Ferid Haddad

A facility for measurements of nuclear cross sections for fast neutron cancer therapy

A facility for measurements of neutron-induced double-differential light-ion production cross-sections, for application within, e.g., fast neutron cancer therapy, is described. The central detectio ...

Tumor Immunotargeting Using Innovative Radionuclides

This paper reviews some aspects and recent developments in the use of antibodies to target radionuclides for tumor imaging and therapy. While radiolabeled antibodies have been considered for many years in this context, only a few have reached the level of routine clinical use. However, alternative radionuclides, with more appropriate physical properties, such as lutetium-177 or copper-67, as well as alpha-emitting radionuclides, including astatine-211, bismuth-213, actinium-225, and others are currently reviving hopes in cancer treatments, both in hematological diseases and solid tumors. At the same time, PET imaging, with short-lived radionuclides, such as gallium-68, fluorine-18 or copper-64, or long half-life ones, particularly iodine-124 and zirconium-89 now offers new perspectives in immuno-specific phenotype tumor imaging. New antibody analogues and pretargeting strategies have also considerably improved the performances of tumor immunotargeting and completely renewed the interest in these approaches for imaging and therapy by providing theranostics, companion diagnostics and news tools to make personalized medicine a reality.

One step purification process for no-carrier-added (64)Cu produced using enriched nickel target

Abstract Copper-64 has found many applications in positron emission tomography (PET). Its half-life allows to use it for dosimetric studies associated to copper-67 targeted radiotherapy in cancer treatment. The use of 64Ni(p,n)64Cu nuclear reaction is known to produce 64Cu in large amount and with a high specific activity. In this study, targets were obtained by electroplating onto a gold backing and a typical target irradiation uses 200ߙnA, 17ߙMeV protons during 30ߙmin. After irradiation, pure copper-64 is obtained using only one chromatographic column. Nickel-64 is removed in a first elution step and cobalt isotopes in a second one. The extraction yield for copper-64 is 9±23% and nickel and cobalt impurities are under the detection limit. A recovery process of nickel-64 has also been developed.

HINDAS A European Nuclear Data Program for Accelerator-Driven Systems

In the HINDAS program, nuclear data in the 20-2000 MeV range are evaluated by means of a combination of nuclear tmodels and well-selected intermediate- and high-energy experiments. A panoply of European accelerators is utilized to provide complete sets of experimental data for iron, lead and uranium over a large energy range. Nuclear model codes are being improved and validated against these new experimental data. This should result in enhanced ENDF-formatted data libraries up to 200 MeV, and cross sections for high-energy transport codes above 200 MeV. The impact of the new data libraries and high-energy models will be directly tested on some important parameters of an accelerator-driven system (ADS). Here, we report the recent progress of the various experimental and theoretical activities in HINDAS.

Immuno-PET for Clinical Theranostic Approaches

Recent advances in molecular characterization of tumors have allowed identification of new molecular targets on tumor cells or biomarkers. In medical practice, the identification of these biomarkers slowly but surely becomes a prerequisite before any treatment decision, leading to the concept of personalized medicine. Immuno-positron emission tomography (PET) fits perfectly with this approach. Indeed, monoclonal antibodies (mAbs) labelled with radionuclides represent promising probes for theranostic approaches, offering a non-invasive solution to assess in vivo target expression and distribution. Immuno-PET can potentially provide useful information for patient risk stratification, diagnosis, selection of targeted therapies, evaluation of response to therapy, prediction of adverse effects or for titrating doses for radioimmunotherapy. This paper reviews some aspects and recent developments in labelling methods, biological targets, and clinical data of some novel PET radiopharmaceuticals.

The ARRONAX Project

A new high-energy and high-intensity cyclotron, ARRONAX, has been set into operation in 2010. ARRONAX can accelerate both negative ions (H- and D-) and positive ions (He++ and HH+). Protons can be accelerated from 30 MeV up to 70 MeV with a maximum beam intensity of 2 × 375 μAe whereas He++ can be accelerated at 68 MeV with a maximum beam current of 70 μAe. The main fields of application of ARRONAX are radionuclide production for nuclear medicine and irradiation of inert or living materials for radiolysis and radiobiology studies. A large part of the beam time will be used to produce radionuclides for targeted radionuclide therapy (copper-67, scandium-47 and astatine-211) as well as for PET imaging (scandium-44, copper-64, strontium-82 for rubidium-82 generators and germanium-68 for gallium-68 generators). Since the beginning of the project a particular interest has been devoted to alpha-radionuclide therapy using complex ligands like antibodies and astatine-211 has been selected as a radionuclide of choice for such type of applications. Associated with appropriate carriers, all these radionuclides will respond to a maximum of unmet clinical needs.

Story of Rubidium-82 and Advantages for Myocardial Perfusion PET Imaging.

