155Tb production by cyclotrons: what level of 155Gd enrichment allows clinical applications?

BACKGROUND: 155Tb represents a potentially useful radionuclide for diagnostic medical applications, but its production remains a challenging problem, in spite of the fact that many production routes have been already investigated and tested. A recent experimental campaign, conducted with low-energy proton beams impinging on a 155Gd target with 91.9% enrichment, demonstrated a significant co-production of 156gTb, a contaminant of great concern since its half-life is comparable to that of 155Tb and its high-energy γ emissions severely impact on the dose released and on the quality of the SPECT images. In the present investigation, the isotopic purity of the enriched 155Gd target necessary to minimize the co-production of contaminant radioisotopes, in particular 156gTb, was explored using various computational simulations. RESULTS: Starting from the recent experimental data obtained with a 91.9% 155Gd-enriched target, the co-production of other Tb radioisotopes besides 155Tb has been theoretically evaluated using the Talys code. It was found that 156Gd, with an isotopic content of 5.87%, was the principal contributor to the co-production of 156gTb. The analysis also demonstrated that the maximum amount of 156Gd admissible for 155Tb production with a radionuclidic purity higher than 99% was 1%. A less stringent condition was obtained through computational dosimetry analysis, suggesting that a 2% content of 156Gd in the target can be tolerated to limit the dose increase to the patient below the 10% limit. Moreover, it has been demonstrated that the imaging properties of the produced 155Tb are not severely affected by this level of impurity in the target. CONCLUSIONS: 155Tb can be produced with a quality suitable for medical applications using low-energy proton beams and 155Gd-enriched targets, if the 156Gd impurity content does not exceed 2%. Under these conditions, the dose increase due to the presence of contaminant radioisotopes remains below the 10% limit and good quality images, comparable to those of 111In, are guaranteed.

The innovative 52g Mn for positron emission tomography (PET) imaging: Production cross section modeling and dosimetric evaluation.

BACKGROUND: Manganese is a paramagnetic element suitable for magnetic resonance imaging (MRI) of neuronal function. However, high concentrations of Mn2 + can be neurotoxic. 52g Mn may be a valid alternative as positron emission tomography (PET) imaging agent, to obtain information similar to that delivered by MRI but using trace levels of Mn2 + , thus reducing its toxicity. Recently, the reaction n a t $^{nat}$ V(α,x)52g Mn has been proposed as a possible alternative to the standard n a t $^{nat}$ Cr(p,x)52g Mn one, but improvements in the modeling were needed to better compare the two production routes. PURPOSE: This work focuses on the development of precise simulations and models to compare the 52g Mn production from both reactions in terms of amount of activity and radionuclidic purity (RNP), as well as in terms of dose increase (DI) due to the co-produced radioactive contaminants, versus pure 52g MnCl2 . METHODS: The nuclear code Talys has been employed to optimize the n a t $^{nat}$ V(α,x)52g Mn cross section by tuning the parameters of the microscopic level densities. Thick-target yields have been calculated from the expression of the rates as energy convolution of cross sections and stopping powers, and finally integrating the time evolution of the relevant decay chains. Dosimetric assessments of [ x x $^{xx}$ Mn]Cl2 have been accomplished with OLINDA software 2.2.0 using female and male adult phantoms and biodistribution data for 52g MnCl2 in normal mice. At the end, the yield of x x $^{xx}$ Mn radioisotopes estimated for the two production routes have been combined with the dosimetric results, to assess the DI at different times after the end of the irradiation. RESULTS: Good agreement was obtained between cross-section calculations and measurements. The comparison of the two reaction channels suggests that n a t $^{nat}$ V(α,x)52g Mn leads to higher yield and higher purity, resulting in more favorable radiation dosimetry for patients. CONCLUSIONS: Both n a t $^{nat}$ V(α,x) and n a t $^{nat}$ Cr(p,x) production routes provide clinically acceptable 52g MnCl2 for PET imaging. However, the n a t $^{nat}$ V(α,x)52g Mn reaction provides a DI systematically lower than the one obtainable with n a t $^{nat}$ Cr(p,x)52g Mn and a longer time window in which it can be used clinically (RNP ≥ 99%).

