Improving the delivery of radionuclides for imaging and therapy of cancer using pretargeting methods.
The article reviews the background and current status of pretargeting for cancer imaging and therapy with radionuclides. Pretargeting procedures were introduced approximately 20 years ago as an alternative to directly radiolabeled antibodies. Because they were multistep processes, they were met with resistance but have since progressed to simple and improved procedures that could become the next generation of imaging and therapy with radionuclides. The separation of the radiolabeled compound from the antibody-targeting agent affords pretargeting procedures considerable flexibility in the radiolabeling process, providing opportunities for molecular imaging using gamma- or positron-emitting radionuclides and a variety of beta- and alpha-emitting radionuclides of therapeutic applications. Pretargeting methods improve tumor/nontumor ratios, exceeding that achieved with directly radiolabeled Fab' fragments, particularly within just a few hours of the radionuclide injection. In addition, tumor uptake exceeds that of a Fab' fragment by as much as 10-fold, giving pretargeting a greatly enhanced sensitivity for imaging. Advances in molecular biology have led to the development of novel binding proteins that have further improved radionuclide delivery in these systems. Studies in a variety of hematologic and solid tumor models have shown advantages of pretargeting compared with directly radiolabeled IgG for therapy, and there are several clinical studies under way that are also showing promising results. Thus, the next generation of targeting agents will likely employ pretargeting approaches to optimize radionuclide delivery for a wide range of applications.
Sharkey
Robert M
RM
Center for Molecular Medicine and Immunology, Belleville, New Jersey 10709, USA. msharkey@gscancer.org
Karacay
Habibe
H
Cardillo
Thomas M
TM
Chang
Chien-Hsing
CH
McBride
William J
WJ
Rossi
Edmund A
EA
Horak
Ivan D
ID
Goldenberg
David M
DM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001360:Avidin / Q000737:chemistry; D001710:Biotin / Q000737:chemistry; D002138:Calibration; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D005720:Gamma Rays; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009841:Oligonucleotides / Q000737:chemistry; D016719:Radioimmunodetection; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000008:administration & dosage* / Q000737:chemistry; D011877:Radionuclide Imaging / Q000379:methods; D011994:Recombinant Proteins / Q000737:chemistry; D019809:Streptavidin / Q000737:chemistry; D013997:Time Factors; D014465:Ultrasonics; D015021:Yttrium Radioisotopes / Q000737:chemistry
D000911:Antibodies, Monoclonal; D003287:Contrast Media; D018076:DNA, Complementary; D007074:Immunoglobulin G; D009841:Oligonucleotides; D011868:Radioisotopes; D011994:Recombinant Proteins; D015021:Yttrium Radioisotopes; D001360:Avidin; D001710:Biotin; D004247:DNA; D019809:Streptavidin