High dose rhenium-186-labeling of monoclonal antibodies for clinical application: pitfalls and solutions.

BACKGROUND. Rhenium-186 ( 188 Re) has ideal properties for adjuvant radioimmunotherapy (RIT). However, the lack of suitable methods for high dose 188 Re labeling of monoclonal antibodies (MAbs) has hampered the use of 188 Re in clinical RIT. After development ofa chemically identical multistep procedure for the production of 188 Re-MAG 3 -MAb and 99m Tc/ 99 Tc-MAGj-MAb conjugates for use as a matched pair, the authors now report on further progress to make this labeling method broadly applicable for high dose 188 Re labeling. METHODS. The number of metal-MAG 3 groups that can be coupled to a MAb without alteration of the biodistribution was investigated by radioimm moscintigraphy (RIS) in patients with head and neck squamous cell carcinomas (HNSCC). For labeling with 500 mCi [ 186 Re]ReO 4 - , an efficient chemoprotection was introduced to suppress the damaging effects of radiation during conjugation and conjugate purification. Furthermore, the authors developed strategies thay make the procedure easy and safe to perform at any medical center. RESULTS. MAbs showed a minor variation in biodistribution in HNS(lC patients when the number of metal-chelate groups per MAb varied between. II and 4.3. High dose 186 Re-MAb conjugates (150-250 mCi) with a Re-MAG 3 :M tb ratio of 3.4 were obtained with a radiochemical purity of >95% and minima aggregate formation (<6%). Furthermore, a semiautomated labeling device and a convenient 100 mCi labeling kit in the form of a dried Re-MAG 3 -TFP ester were developed. HIT studies in HNSCC-bearing nude mice showed that high dose 180 Re-labeled MAb U36 is more effective than iodine-131-labeled MAb U36. CONCLUSIONS. High dose 186 Re-MAb conjugates were prepared that exhibit an optimal stability, immunoreactivity, and pharmacokinetic behavior. The availability of a kit procedure for coupling 188 Re to MAbs might open the possibility of a broad application of 186 Re in RIT.