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Functionalized multi-walled carbon nanotubes (MWCNTs) containing radioactive salts are proposed as a potential system for radioactivity delivery. MWCNTs are loaded with isotopically enriched 152-samarium chloride (152SmCl3), the ends of the MWCNTs are sealed by high temperature treatment, and the encapsulated 152Sm is neutron activated to radioactive 153Sm. The external walls of the radioactive nanocapsules are functionalized through arylation reaction, to introduce hydrophilic chains and increase the water dispersibility of CNTs. The organ biodistribution profiles of the nanocapsules up to 24 h are assessed in naïve mice and different tumor models in vivo. By quantitative γ-counting, 153SmCl3@MWCNTs-NH2 exhibite high accumulation in organs without leakage of the internal radioactive material to the bloodstream. In the treated mice, highest uptake is detected in the lung followed by the liver and spleen. Presence of tumors in brain or lung does not increase percentage accumulation of 153SmCl3@MWCNTs-NH2 in the respective organs, suggesting the absence of the enhanced permeation and retention effect. This study presents a chemical functionalization protocol that is rapid (∼one hour) and can be applied to filled radioactive multi-walled carbon nanocapsules to improve their water dispersibility for systemic administration for their use in targeted radiotherapy., We thank Thomas Swan & Co. Ltd for supplying the Eli-carb® MWCNTs. This work was supported by European Union's Seventh Framework Programme FP7, Project “RADDEL” [grant number 290023], Worldwide Cancer Research [grant number 12-1054], Biotechnology and Biological Sciences Research Council [grant number BB/J008656/1], European Union HORIZON 2020 MSCA RISE 2016, Project Carbo-Immap [grant number 734381], “Severo Ochoa” Programme for Centres of Excellence in R&D [grant numbers SEV-2015-0496, SEV-2017-0706], and Generalitat de Catalunya 2017 [grant number SGR 327]., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

Radiation therapy along with chemotherapy and surgery remain the main cancer treatments. Radiotherapy can be applied to patients externally (external beam radiotherapy) or internally (brachytherapy and radioisotope therapy). Previously, nanoencapsulation of radioactive crystals within carbon nanotubes, followed by end-closing, resulted in the formation of nanocapsules that allowed ultrasensitive imaging in healthy mice. Herein we report on the preparation of nanocapsules initially sealing “cold” isotopically enriched samarium (152Sm), which can then be activated on demand to their “hot” radioactive form (153Sm) by neutron irradiation. The use of “cold” isotopes avoids the need for radioactive facilities during the preparation of the nanocapsules, reduces radiation exposure to personnel, prevents the generation of nuclear waste, and evades the time constraints imposed by the decay of radionuclides. A very high specific radioactivity is achieved by neutron irradiation (up to 11.37 GBq/mg), making the “hot” nanocapsules useful not only for in vivo imaging but also therapeutically effective against lung cancer metastases after intravenous injection. The high in vivo stability of the radioactive payload, selective toxicity to cancerous tissues, and the elegant preparation method offer a paradigm for application of nanomaterials in radiotherapy., This work received funding from the European Union’s Seventh Framework Programme (FP7-ITN Marie-Curie Actions, RADDEL, 290023). K.T.A.-J. acknowledges funding from Worldwide Cancer Research (12-1054), M.K. from MEYS (LTC18039), and G.T. from Agaur (2017 SGR 581). 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). This work was partly supported by the Centre National de la Recherche Scientifique (CNRS), by the Agence Nationale de la Recherche (ANR) through the LabEx project Chemistry of Complex Systems (ANR-10-LABX-0026_CSC), and by the International Center for Frontier Research in Chemistry (icFRC). We acknowledge support by MEYS CR and EU -ESIF in the frame of Operational Programme Research Development and Education - project Pro-NanoEnviCz (Project No. CZ.02.1.01/0.0/0.0/16_013/0001821). We thank Thomas Swan Co. Ltd. for supplying CNT Elicarb samples. We are grateful to S. Sandoval (ICMAB) and C. Ramos (IQS-ICMAB) for assessing the length and diameter distribution of CNTs.

Iodobenzamide (IBZM) and iodolisuride (ILIS), which belong to different chemical families, are two radioligands used for SPECT imaging of dopamine D2 receptors. We have compared their cerebral biodistribution in control rats and their ability to detect quantitative modifications of D2 receptors in experimental models. IBZM and ILIS have a similar cerebral distribution in vivo in control rats and permitted the detection of upregulation of striatal dopamine D2 receptors in a model of chronic haloperidol treatment. Moreover, we observed that 1 h after injection of a saturating dose of haloperidol, IBZM uptake was 72% displaced from the striatum, while ILIS uptake was 50% displaced. In an experimental model of excitotoxic striatal lesion, the in vivo accumulation of IBZM was 30% decreased on the lesioned side, in agreement with a decrease in dopamine D2 receptor density. By contrast, the accumulation of ILIS was identical in the lesioned and in the intact striatum. From the results, it appears that IBZM and ILIS, which are both used to image dopamine D2 receptors in vivo, behave differently in pathological experimental models. The ligand for human exploration should then be chosen according to the suspected pathology.

The Hodgkin associated monoclonal antibody (Mab) HRS-1 reacts with Hodgkin and Reed-Sternberg cells (HR-S) in all HD subtypes. HRS-1 Mab was labelled with radioiodine and injected into 10 patients for immunoscintigraphy (IS). Seven patients were injected with HRS-1 Mab radiolabelled with 131I and three patients were injected with HRS-1 Mab labelled with 123I. A control anti-alpha-fetoprotein (anti-AFP) Mab was radiolabelled with another iodine isotope and was injected simultaneously in five cases. Six out of eight patients with proven HD had a true positive scan (nodal, splenic and bony involvement). Imaging was equivocal or failed in the two other patients. In the last two patients IS imaging was truly negative due to the absence of residual HD in one patient and to an erroneous histological diagnosis of HD in another patient. These results, although preliminary, demonstrate that IS with radioiodine-labelled HRS-1 Mab is feasible and may prove to be informative in the staging of HD.

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.