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Radiotherapy is a cancer treatment utilising high doses of ionizing radiation to destroy cancer cells. Our team has pioneered neutron activation of 152Sm, filled and sealed into single-walled (SWCNTs) and multi-walled carbon nanotubes (MWCNTs), to create stable and high-dose radioactive carbon nanocapsules for cancer radiotherapy. In this work, MWCNTs filled with enriched 152SmCl3 (Sm@MWCNTs) were sealed and irradiated, followed by surface functionalisation with an epidermal growth factor receptor (EGFR)-targeting antibody. Characterisation of functionalised Sm@MWCNTs was carried out using thermogravimetric analysis, gel electrophoresis and transmission electron microscopy. The organ biodistribution of the radioactive functionalised 153Sm@MWCNTs and therapeutic efficacy were studied in an experimental melanoma lung metastatic tumour model in mice after intravenous injection. Quantitative biodistribution analyses showed high accumulation of 153Sm@MWCNT-Ab in lung. Significant tumour growth reduction was induced by both treatments of 153Sm@MWCNTs functionalised with or without the antibody after a single intravenous injection. Although EGFR targeting showed no improvement in therapeutic efficacy, reduced spleen toxicity and normal haematological profiles were obtained for both functionalised derivatives. The current study demonstrated the possibility of performing chemical functionalisation and antibody conjugation on radioactive nanocapsules post-irradiation for the preparation of targeted radiopharmaceuticals., This work received funding from the European Union’s Seventh Framework Programme (FP7-ITN Marie-Curie Actions, RADDEL, 290023). PM Costa would like to acknowledge the funding from the Wellcome Trust (WT103913). KT A-J would like to acknowledge the funding from Worldwide Cancer Research, UK (12–1054). This work was partly supported by the Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la Recherche (ANR) through the LabEx project Chemistry of Complex Systems (ANR-10-LABX-0026_CSC), and the International Center for Frontier Research in Chemistry (icFRC). ICMAB and ICN2 acknowledge financial support from the Spanish Ministry of Economy and Competitiveness, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2015-0496 and SEV-2017-0706). We thank Thomas Swan Co. Ltd. for supplying CNT Elicarb® samples. We wish to acknowledge Cathy Royer and Valérie Demais for TEM analyses at the Plateforme Imagerie in Vitro at the Center of Neurochemistry (Strasbourg, France).

The use of three different monoclonal antibodies specific for human ventricular myosin heavy chains in the visualization of the location and extent of necrosis in dogs with experimental acute myocardial infarction and in humans is described. Using a classic immunohistochemical method or ex vivo analysis of heart slices in dogs with acute myocardial infarction subjected to intravenous injection of unlabeled antimyosin antibodies or antimyosin antibodies labeled with indium-111, it was observed that all antibody fragments specifically reached the targeted necrotic zone less than 2 h after antibody injection and remained bound for up to 24 h. In a limited but significant number of cases (5 of the 12 humans and 11 of 43 dogs), it was possible to image the necrotic zone in vivo as early as 2 to 4 h after antibody injection. In other cases, individual blood clearance variations retarded or even prevented in vivo necrosis detection. Higher antimyosin fixation values were obtained in the necrotic zones in dogs with a rapid blood clearance relative to that of the other dogs. It is concluded that antimyosin antibodies always reached necrotic areas within 2 h. If blood clearance was rapid, in vivo imaging of the necrotic area was possible 2 to 6 h after necrosis, even in humans. In some cases, however, uncontrolled individual variations in the timing required for sufficient blood clearance hampered this rapid in vivo detection of myocardial necrosis.

Monoclonal antibodies (MoAbs) 17-1A and 19-9, which specifically bind human colorectal carcinoma (CRC) cells, were tested for their usefulness in localizing colorectal tumors in nude mice. One of the 131I-labeled MoAbs and an irrelevant 125I-labeled immunoglobulin of the same isotype were injected into nude mice simultaneously bearing a human CRC and a human melanoma. The percentage of the injected dose of antibody per gram of tissue, the CRC/tissue ratios of antibody distribution, and the localization indices were calculated at various time intervals (2 h to 9 days). For both MoAbs, labeling to a specific activity of 10 microCi/microgram by the iodogen method gave optimum immunoreactivity. The accumulation of MoAb 17-1A in CRC reached is maximum at 5 days and remained at this level for up to 9 days postinjection. For MoAb 19-9, which detects a circulating antigen shed by the tumor into the serum, the accumulation in the CRC was maximum at 24 h, and decreased thereafter. The CRC/organ ratios and localization indices for both MoAbs increased with time in the CRC tissue, but remained low and unchanged in the melanoma and normal tissues. Using F(ab')2 antibody fragments, faster kinetics with earlier maximum accumulation, higher tumor/organ ratios, and better localization indices were achieved than with intact MoAbs. The data obtained was useful in defining parameters which must be considered before radiolabeled MoAbs are used in cancer patients for diagnostic purposes.