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Molecular imaging with radiolabeled anti-HER2 nanobodies for improved diagnosis and follow-up of breast cancer - the road to clinical translation

Tuesday, 27 September, 2011 - 17:00
Campus: Brussels Health Campus
Faculty: Medicine and Pharmacy
auditorium P. Brouwer
Ilse Vaneycken
phd defence

Nanobodies, the smallest intact antigen-binding
fragments isolated from heavy-chain camelidae
antibodies, can target cancer-associated antigens
with high specificity. Besides their small size,
they are stable, soluble and rapidly eliminated
from the bloodstream, all ideal characteristics for
molecular imaging probes. We hypothesize that
non-invasive molecular imaging of HER2
expression with a radiolabeled anti-HER2
nanobody will offer superior diagnostic
performance. The procedure is fast, painless and
sampling errors with biopsies are avoided. The
imaging procedure can be repeated multiple
times so that HER2 overexpression can also be
monitored during the disease process. This allows
to select patients that are susceptible to a
targeted therapy and to monitor the therapy
response. In patients that do not have HER2
positive breast cancer, expensive and potentially
toxic treatment can be avoided. The aim of this
thesis is to evaluate radiolabeled HER2-targeting
nanobodies in a preclinical setting, focused on the
final endpoint to provide a new
radiopharmaceutical that can be translated to a
clinical setting for molecular PET imaging of HER2
in breast cancer patients. The thesis is outlined in
four parts: Although nanobodies are considered
to be low immunogenic, in the first part we
investigate if further humanization of nanobodies
is feasible. A second part is aimed at a preclinical
screening of different anti-HER2
nanobodies to select the lead compound for a
phase I clinical trial. In a third and fourth part,
we propose methods to label the lead nanobody
with 68Ga and 18F for PET applications.

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