fails to slow the spread of metastatic prostate cancer, patients often face limited therapy options. One promising method is targeted alpha therapy using the radionuclide Actinium-225. Radioactive molecules are directed specifically towards those cancer cells that express particularly high levels of the surface protein PSMA (prostate-specific membrane antigen), destroying them from within.

For this therapy to work optimally on a given patient, practitioners must first determine how the radioactive drug is distributed within the body and how much of it reaches the cancer cells. Visualizing the radiotherapeutic agent with a PET (Photon Emission Tomography) scan for a few hours – e.g., with Gallium-68 and Fluorine-18 – is often insufficient for reliable dosage planning.

The idea: a pair of molecular twins

The HZDR team therefore pursued a different strategy: The researchers developed compounds that are chemically identical to the therapeutic molecule but can also be labelled with diagnostic radionuclides. This is known as the ‘radiohybrid concept’. Two different radionuclides of different elements are incorporated into the same carrier molecule in a way that alters its pharmacological behavior as little as possible.

Specifically, they used two complementary radionuclides: Lanthanum-133 for high-resolution, 3-D PET imaging, and Iodine-123 for SPECT imaging (single-photon emission computed tomography). Thanks to the longer half-life of Iodine 123 – the time it takes for half of the radionuclide to decay – the imaging can be performed up to 44 hours after injection. This is particularly useful in therapeutic approaches involving long-lived alpha emitters. Both radionuclides are produced at HZDR’s own cyclotron, a compact circular accelerator. Iodine-123 is produced in collaboration with ROTOP Pharmaka GmbH.

“For the first time, our radiohybrid approach allows us to label one and the same molecule with two different diagnostic radionuclides and observe its behavior in the body over the long term without altering the molecule itself in any way,” summarizes the study’s lead researcher, Dr. Constantin Mamat from the HZDR Institute of Radiopharmaceutical Cancer Research.

Identical tumor uptake, surprisingly different blood kinetics

The utilized carrier molecules consist of three units: a PSMA-binding entity, a cage-like chelator called ‘Macropa’ to securely encapsulate the radiometal, and an albumin binder to temporarily anchor the molecule to the protein albumin in the bloodstream, prolonging its half-life. The team developed a single-arm and a double-arm variant, which is able to bind two PSMA molecules to the tumor cell surface simultaneously.

In cell culture experiments with human prostate cancer cells, all compounds reliably recognized the tumor marker PSMA. Up to 97 per cent of the bound molecules were taken up into the cells within 60 minutes. In tumor-bearing mice, tumor uptake was virtually identical, regardless of whether the compound was labelled with Lanthanum-133 or Iodine-123. Both sets of experimental results provide key evidence to support the radiohybrid approach. Surprisingly, however, the iodine-labelled compounds remained in the bloodstream slightly longer than their chemically identical counterparts that were labelled with Lanthanum-133. Despite extensive analysis, the exact cause of this phenomenon remains unclear.

“This observation shows that even chemically identical molecules can possess different pharmacological properties simply due to the position of the radionuclide,” explains Dr. Martin Ullrich, co-author of the study. “This underlines the importance of testing both diagnostic strategies thoroughly before conclusions can be drawn for individual therapeutic dose planning.”

Towards personalized cancer medicine

Despite the unresolved issue of the blood half-life, the results of the cell and mouse experiments show that overall, the radiohybrid approach works: The diagnostic molecule reliably visualizes the tumor uptake of the therapeutic agent. For the first time, this concept has been systematically tested using Iodine-123 and Actinium-225, supplemented by Lanthanum-133 as a PET radionuclide for seamless imaging, from tumor uptake all the way to excretion via the kidneys.

This opens up new possibilities for patients: When doctors know exactly how the therapeutic agent is distributed within the body and how long it remains in which part of the body, the optimal radiation dose can be calculated for each individual – high enough to target the tumor, yet low enough to spare health tissue. The Dresden research team plans to gradually advance the most promising compound towards clinical trials.

Publication:

T. Krönke, M. Ullrich, M. K. Blei, K. Zarschler, J. Schädlich, S. A. Brühlmann, K. Kopka, J. Pietzsch, S. Stadlbauer, C. Mamat: Diagnostic Twins: Exploring the Radiohybrid Concept with Iodine-123 and Lanthanum-133 for PSMA-Targeted SPECT and PET Imaging, in Journal of Medicinal Chemistry, 2026. (DOI: 10.1021/acs.jmedchem.6c00161)

Further information:

Dr. Constantin Mamat | Dr. Martin Ullrich
Institute of Radiopharmaceutical Cancer Research at HZDR
Tel.: +49 351 260 2805 | +49 351 260 3989
Email: c.mamat@hzdr.de | m.ullrich@hzdr.de

Media contact:

Simon Schmitt | Head
Communications and Media Relations at HZDR
Phone: +49 351 260 3400 | Mobile: +49 175 874 2865 | Email: s.schmitt@hzdr.de