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Published on: January 29, 2019
Radiolabeled immunoglobulin therapy: old barriers and new opportunities
1Marshfield Clinic, 1000 North Oak Avenue, Marshfield, Wisconsin 54449, USA. huriesendo@aol.com
Abstract:
The development of cancer-selective therapies, in particular radiolabeled immunoglobulin therapy (RIT), has stalled. RIT limitations/opportunities are identified in translational research in nude mice, beagles and rhesus monkeys, and in patients with Hodgkin's disease, neurological paraneoplastic syndromes or small vessel vasculitis. Intravenous RIT is most successful in patients with hematological malignancies due to high tumor uptake and long tumor retention of radiolabeled immunoglobulins. Patients with solid tumors are only expected to benefit from RIT by the administration of radiolabeled immunoglobulins directly into the tumor. Tumor-reactive IgG is the best vehicle for i.v. RIT. Tumor-reactive IgM is the best vehicle for intratumoral RIT. The authors do not intend to review the whole clinical RIT experience, but instead analyze the current limitations to success and how they can be circumvented. When the scientific community can reach a consensus on the development and use of these promising and economical radiopharmaceuticals, increasing numbers of patients with recurrent cancer will start to benefit from RIT.
Insights
Radiolabeled immunoglobulin therapy (RIT) shows promise for cancer treatment but faces challenges. Overcoming these limitations, particularly for solid tumors, could expand RIT
Area of Science:
- Oncology
- Radiopharmaceutical Therapy
- Translational Medicine
Background:
- Radiolabeled immunoglobulin therapy (RIT) development has stalled despite its potential for cancer-selective treatment.
- Current RIT successes are primarily in hematological malignancies, with limited efficacy in solid tumors.
Purpose of the Study:
- To analyze the limitations hindering RIT success.
- To identify strategies for overcoming these limitations and improving RIT efficacy.
Main Methods:
- Translational research involving animal models (nude mice, beagles, rhesus monkeys).
- Analysis of clinical RIT data from patients with Hodgkin's disease, paraneoplastic syndromes, and vasculitis.
Main Results:
- Intravenous RIT is effective for hematological cancers due to high radiolabeled immunoglobulin uptake and retention.
- Direct intratumoral administration is necessary for solid tumors, with IgM as the preferred vehicle.
- IgG is the optimal vehicle for intravenous RIT.
Conclusions:
- Consensus on RIT development and application is crucial for patient benefit.
- Addressing current limitations can unlock the potential of RIT for recurrent cancers.
- Economical radiopharmaceuticals can improve outcomes for more cancer patients.
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