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The 18-membered macrocycle H macropa was investigated for Ac chelation in targeted alpha therapy (TAT). Radiolabeling studies showed that macropa, at submicromolar concentration, complexed all Ac (26 kBq) in 5 min at RT. [ Ac(macropa)] remained intact over 7 to 8 days when challenged with either excess La ions or human serum, and did not accumulate in any organ after 5 h in healthy mice. A bifunctional analogue, macropa-NCS, was conjugated to trastuzumab as well as to the prostate-specific membrane antigen-targeting compound RPS-070. Both constructs rapidly radiolabeled Ac in just minutes at RT, and macropa-Tmab retained>99 % of its Ac in human serum after 7 days. In LNCaP xenograft mice, Ac-macropa-RPS-070 was selectively targeted to tumors and did not release free Ac over 96 h. These findings establish macropa to be a highly promising ligand for Ac chelation that will facilitate the clinical development of Ac TAT for the treatment of soft-tissue metastases.

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Three analytical studies of base-isolated structures are carried out. First, six pairs of near-fault motions oriented in directions parallel and normal to the fault were considered, and the average of the response spectra of these earthquake records was obtained. This study shows that in addition to pulsetype displacements, these motions contain signiÿcant energy at high frequencies and that the real and pseudo-velocity spectra are quite di erent.The second analysis modelled the response of a model of an isolated structure with a exible superstructure to study the e ect of isolation damping on the performance of di erent isolation systems under near-fault motion. The results show that there exists a value of isolation system damping for which the superstructure acceleration for a given structural system attains a minimum value under near-fault motion. Therefore, although increasing the bearing damping beyond a certain value may decrease the bearing displacement, it may transmit higher accelerations into the superstructure.Finally, the behaviour of four isolation systems subjected to the normal component of each of the near-fault motions were studied, showing that EDF type isolation systems may be the optimum choice for the design of isolated structures in near-fault locations.