Synthesis and evaluation of 99mTc/ 99Tc-MAG3-biotin conjugates for antibody pretargeting strategies

• Published in: Nuclear medicine and biology Vol. 25; no. 7; pp. 611 - 619
• Main Authors: van Gog, Frank B., Visser, Gerard W.M., Gowrising, Radjish W.A., Snow, Gordon B., van Dongen, Guus A.M.S.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.10.1998; Elsevier
• Subjects: 99mTc-labeled biotin; Animals; Antibody pretargeting; Biodistribution in nude mice; Biological and medical sciences; Biotin - analogs & derivatives; Biotin - chemistry; Contrast media. Radiopharmaceuticals; Drug Stability; Female; Medical sciences; Mice; Mice, Nude; Miscellaneous; Pharmacology. Drug treatments; Plasma stability; Radioactive Tracers; Radioimmunodetection - methods; Radioimmunoscintigraphy; Radioimmunotherapy; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Technetium Tc 99m Mertiatide - analogs & derivatives; Technetium Tc 99m Mertiatide - chemistry; Technetium Tc 99m Mertiatide - pharmacokinetics; Tissue Distribution; 99mTc-labeled biotin; Radioimmunoscintigraphy; Antibody pretargeting; Biodistribution in nude mice; Plasma stability; Radioimmunotherapy; Evaluation; Animal model; Rodentia; Biotin; Technetium; Bioavailability; Immunoradiodiagnosis; Vertebrata; Mammalia; Mouse; Animal; Immunoradiotherapy; Pharmacokinetics; Radiopharmaceuticals; Chemical synthesis
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/S0969-8051(98)00022-5

Four 99mTc-MAG3-biotin conjugates were synthesized to determine their potential use in antibody pretargeting strategies for radioimmunoscintigraphy (RIS). To use these 99mTc-MAG3-biotin conjugates as model compounds for 186Re-MAG3-biotin conjugates for radioimmunotherapy (RIT), nanomolar amounts of 99Tc were added as carrier to 99mTc. The biotin derivatives used for the preparation of the conjugates—biocytin, biotin hydrazide, biotinyl-piperazine, and biotinyl-diaminosuccinic acid—differed at the site that is regarded to be susceptible to hydrolysis by biotinidase present in human plasma. All four conjugates were produced with high radiochemical purity, were stable in PBS, and demonstrated full binding capacity to streptavidin. The 99mTc/ 99Tc-MAG3-labeled biotinyl-piperazine and biotinyl-diaminosuccinic acid conjugates were stable in mouse as well as human plasma, whereas the corresponding biocytin and biotin hydrazide conjugates were rapidly degraded. The biodistribution in nude mice at 30 min after injection was similar for all conjugates, and a rapid blood clearance and high intestinal excretion were both observed. It is concluded that the metabolic routing of a conjugate containing biotin and MAG3 is dominated by these two moieties. For this reason, MAG3-biotin conjugates do not seem suited for pretargeted RIT, for which quantitative and fast renal excretion is a prerequisite to minimize radiation toxicity. However, in a pretargeted RIS approach the 99mTc-MAG3-biotin conjugates might have potential.