A Review of the Intravenous Administration of Radiolabeled Immunoglobulin G to Cancer Patients. High or Low Protein Dose?

Abstract

This retrospective analysis of preclinical and clinical radiolabeled immunoglobulin studies focuses on three well-known observations:

1. IV tumor reactive IgG provides higher response rates in patients with hematological malignancies than in patients with solid tumors

2. Patients with CD20 positive B cell lymphoma require a high IV IgG protein dose for effective tumor targeting

3. Most patients experience high uptake of IV administered radiolabeled IgG in normal liver.

This review supports the following new hypotheses:

1. The blood-tumor barrier in most solid tumors is higher than in most hematological malignancies

2. The blood-tumor barrier in CD20 positive B cell lymphomas is lowered by the IV administration of high doses [> 100 mg] of anti-CD20 IgG, presumably due to IgG induced intra-tumoral production of vaso-active biological response modifiers

3. The blood-tumor barrier is low in Hodgkin's disease, presumably due to the continuous and innate production of biological response modifiers in tissues containing Hodgkin's disease

4. The uptake of tumor reactive IgG in the normal liver is controlled by the Fc portion of the IgG. The radioimmunoconjugate is not catabolized in the liver. This appears to indicate that the F_c portion of the IgG binds to the MHC class I like, F_cγRn receptors in liver endothelium and hepatocytes and not to F_cγ RI, RII or RIII receptors

The new hypotheses require verification and can be instrumental in the design of new more effective clinical RIT studies.