The inverse electron-demand Diels-Alder reaction as a new methodology for the synthesis of 225Ac-labelled radioimmunoconjugates.

The inverse electron-demand Diels-Alder reaction between tetrazine (Tz) and trans-cyclooctene (TCO) facilitates the efficient radiosynthesis of 225Ac-labelled radioimmunoconjugates in a two-step method, outperforming conventional approaches based on isothiocyanate couplings.

MANOTA: a promising bifunctional chelating agent for copper-64 immunoPET.

Improved bifunctional chelating agents (BFC) are required for copper-64 radiolabelling of monoclonal antibodies (mAbs) under mild conditions to yield stable, target-specific imaging agents. Four different bifunctional chelating agents (BFC) were evaluated for Fab (Fragment antigen binding) conjugation and radiolabelling with copper-64. Two DOTA- (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and two NOTA- (1,4,7-triazacyclononane-1,4,7-triacetic acid) derivatives bearing a p-benzyl-isothiocyanate group were conjugated to Fab-trastuzumab - which targets the HER2/neu receptor - and the average number of chelators attached ranged from 2.4 to 4.3 macrocycles per Fab. Labelling of the immunoconjugate with copper-64 was achieved in high radiochemical yields after 45 min at 37 °C, and the radiochemical purity of each 64Cu-BFC-Fab-trastuzumab reached 97% after purification. The affinity of each 64Cu-BFC-Fab-trastuzumab ranged between 10 and 50 nM as evaluated by in vitro saturation assays using the HCC1954 breast cancer cell line. PET-MR imaging and biodistribution studies were performed in mice bearing breast cancer BT-474 xenografts. BT-474 tumours were clearly visualized on PET images at 4 and 24 hours post-injection. The tumour uptake of 64Cu-BFC-Fab-trastuzumab reached 8.9 to 12.8% ID g-1 24 hours post-injection and significant differences in non-specific liver uptake were observed depending on the BFC conjugated, the lowest being observed with MANOTA. These results show that MANOTA is a valuable tool for copper-64 radiolabelling.

Reproducibility of trunk isoinertial dynamic performance in patients with low back pain.

The purpose of this study was to assess consistency of response in repeated measurements of isoinertial trunk performance among patients with low back pain. An underlying assumption was that inconsistency can detect lack of effort. Ninety-two patients, 53 men and 39 women, were evaluated using a multiaxis isoinertial dynamometer. The patients were asked to perform with maximum effort against 25 and 50% maximum isometric torque in each plane of motion. Torque, velocity, and range of motion were measured in repeated trials. Correlations between first and second trials were extremely high in all cases even through the range of performance was diverse. Percentage differences between first and second trials were found to be approximately normally (Gaussian) distributed. On the basis of normality, we calculated limits for the percentage difference between first and second trials, within which patients with low back pain would be expected to fall 95% of the time. These limits, presented separately for men and women, are given for each combination of measurements of torque, velocity, and range of motion; plane of motion; and two levels of resistance. Resistance was measured at 25 and 50% of maximum isometric. The limits may be used as guidelines to assess maximum performance for patients with low back pain.