Preclinical testing of radiopharmaceuticals for novel applications in HIV, bacterial and fungal infectious diseases.

Abstract

Antibiotics, antifungal and antiviral medications have traditionally been used in the management of infections. Due to widespread emergence of resistance to antimicrobial medications, and their side effects, there is a growing need for alternative approaches for management of such conditions. Antibiotic resistant bacterial pathogens are on the rise. A cure has not been achieved for viral infections like AIDS, while fungal and parasitic infections are constant threats to the health of general public. The incidence of opportunistic infections in immunocompromised individuals like HIV patients, patients receiving high dose steroids, chemotherapy patients, and organ transplant recipients is on the rise. Radioimmunotherapy (RIT) has the potential to be a suitable and viable therapeutic modality in the arena of infection management. Provided the target-associated antigen is expressed by the target cells and minimally or not expressed by other tissues, selective targeting of radiation to target sites can be theoretically accomplished with relative sparing normal tissues from radiation exposure. In our laboratory we successfully demonstrated the effectiveness of RIT for treating infectious diseases. We targeted murine cryptococcosis with a mAb to the Cryptococcus neoformans capsular glucuronoxylomannan labeled with Bismuth-213 ((213)Bi) or Rhenium-188 ((188)Re). We subsequently extended the applicability of RIT for treating bacterial and viral infections. One of the advantages of using RIT to treat infections as opposed to cancer is that, in contrast to tumor cells, cells expressing microbial antigens are antigenically very different from host tissues and thus provide the potential for exquisite specificity and low cross-reactivity. Ever increasing incidence of infectious pathologies, exhaustion of antimicrobial possibilities and rising drug resistance calls for use of alternative and novel therapeutic options and we believe RIT is the need of the hour to combat these infections.

• Authors: M Shah, G Garg, E Dadachova
• Journal: The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... (Q J Nucl Med Mol Imaging) Vol. 59 Issue 3 Pg. 317-26 (Sep 2015) ISSN: 1827-1936 [Electronic] Italy
• PMID: 26200222 (Publication Type: Journal Article, Review)

Chemical References

• Antibodies, Monoclonal
• Radioisotopes
• Radiopharmaceuticals
• Rhenium
• Bismuth

Topics

• Animals
• Antibodies, Monoclonal (chemistry)
• Bacterial Infections (diagnostic imaging, radiotherapy)
• Bismuth (therapeutic use)
• Cryptococcosis (radiotherapy)
• Cryptococcus neoformans
• Drug Evaluation, Preclinical
• HIV Infections (diagnostic imaging, radiotherapy)
• Humans
• Mice
• Mice, Inbred C57BL
• Mycoses (diagnostic imaging, radiotherapy)
• Radioimmunotherapy (methods)
• Radioisotopes (therapeutic use)
• Radionuclide Imaging
• Radiopharmaceuticals (therapeutic use)
• Rhenium (therapeutic use)
• Tissue Distribution