How tiny particles can have a huge impact on liver tumors

This is a guest blog by Frank Nijsen (CSO of Quirem Medical)

The toolbox of an oncologists who is faced with treating liver cancer, is still limited. Fortunately, a new tool will be added shortly to target advanced unresectable liver tumours: microscopic beads loaded with the radioactive isotope holmium-166. These so-called microspheres are brought onto the market by Quirem Medical (Deventer, the Netherlands) as QuiremSpheres®. Recently, QuiremSpheres® was named a top 5 Dutch medical technology innovation.

QuiremSpheres® consists of millions of tiny microspheres. In fact, the microspheres are smaller than a third of the diameter of human hair. Nevertheless, their impact on liver tumors can be huge. The mode of action is twofold:
1) once introduced in the bloodstream to the liver tumours, the microspheres block the hair vessels supplying oxygen and nutrients to the tumours (embolization) and
2) beta-radiation, emitted by the radioactive holmium-166, kills tumour cells from close range (radiotherapy).

It is because of this dual action that the treatment is called radioembolization. Various clinical studies have shown the efficacy of radioembolization for treatment of liver tumors while patients only suffer relatively mild side-effects.

What makes QuiremSpheres® so unique?

QuiremSpheres® microspheres are based on more than 20 years of research and development at the University Medical Center in Utrecht (UMCU), the Netherlands. 15 years ago, radioembolization was already an existing, but largely unknown, treatment method for liver cancer. The researchers at the UMC Utrecht wanted not only to promote the usage of radioembolization, but also develop a new type of microsphere with unique imaging advantages. And they succeeded. The microspheres that were developed cannot only be imaged with SPECT imaging, but also with MRI. By means of these imaging possibilities, the treating clinician can follow the microspheres after they have been injected in the liver artery and assure that the microspheres actually reach the tumours. In addition, Quirem Medical provides proprietary software to precisely calculated the dose that was delivered to the tumour and to the healthy liver tissue.

Manufacturing QuiremSpheres®

The microspheres are synthesised at the production site of Quirem Medical in the Netherlands. During synthesis, holmium-165 chloride is converted into holmium-165 acetyl acetonate crystals, which are mixed with polylactic acid in a solvent. This solution is combined with an aqueous solution, after which microspheres with a size of approx. 30 microns are being formed. The solvent has to be evaporated, and Bronkhorst mass flow controllers deliver the nitrogen flow to enhance and control the solvent evaporation. After washing, sieving and drying, the batch of holmium-165 loaded microspheres is ready. The total synthesis takes almost two weeks.

From raw material to end product

After the production of the ‘cold’ holmium-165 microspheres, a vial containing 33 million microspheres is activated by neutron bombardment in a nuclear reactor. The resulting active holmium-166 microspheres are then transported to a hospital for implantation into the patient. The limited half-life of holmium 166 (26.8 hours) means that good reactor-to-hospital logistics is of key importance.

A few company facts...

Quirem Medical BV is a spin-off from the University Medical Center Utrecht (UMC Utrecht) in the Netherlands. The CEO of Quirem Medical, Jan Sigger, has held numerous senior management roles in the (petro)chemical and medical devices industry. Frank Nijsen, CSO of Quirem and associated professor at the UMCU, has already more than 15 years of experience in the (clinical) research and development of holmium microspheres. In April 2015, Quirem has acquired CE-marking for QuiremSpheres®. Recently, Quirem Medical entered into a strategic alliance with Terumo, a major Japanese medical devices company.