Radiolabeled Immunoglobulin Therapy for Patients with Solid Tumors

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 Yttrium90 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-, ovaryprostate carcinoma, cutaneous-, ocularmelanomas, 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. Prior experience with radiolabeled IgG reactive with human TNC Riva and Reardon [7,8] treated patients with recurrent GBM by administering Iodine-131 labeled IgG reactive with human TNC, in the cyst created by the surgical resection of the recurrence. Survival of patients after I-131-IgG administration was often longer than the tumor response duration after initial treatment with surgical resection, post-op radiation and chemotherapy. The I-131 IgG radiation dose to the recurrence could not be determined accurately at the time and might have been too low for cures. Moreover, the gamma emissions of I-131 are too weak to deliver a homogeneous tumor dose and radioactive iodine is enzymatically removed from carrier molecules and taken up in the thyroid gland of the patient or secreted into the stomach of the patient [4, 5]. RIT studies in patients with Hodgkin’s disease and nonHodgkin’s Lymphoma In the past, RIT has benefited patients with ‘liquid’ tumors, such as Hodgkin’s disease (HD) and B-cell non-Hodgkin’s lymphoma [5,9-13]. A low intravenous dose of 2 mg of anti-ferritin rabbit IgG labeled with Citation: Khater N, Kap M, Sayah R, Elbers D, Vriesendorp HM (2017) Radiolabeled Immunoglobulin Therapy for Patients with Solid Tumors. J Nucl Med Radiat Ther 8: 338. doi: 10.4172/2155-9619.1000338