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Immunomedics,
Inc.
, a biopharmaceutical company primarily focused on the
development of monoclonal antibody-based products for the targeted treatment
of cancer, autoimmune and other serious diseases, today announced the
development of a pretargeting system that can detect and optically image a
tumor during surgery. Results from this preclinical study were presented by
Dr. Mark Rijpkema of the Department of Nuclear Medicine, Radboud University
Nijmegen Medical Centre, Nijmegen, The Netherlands.
While tumor detection with specific radiotracers may be a useful tool for
accurate localization and resection during surgery, these procedures could
benefit from the addition of an optical tracer, since this may allow for more
accurate delineation of the tumor and resection margins. Both tracers in such
a dual modality approach need to show high specificity and a high
tumor-to-background ratio (TBR).
The pretargeting system that the Company is pursuing involves the bispecific
antibody, TF2, which targets the carcinoembryonic antigen (CEA), specifically
CEACAM5, expressed in many human cancers, including breast, colorectal and
lung cancer, and which is also being used in its IMMU-130 antibody-drug
conjugate in clinical trials. Created by the Company's proprietary
DOCK-AND-LOCK™ method, the bispecific antibody is currently in a number of
clinical trials for pretargeted immunoPET imaging and radioimmunotherapy of
patients with CEA-expressing cancers.
The other component of the pretargeting system is a small peptide bearing both
the fluorescent dye, IRdye800CW, and a linker called DOTA for radiolabeling.
Designated as RDC-018, this new peptide was derived from an earlier peptide,
IMP288, that has been used successfully in pretargeting with a number of
radioisotopes such as indium-111 (^111In), yttrium-90, lutetium-177 and
iodine-124.
The goal of this preclinical study was to assess the potential utility of this
peptide for cancer detection by both optical (light) and radionuclide imaging,
starting with an assessment of the radiolabeling procedure for RDC-018, and
leading into in vivo biodistribution and tumor localization properties in a
pretargeting setting compared to the ^111In-IMP288. Animals bearing
subcutaneous CEA-positive human colonic tumors and CEA-negative human renal
cell tumors were used.
Biodistribution study of the RDC-018 peptide showed specific CEA-expressing
tumor targeting with clearance via the kidneys similar to IMP288. Despite
differences in renal uptake, RDC-018, with its ability to be imaged by both
scintigraphic and optical methods, provided high tumor targeting and excellent
TBR, illustrating the feasibility of this dual modality imaging approach.
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