Nabil Khater, Marcel Kap, Rima Sayah, Dimor Elbers and Huib M Vriesendorp
Purpose: To test the reactivity of monoclonal murine IgM and IgG for Tenascin-C (TNC) in formalinized solid human tumors tissue samples and to estimate the radiation dose that Yttrium- 90 labeled murine IgM reactive with TNC can deliver to a solid tumor and tumor containing draining lymph nodes.
Materials and Methods: Using Immunohistochemistry (IHC), mouse anti-human TNC IgM and IgG clones were tested for the detection of TNC in formalin fixed biopsies of patients with Glioblastoma multiforme (GBM), adeno carcinoma of the exocrine pancreas (PaCa)-, breast-, colon-, renal-, ovary- prostate carcinoma, cutaneous-, ocular- melanomas, and Ewing Sarcoma. IHC was performed on all tumors with an n=1, except for PaCa and ocular melanomas, n=11. Monte-Carlo simulation and convolution calculations were used to determine the activity of Y-90 required for delivering 100Gy to a 50 × 50 × 50 mm3 water-equivalent tumor model, assuming a homogeneous distribution of the radioimmunoconjugate throughout the model volume.
Results: IHC has confirmed reactivity of IgM with TNC in all of the tested human solid tumors samples except for ocular melanoma. Positive and negative controls of IgM specificity were used. The dosimetry simulation predicted an Yttrium-90 activity of 217 MBq to deliver a dose of 100Gy to the tumor model with a 6 mm sharp dose fall off in surrounding normal tissues.
Conclusion: Loco-regional control of human solid tumors may be obtained with intra-tumoral administration of radiolabeled IgM targeting TNC. In TNC negative solid tumors such as ocular melanoma, other tumor-specific target(s) need to be identified.
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