Prof. Marnix G.E.H. Lam
Speaker bio
Currently, three different types of radioactive microspheres are commercially available: yttrium-90 (90Y) resin (SIR-Spheres®, SIRTeX), 90Y glass (TheraSphere®, Boston Scientific) and holmium-166 (166Ho) microspheres (Quiremspheres®, Terumo)(1).
The characteristics of these three types of microspheres are listed in Table 1.
| Characteristic | 90Y resin | 90Y glass | 166Ho |
|---|---|---|---|
| Half-life (h) | 64.1 | 64.1 | 26.8 |
| Type of radiation | β | β | β,γ |
| Decay product | Zirconium-90 | Zirconium-90 | Erbium-166 |
| Diameter (µm) | 32.5 ± 2.5 | 25 ± 10 | 30 ± 15 |
| Density (g/mL) | 1.6 | 3.3 | 1.4 |
| Typical activity / microsphere (Bq) | 40-70 * | 2500 ** | 250-400 |
| Typical number per dose | 30-50 million | 3-5 million ** | 20 million |
*Within FlexDose program activity/microsphere is higher; ** Depending on day post-calibration
The most apparent differences between the three types of microspheres are the type of radiation they emit and their specific activity. 166Ho emits γ-radiation, which allows it to be visualized by SPECT/CT. It is also paramagnetic, so it can be visualized by MRI as well. On the contrary, imaging of 90Y is possible by using either bremsstrahlung-SPECT/CT or PET/CT.
The differences in specific activity are significant: typically low for 90Y resin and high for 90Y glass, with 166Ho having a specific activity in between. This has many consequences: first, the difference in specific activity is translated into the number of particles injected, leading to a larger embolic effect (and potential stasis) for 90Y resin and 166Ho than for 90Y glass. Also, the tolerability of the liver is different for the three types of microspheres, leading to a difference in safety thresholds. A higher number of microspheres leads to a higher number of targeted liver clusters (i.e. healthy liver parenchyma) and a more homogeneous distribution in the liver. [2] With 90Y glass microspheres, there generally is a more heterogeneous distribution of the microspheres, leading to a greater tolerability at high absorbed doses to the healthy liver. This explains why the thresholds for safety are different for the three types of microspheres. Likewise, a more homogeneous distribution, as obtained with 90Y resin and 166Ho, most likely also requires lower tumour absorbed doses to be equally effective. This is indeed reflected in the thresholds found in the literature. [1]
Dose thresholds depend on the microsphere type, but also on the tumour type. Hepatocellular carcinomas are generally hypervascular, and will receive a high tumour absorbed dose, whereas colorectal carcinoma metastases are generally more hypovascular, resulting in a lower tumour absorbed dose and higher absorbed dose in the healthy liver tissue. In any patient, TARE should therefore be performed by using a personalized treatment plan based on a sufficient tumour absorbed dose and safe healthy liver absorbed dose.
This is especially true when treating with a combination of systemic treatment and TARE. Based on multiple RCTs in colorectal carcinoma in the first line setting (SIRFLOX, FOXFIRE and FOXFIRE-Global studies), the combination of first line chemotherapy and TARE cannot be recommended at this time. However, even without using a personalized treatment plan (i.e. a one-size-fits-all approach was used, which likely lead to underdosing of most patients), a statistically significant difference in cumulative incidence of first progression in the liver was still found. [3] EPOCH confirmed this positive signal in the second line setting with a significant improvement not only in hepatic PFS, but also in overall PFS. [4] Similarly, no overall survival benefit could be established in the SORAMIC study when combining sorafenib with TARE in HCC. [5] But, with an individualized treatment plan in the DOSISPHERE-01 study, a very clear anti-tumour effect was found in HCC. [6] Most ongoing studies therefore include personalized treatment as a basis for state-of-the-art TARE.
State-of-the-art TARE, also including high-quality pre-, peri- and post-procedural imaging guidance, paves the way towards new treatment scenarios and new indications in and outside the liver.
Marnix G.E.H. Lam
University Medical Center Utrecht, Utrecht/NL
Prof. Dr. Lam is a Professor of Nuclear Medicine and the Chief of Nuclear Medicine at the University Medical Center Utrecht, Department of Radiology and Nuclear Medicine. He is trained as a nuclear medicine physician and radiologist. He has been a staff member of the Department of Radiology and Nuclear Medicine at the UMC Utrecht since 2007. During his ‘Dutch Cancer Society (KWF)’ research fellowship on translational and clinical research (2010 – 2014), he completed a 2-year research fellowship at Stanford University. In 2013, he was appointed chief of nuclear medicine, and in 2016 he was appointed professor of nuclear medicine. Translational research in molecular medicine has been the scope of Prof. Lam's scientific work, with a special focus on oncology. His aim is to bring new radiopharmaceuticals to clinical practice. This specifically resulted in the introduction of new oncological treatment modalities in the Netherlands, such as bone seeking radiopharmaceuticals for the palliation of metastatic bone pain (153Sm-EDTMP, 188Re-HEDP, 223Ra-chloride), protein-receptor radionuclide therapy (177Lu-PSMA, 177Lu-HA-dotatate), and radioembolization for treatment of hepatic malignancies (90Y microspheres and 166Ho microspheres). Prof. Lam's current research focusses on dosimetry of therapeutic radiopharmaceuticals, image-guided treatment technology, alfa- and beta-emitting isotopes for therapeutic purposes, intra-arterial and intra-tumor treatment approaches, and radio-immunotherapy.
