Page 47 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer
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                                Immuno-PET with 89Zr-cMab U36 in head and neck cancer
INTRODUCTION
Radiolabeled monoclonal antibodies (MAb) have shown considerable potential
for diagnosis and treatment of cancer (1,2). In clinical radioimmunoscintigraphy
and radioimmunotherapy studies performed at our institute, the potential of the CD44v6-specific murine MAb (mMAb) U36 for these purposes has been shown. Radioimmunoscintigraphy with technetium-99m (99mTc)-labeled mMAb U36 IgG 3 was found to be as reliable as the radiological imaging techniques computed tomography (CT) and magnetic resonance imaging (MRI) for the detection of
lymph node metastases in patients with head and neck squamous cell carcinoma (HNSCC), but the detection of tumor deposits smaller than 1 cm appeared to be a problem despite the proven accumulation of the MAb in these tumors (3). Subsequently, chimeric MAb (cMAb) U36 was tested in clinical phase I dose escalation radioimmunotherapy trials (4,5). Promising antitumor effects were observed with 186Re-cMAb U36 in HNSCC patients with end-stage disease.
Introduction of immuno-PET, the combination of PET with MAbs, is an attractive option to improve tumor detection because it combines the high sensitivity and resolution of a PET camera with the specificity of a MAb (6-8). The latter might be an advantage in comparison with the currently used PET tracers such as fluorine-18 labeled fluoro-2-deoxy-D-glucose (18FDG), which shows increased uptake not only in tumors but also in normal tissues with high metabolic activity. Apart from its diagnostic capabilities, PET also has potential for quantification of molecular interactions, which is particularly attractive when immuno-PET is used as prelude to antibody-based therapy. First, patients can be selected who have the best chance to benefit from MAb treatment (6-8). Next, in an individualized therapeutic approach, immuno-PET enables the confirmation of tumor targeting and the quantification of MAb accumulation in tumor and normal tissues. For this purpose, we started the coupling of positron emitters to MAbs and a preclinical evaluation of these radiolabeled MAbs in immuno-PET.
For being suitable for immuno-PET, a positron emitter has to fulfill several requirements. Its physical half-life has to be compatible with the time needed for a MAb to achieve optimal tumor-to-nontumor ratios. For intact MAbs, presently the most frequently used format for targeting solid tumors, this time is generally 2 to 4 days.
Two positron emitters with a proper half-life for immuno-PET with intact MAbs are zirconium-89 (89Zr, half-life 78.4 hours) and iodine-124 (124I, half-life
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