The modeling of the reaction cross sections in the production of teranositic radionuclides / La modelación de las secciones eficaces de reacción en la producción de radionúclidos teranosíticos

Abstract We utilize various nuclear reaction codes with the aim to guide, interpret, and support the experiments in the proton-induced production measurements of radionuclides for the development of innovative radio-pharmaceuticals. The understanding of reaction cross sections at low-intermediate energies is crucial in this context and requires the knowledge of nuclear models available in different codes, such as EMPIRE, TALYS, and FLUKA. These nuclear reaction codes serve as tool to interpret the measurement of production cross-sections and to complete the measurements with estimates of production of contaminants and/or stable isotopes that are difficult to measure. We illustrate different model calculations to simulate isotope production useful in experiments devoted to the measurement of proton-induced production of the two theranostic radio-isotopes 67Cu and 47Sc.

Resumen Utilizamos varios códigos de reacción nuclear con el objetivo de guiar, interpretar y respaldar los experimentos en las mediciones de producción de radionúclidos inducidas por protones para el desarrollo de productos radio-farmacéuticos innovadores. La comprensión de las secciones eficaces de reacción en energías intermedias bajas es crucial en este contexto y requiere el conocimiento de modelos nucleares disponibles en diferentes códigos, como EMPIRE, TALYS y FLUKA. Estos códigos de reacción nuclear sirven como herramienta para interpretar la medición de secciones eficaces de producción y para completar las mediciones con estimaciones de producción de contaminantes y / o isótopos estables que son difíciles de medir. Ilustramos diferentes cálculos de modelos para simular la producción de isótopos útiles en experimentos dedicados a la medición de la producción inducida por protones de los dos isótopos teranósticos 67Cu y 47Sc.

Cyclotron production of 67Cu: A new measurement of the 68Zn(p,2p)67Cu, 68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga nuclear cross sections

The cross sections of the 68Zn(p,2p)67Cu,68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga reactions were measured at the ARRONAX facility by using the 70 MeV cyclotron, with particular attention to the production of the theranostic radionuclide 67Cu. Enriched 68Zn material was electroplated on silver backing and exposed to alow-intensity proton beam by using the stacked-foils target method. Since 67Cu and 67Ga radionuclides have similar half-lives and same γ-lines (they both decay to 67Zn), a radiochemical process aimed at Cu/Ga separation was mandatory to avoid interferences in γ-spectrometry measurements. A simple chemical procedure having a high separation efficiency (>99%)was developed and monitored during each foil processing, thanks to the tracer isotopes 61Cu and 66Ga.Nuclear cross sections were measured in the energy range 35-70 MeV by using reference reactions recommended by the International Atomic Energy Agency (IAEA) to monitor beam flux. In comparison with literature data a general good agreement on the trend of the nuclear reactions was noted, especially with latest measurements, but slightly lower values were obtained in case of 67Cu. Experimental results of the 68Zn(p,2p)67Cu,68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga reactions were also compared with the theoretical values estimated by using the nuclear reaction code TALYS. The production yield of the theranostic radionuclide 67Cu was estimated considering the results obtained in this work.

