Are holmium microspheres a next generation embolic for radioembolization?

16
New horizons
November 2014
Are holmium microspheres a next
generation embolic for radioembolization?
The CIRSE 2014 Excellence and Innovation Award was presented to the
University Medical Centre of Utrecht team in The Netherlands where radioactive
holmium-166 microspheres were developed. A spin-off company, Quirem
Medical, seeks to commercially introduce these as QuiremSpheres in early
2015 for the treatment of liver cancer patients worldwide. Interventional News
finds out more…
T
he team in Utrecht is led
by Maurice van den Bosch
(professor and head of
Radiology), Marnix Lam (head of
Nuclear Medicine), and associate
professor Frank Nijsen, who is the
inventor and project leader of the
valorisation of the microspheres.
What has your early
research on radioactive
holmium-166
poly L-lactic acid
microspheres (Ho-166)
shown?
These microspheres were
developed as an alternative to
yttrium-90 (Y-90)-microspheres.
Besides the high-energy betaradiation required for tumour destruction, these microspheres also
emit low-energy gamma radiation,
which can be used for quantitative
SPECT imaging. Furthermore, the
paramagnetic property of holmium
allows for high-resolution MRI to
be performed. The particles have
been intensively tested for their
stability, performance and imaging
possibilities. Their biocompatibility and safety have been explored in
laboratory animals and in a phase
I clinical study in 15 patients, the
results of which were published in
Lancet Oncology. We have learned
that Ho-166 radioembolisation is
feasible and safe for the treatment
of patients with unresectable and
chemorefractory liver metastases and enables image-guided
treatment. This year, the phase II
efficacy study in patients with liver
malignancies will be completed
and two new studies are now
open for recruitment. Presently, in
vivo imaging and image-guided
delivery of these holmium-loaded
microspheres constitute the main
points of our pre-clinical research.
In the near future, these holmium
microspheres will be able to be
administered under real-time MRI.
For the physician to see what he
treats and to treat what he sees, it is
imperative that he knows the precise doses and the exact distribution of the holmium particles, both
in the liver and in the tumours,
using either quantitative MRI or
gamma scintigraphy.
What potential
advantages does
radioembolization
with Ho-166 offer over
radioembolization with
Y-90?
Compared to the current radi-
oembolization treatment using
Y-90, the application of Ho-166
microspheres in the treatment
of liver cancer brings several
important benefits. Despite the
efficacy of Y-90, the current
radioembolization technique poses
several shortcomings. One major
disadvantage of radioembolization
with Y-90 microspheres is that the
microspheres are currently poorly
visualised with medical imaging
techniques. This hampers a good
understanding of the relationship between dose and response
of the tumour. Furthermore, the
biodistribution during and after
treatment cannot be observed in
detail. Consequently, this can result in unsuccessful or suboptimal
treatment.
Similar to Y-90, holmium
microspheres emit high-energy ßradiation that eradicates tumours.
But, unlike Y-90, Ho-166 has the
following benefits:
„„ It also emits γ-radiation. Gamma emission allows quantitative
nuclear imaging and dosimetry,
thereby preventing the over- and
under-dosing. Moreover, it opens
the possibility to monitor the
patient during the treatment allowing the physician to adjust the
Figure 1
L to R: Remmert de Roos, Marnix Lam, Jip Prince, Lenny Verkooijen,
Frank Nijsen, Andor van den Hoven and Maurice van den Bosch
treatment on-site to ensure that all
tumours receive an optimal dose;
„„ Holmium is a paramagnetic
element too, which allows visualisation with high resolution MRI.
The application of this holmiumbased approach will thus revolutionise the treatment of cancer in
all stages of the treatment: pretreatment planning and dosimetry;
real-time monitoring during the
actual treatment and monitoring
efficacy after the treatment.
Monitoring of the distribution
enables interventionists to verify
if lethal doses reach all cancer
lesions in the liver. It enables the
physician to adapt and optimise
the treatment plan during the procedure and tailor it to the personal
needs of the patient. To illustrate,
figure 1 shows a patient’s liver
with two metastatic tumours
(tumour 1 and tumour 2). Tumour
1 is hit with the treatment dose (as
shown by the holmium lighting
up white for nuclear imaging and
red for MRI) and will succumb
to the radiation. However, the
particles did not reach tumour 2.
If left unseen (and untreated) this
tumour will therefore keep growing and lead to patient mortality.
Thus, the ability to visualise
Ho-166 can improve treatment
efficacy. s
First, an assessment of the
required dose must be made in
the pre-treatment stage. As Y-90
cannot be detected using Single
Photon Emission Computed Tomography (SPECT), a scout-dose
of technetium is used instead.
Unfortunately, the predictive
value of technetium for Y-90 is
known to be poor. In contrast
Ho-166 can be detected using
SPECT providing a major asset
in dosimetry. Secondly, Ho-166
microspheres can be imaged by
MRI after the treatment, resulting
in high resolution maps of the
microsphere distribution in the
liver which gives powerful insight
in the dose distribution to the tumours. This information is needed
to decide on further treatment and
thereby improve patient outcome.
Finally, the half-life of holmium is
shorter than that of yttrium (26.8
hours versus 64 hours). The short
half-life of the holmium isotope
means that the logistics need to
be professionally organised to
meet customer demand. However,
the timely delivery of medical
isotopes with a short half-life is
already daily business for a large
number of specialised transport
companies.
First dedicated UK support website for
patients treated by radioembolization
If interventional radiolosists need to direct patients to an online resource on
radioembolization, here is a website that might prove useful…
M
y SIRT Story (http://www.mysirtstory.org.uk) is
the first dedicated UK patient website to provide
information and support to patients, and their
families, about radioembolization or selective internal radiation therapy (SIRT).
My SIRT Story has been developed in response to the
recent decision by the NHS to make the treatment available
to eligible patients in England and Scotland with liver cancer
that has spread from the bowel or arisen in the bile ducts.
My SIRT Story is a resource from the SIRT UK Network
of clinicians and scientists that aims to share best practice,
clinical experiences and patient information. It has been
supported by Sirtex Medical and has been reviewed by
the patient charity Beating Bowel Cancer to ensure that it
provides patient-friendly information.
Ricky Sharma, honorary consultant in Clinical Oncology
at the Oxford University Hospitals NHS Trust and chair of
the SIRT UK Network said, “It can be hard to take in all the
information and to ask questions in a hospital consultation,
especially when it is for a highly specialist cancer treatment
like SIRT. This website is a great place for patients to find
information and support in their own time. I am sure they
will feel reassured by the stories and practical information
offered.”
Patient-friendly content about radioembolization
My SIRT Story is an up-to-date patient resource that
tells the stories of real people with liver cancer and their
experiences with SIRT. The content has been developed to
be as engaging as possible and contains short videos to help
explain SIRT in an easily understandable way. It includes
patient leaflets; patient stories; patient videos and a
before, during and after procedure video that shows an
actual SIRT procedure in progress.