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Purpose: The L1 cell adhesion molecule (L1CAM) is considered a valuable target for therapeutic intervention in different types of cancer. Recent studies have shown that anti-L1CAM radioimmunotherapy (RIT) with Cu- and Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts. In this study, we directly compared the therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under equitoxic conditions with the radiolanthanide Lu and the potential alternative Tb in an ovarian cancer therapy model. Methods: Tb was produced by neutron bombardment of enriched Gd targets. Tb and Lu were used for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice using biodistribution experiments and SPECT/CT imaging. After ascertaining the maximal tolerated doses (MTD) the therapeutic impact of 50 % MTD of Lu- and Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour size of subcutaneous IGROV1 tumours. Results: The average number of DOTA ligands per antibody was 2.5 and maximum specific activities of 600 MBq/mg were achieved under identical radiolabelling conditions. RICs were stable in human plasma for at least 48 h. Lu- and Tb-DOTA-chCE7 showed high tumour uptake (37.8-39.0 %IA/g, 144 h p.i.) with low levels in off-target organs. SPECT/CT images confirmed the biodistribution data. Tb-labelled chCE7 revealed a higher radiotoxicity in nude mice (MTD: 10 MBq) than the Lu-labelled counterpart (MTD: 12 MBq). In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6 % for the Tb-DOTA-chCE7 than the Lu-DOTA-chCE7 RIT. Conclusions: Our study is the first to show that anti-L1CAM Tb RIT is more effective compared to Lu RIT in ovarian cancer xenografts. These results suggest that Tb is a promising candidate for future clinical applications in combination with internalising antibodies. [ABSTRACT FROM AUTHOR]

Purpose: The radiolanthanide Tb ( T = 6.90 days, Eβ = 154 keV) was recently proposed as a potential alternative to Lu ( T = 6.71 days, Eβ = 134 keV) due to similar physical decay characteristics but additional conversion and Auger electrons that may enhance the therapeutic efficacy. The goal of this study was to compare Tb and Lu in vitro and in vivo using a tumour-targeted DOTA-folate conjugate (cm09). Methods: Tb-cm09 and Lu-cm09 were tested in vitro on folate receptor (FR)-positive KB and IGROV-1 cancer cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay. In vivo Tb-cm09 and Lu-cm09 (10 MBq, 0.5 nmol) were investigated in two different tumour mouse models with regard to the biodistribution, the possibility for single photon emission computed tomography (SPECT) imaging and the antitumour efficacy. Potentially undesired side effects were monitored over 6 months by determination of plasma parameters and examination of kidney function with quantitative SPECT using Tc-dimercaptosuccinic acid (DMSA). Results: To obtain half-maximal inhibition of tumour cell viability a 4.5-fold (KB) and 1.7-fold (IGROV-1) lower radioactivity concentration was required for Tb-cm09 (IC ~0.014 MBq/ml and ~2.53 MBq/ml) compared to Lu-cm09 (IC ~0.063 MBq/ml and ~4.52 MBq/ml). SPECT imaging visualized tumours of mice with both radioconjugates. However, in therapy studies Tb-cm09 reduced tumour growth more efficiently than Lu-cm09. These findings were in line with the higher absorbed tumour dose for Tb-cm09 (3.3 Gy/MBq) compared to Lu-cm09 (2.4 Gy/MBq). None of the monitored parameters indicated signs of impaired kidney function over the whole time period of investigation after injection of the radiofolates. Conclusion: Compared to Lu-cm09 we demonstrated equal imaging features for Tb-cm09 but an increased therapeutic efficacy for Tb-cm09 in both tumour cell lines in vitro and in vivo. Further preclinical studies using other tumour-targeting radioconjugates are clearly necessary to draw final conclusions about the future clinical perspectives of Tb. [ABSTRACT FROM AUTHOR]