Rubidium-82 has a long story, starting in 1954. After preclinical studies in dogs showing that myocardial uptake of this radionuclide was directly proportional to myocardial blood flow (MBF), clinical studies were performed in the 80s leading to an approval in the USA in 1989. From that time, thousands of patients have been tested and their results have been reported in three meta-analyses. Pooled patient-based sensitivity and specificity were, respectively, 0.91 and 0.90. By comparison with 99mTc-SPECT, 82Rb PET had a much better diagnostic accuracy, especially in obese patients with body mass index ≥30 kg/m2 (85 versus 67% with SPECT) and in women with large breasts. A great advantage of 82Rb PET is its capacity to accurately quantify MBF. Quite importantly, it has been recently shown that coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity. Moreover, coronary flow reserve is a functional parameter particularly useful in the estimate of microvascular dysfunction, such as in diabetes mellitus. Due to the very short half-life of rubidium-82, the effective dose calculated for a rest/stress test is roughly equivalent to the annual natural exposure and even less when stress-only is performed with a low activity compatible with a good image quality with the last generation 3D PET scanners. There is still some debate on the relative advantages of 82Rb PET with regard to 99mTc-SPECT. For the last 10 years, great technological advances substantially improved performances of SPECT with its accuracy getting closer to this of 82Rb/PET. Currently, the main advantages of PET are its capacity to accurately quantify MBF and to deliver a low radiation exposure.

Is There an Interest to Use Deuteron Beams to Produce Non-Conventional Radionuclides?

With the recent interest on the theranostic approach, there has been a renewed interest for alternative radionuclides in nuclear medicine. They can be produced using common production routes, i.e., using protons accelerated by biomedical cyclotrons or neutrons produced in research reactors. However, in some cases, it can be more valuable to use deuterons as projectiles. In the case of Cu-64, smaller quantities of the expensive target material, Ni-64, are used with deuterons as compared with protons for the same produced activity. For the Sc-44m/Sc-44g generator, deuterons afford a higher Sc-44m production yield than with protons. Finally, in the case of Re-186g, deuterons lead to a production yield five times higher than protons. These three examples show that it is of interest to consider not only protons or neutrons but also deuterons to produce alternative radionuclides.

Elastic neutron scattering at 96 MeV

A facility for detection of scattered neutrons in the energy interval 50–130 MeV, SCANDAL (SCAttered Nucleon Detection AssembLy), has recently been installed at the 20 – 180‐MeV neutron beam line of The Svedberg Laboratory, Uppsala. Elastic neutron scattering from 12C, 16O, 56Fe, 89Y, and 208Pb has been studied at 96 MeV in the 10 – 70° interval. The results from 12C and 208Pb have recently been published,6 while the data from 16O, 56Fe, and 89Y are under analysis. The achieved energy resolution, 3.7 MeV, is about an order of magnitude better than for any previous experiment above 65 MeV incident energy. The present experiment represents the highest neutron energy where the ground state has been resolved from the first excited state in neutron scattering. A novel method for normalization of the absolute scale of the cross section has been used. The estimated normalization uncertainty, 3%, is unprecedented for a neutron‐induced differential cross section measurement on a nuclear target. The results are com...

Comparison of Immuno-PET of CD138 and PET imaging with 64 CuCl 2 and 18 F-FDG in a preclinical syngeneic model of multiple myeloma

Purpose Although recent data from the literature suggest that PET imaging with [18]-Fluorodeoxyglucose (18F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker in many laboratories for the identification and purification of myeloma cells, and could be used in phenotype tumor imaging. In this study, we evaluated a 64Cu-labeled anti-CD138 murine antibody (64Cu-TE2A-9E7.4) and a metabolic tracer (64CuCl2) for PET imaging in a MM syngeneic mouse model. Experimental Design and Results 64Cu-TE2A-9E7.4 antibody and 64CuCl2 were evaluated via PET imaging and biodistribution studies in C57BL / KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions. These results were compared to 18F-FDG-PET imaging. Autoradiography and histology of representative tumors were secondly conducted. In biodistribution and PET studies, 64Cu-TE2A-9E7.4 displayed good tumor uptake of subcutaneous and intra-medullary lesions, greater than that demonstrated with 18F-FDG-PET. In control experiments, only low-level, non-specific uptake of 64Cu-labeled isotype IgG was observed in tumors. Similarly, low activity concentrations of 64CuCl2 were accumulated in MM lesions. Histopathologic analysis of the immuno-PET–positive lesions revealed the presence of plasma cell infiltrates within the bone marrow. Conclusions 64Cu-labeled anti-CD138 antibody can detect subcutaneous MM tumors and bone marrow lesions with high sensitivity, outperforming 18F-FDG-PET and 64CuCl2 in this preclinical model. These data support 64Cu-anti-CD138 antibody as a specific and promising new imaging radiopharmaceutical agent in MM.