Las secciones eficaces de las reacciones 68Zn (p, 2p) 67Cu, 68Zn (p, 2n) 67Ga y 68Zn (p, 3n) 66Ga se midieron en la instalación ARRONAX utilizando el ciclotrón 70 MeV, con especial atención a la producción del radionucleidos teranóstico 67Cu. El material enriquecido 68Zn se galvanizó sobre soporte de plata y se expuso a un haz de protones de baja intensidad utilizando un blanco de láminas apiladas. Como los radionucleidos 67Cu y 67Ga tienen periodos de semidesintegración y líneas γ similares (ambos se desintegran a 67Zn), un proceso radioquímico dirigido a la separación Cu / Ga fue obligatorio para evitar interferencias en las mediciones de espectrometría γ. Se desarrolló un procedimiento químico simple con una alta eficiencia de separación (> 99%) durante cada procesamiento de la lámina, gracias a los isótopos trazadores 61Cu y 66Ga. Las secciones eficaces nucleares se midieron en el rango de energía de 35-70 MeV utilizando reacciones de referencia recomendadas por el Organismo Internacional de Energía Atómica (OIEA) para monitorear el flujo del haz. Al comparar con los datos de la literatura, se observó una buena concordancia en general con la tendencia de las reacciones nucleares, particularmente con las últimas mediciones, pero se obtuvieron valores ligeramente inferiores en el caso de 67Cu. Los resultados experimentales de las reacciones 68Zn (p, 2p) 67Cu, 68Zn (p, 2n) 67Ga y 68Zn (p, 3n) 66Ga también se compararon con los valores teóricos estimados usando el código de reacción nuclear TALYS. El rendimiento de producción del radionucleido teranóstico 67Cu se estimó considerando los resultados obtenidos en este trabajo.

Cyclotron production of 67Cu: A new measurement of the 68Zn(p,2p)67Cu, 68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga nuclear cross sections / Producción de 67Cu en ciclotrón: una nueva medición de secciones eficaces nucleares de 68Zn(p,2p)67Cu, 68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga

Abstract The cross sections of the 68Zn(p,2p)67Cu,68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga reactions were measured at the ARRONAX facility by using the 70 MeV cyclotron, with particular attention to the production of the theranostic radionuclide 67Cu. Enriched 68Zn material was electroplated on silver backing and exposed to alow-intensity proton beam by using the stacked-foils target method. Since 67Cu and 67Ga radionuclides have similar half-lives and same γ-lines (they both decay to 67Zn), a radiochemical process aimed at Cu/Ga separation was mandatory to avoid interferences in γ-spectrometry measurements. A simple chemical procedure having a high separation efficiency (>99%)was developed and monitored during each foil processing, thanks to the tracer isotopes 61Cu and 66Ga.Nuclear cross sections were measured in the energy range 35-70 MeV by using reference reactions recommended by the International Atomic Energy Agency (IAEA) to monitor beam flux. In comparison with literature data a general good agreement on the trend of the nuclear reactions was noted, especially with latest measurements, but slightly lower values were obtained in case of 67Cu. Experimental results of the 68Zn(p,2p)67Cu,68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga reactions were also compared with the theoretical values estimated by using the nuclear reaction code TALYS. The production yield of the theranostic radionuclide 67Cu was estimated considering the results obtained in this work.

Resumen Las secciones eficaces de las reacciones 68Zn (p, 2p) 67Cu, 68Zn (p, 2n) 67Ga y 68Zn (p, 3n) 66Ga se midieron en la instalación ARRONAX utilizando el ciclotrón 70 MeV, con especial atención a la producción del radionucleidos teranóstico 67Cu. El material enriquecido 68Zn se galvanizó sobre soporte de plata y se expuso a un haz de protones de baja intensidad utilizando un blanco de láminas apiladas. Como los radionucleidos 67Cu y 67Ga tienen periodos de semidesintegración y líneas γ similares (ambos se desintegran a 67Zn), un proceso radioquímico dirigido a la separación Cu / Ga fue obligatorio para evitar interferencias en las mediciones de espectrometría γ. Se desarrolló un procedimiento químico simple con una alta eficiencia de separación (> 99%) durante cada procesamiento de la lámina, gracias a los isótopos trazadores 61Cu y 66Ga. Las secciones eficaces nucleares se midieron en el rango de energía de 35-70 MeV utilizando reacciones de referencia recomendadas por el Organismo Internacional de Energía Atómica (OIEA) para monitorear el flujo del haz. Al comparar con los datos de la literatura, se observó una buena concordancia en general con la tendencia de las reacciones nucleares, particularmente con las últimas mediciones, pero se obtuvieron valores ligeramente inferiores en el caso de 67Cu. Los resultados experimentales de las reacciones 68Zn (p, 2p) 67Cu, 68Zn (p, 2n) 67Ga y 68Zn (p, 3n) 66Ga también se compararon con los valores teóricos estimados usando el código de reacción nuclear TALYS. El rendimiento de producción del radionucleido teranóstico 67Cu se estimó considerando los resultados obtenidos en este trabajo.

Application of the "All-on-Four" concept and guided surgery in a mandible treated with a free vascularized fibula flap.

In this article, we describe the first case in the literature in which 3D computer-assisted treatment planning and guided surgery enabled a patient affected by extreme paraphysiologic mandibular bone atrophy to be treated with a free vascularized fibula flap and, after a period of healing, the flapless installation of 4 immediately loaded dental implants. The computer-fabricated surgical guide allowed placement of the implants according to the "All-on-Four" concept in a proper spatial preplanned position and by tilting 1 implant, avoiding an area of bone discontinuity. Additionally, this technique allowed the production of a prefabricated temporary prosthesis, delivered after implant insertion, which could be immediately loaded. The use of a fibula flap makes it possible to create greater bone thickness while computer-assisted treatment planning and guided surgery provide several advantages over the traditional technique.

Computer-assisted surgery: double surgical guides for immediate loading of implants in maxillary postextractive sites.

Implant-supported prostheses are a predictable treatment of totally edentulous patients. Progresses in implantology allowed realizing prostheses that are supported by immediately loading implants. Implants can be inserted in the healed site as fresh extraction sites, without differences about long-term results. Using computer-assisted surgery, it is possible to insert implants in a predetermined position and to create a prostheses, which can be immediately fixed on the implants. Patients have major comfort and an immediate aesthetic and functional result. The use of computer-assisted surgery in fresh extraction sites is a procedure that has not been evaluated because of technical difficulties: teeth extraction eliminates references for surgical guides. The absence of guidelines to treat dentulous areas is often likely caused by lack of computer-assisted surgery: we attempted to use this procedure to replace residual teeth with an immediate implant prosthetic rehabilitation. The aim of this clinical report was to show the possibility to apply computer-assisted surgery in dentulous patient using a double surgical template: one before extraction and the other after extraction of selected teeth.

Zygomatic and maxillary implants inserted by means of computer-assisted surgery in a patient with a cleft palate.

This report describes the possibility of treating a patient affected by unilateral cleft palate and an extremely atrophied edentulous maxilla using zygomatic implants inserted in a conventional manner and maxillary implants inserted by means of a computer-assisted surgery. A cross-arch prosthesis supported by 4 maxillary and 2 zygomatic implants may be an ideal mode of prosthetic rehabilitation for these kinds of patients. The use of zygomatic implants is essential to optimize load distribution and to increase prosthesis stability, whereas the use of computer-assisted surgery facilitates surgical procedures and makes it possible to improve patient satisfaction.

Computer-assisted surgery in the lower jaw: double surgical guide for immediately loaded implants in postextractive sites-technical notes and a case report.

Computer-assisted surgery is based on computerized tomography (CT) scan technology to plan the placement of dental implants and a computer-aided design/computer-aided manufacturing (CAD-CAM) technology to create a custom surgical template. It provides guidance for insertion implants after analysis of existing alveolar bone and planning of implant position, which can be immediately loaded, therefore achieving esthetic and functional results in a surgical stage. The absence of guidelines to treat dentulous areas is often due to a lack of computer-assisted surgery. The authors have attempted to use this surgical methodology to replace residual teeth with an immediate implantoprosthetic restoration. The aim of this case report is to show the possibility of treating a dentulous patient by applying a computer-assisted surgical protocol associated with the use of a double surgical template: one before extraction and a second one after extraction of selected teeth.