The possibility to use β
decaying isotopes for radioguided surgery (RGS) has been recently proposed, and first promising tests on ex-vivo samples of Meningioma and intestinal Neuroendocrine Tumor ...(NET) have been published. This paper reports a study of the uptake of
Ga-DOTATOC in pancreatic NETs (pNETs) in order to assess the feasibility of a new RGS approach using
Y-DOTATOC. Tumor and healthy pancreas uptakes were estimated from
Ga-DOTATOC PET/CT scans of 30 patients with pNETs. From the obtained SUVs (Standardised Uptake Value) and TNRs (Tumor Non tumor Ratio), an analysis algorithm relying on a Monte Carlo simulation of the detector has been applied to evaluate the performances of the proposed technique. Almost all considered patients resulted to be compatible with the application of β
-RGS assuming to administer 1.5 MBq/kg of activity of
Y-DOTATOC 24 h before surgery, and a sampling time of few seconds. In just 2 cases the technique would have required a mildly increased amount of activity or of sampling time. Despite a high physiological uptake of
Ga-DOTATOC in the healthy pancreas, the proposed RGS technique promises to be effective. This approach allows RGS to find application also in pancreatic diseases, where traditional techniques are not viable.
In the last decade, many innovative nanodrugs have been developed, as well as many nanoradiocompounds that show amazing features in nuclear imaging and/or radiometabolic therapy. Their potential uses ...offer a wide range of possibilities. It can be possible to develop nondimensional systems of existing radiopharmaceuticals or build engineered systems that combine a nanoparticle with the radiopharmaceutical, a tracer, and a target molecule, and still develop selective nanodetection systems. This review focuses on recent advances regarding the use of gold nanoparticles and nanorods in nuclear medicine. The up-to-date advancements will be shown concerning preparations with special attention on the dimensions and functionalizations that are most used to attain an enhanced performance of gold engineered nanomaterials. Many ideas are offered regarding recent in vitro and in vivo studies. Finally, the recent clinical trials and applications are discussed.
Background
Recently, a flexible DROP-IN gamma-probe was introduced for robot-assisted radioguided surgery, using traditional low-energy SPECT-isotopes. In parallel, a novel approach to achieve ...sensitive radioguidance using beta-emitting PET isotopes has been proposed. Integration of these two concepts would allow to exploit the use of PET tracers during robot-assisted tumor-receptor-targeted. In this study, we have engineered and validated the performance of a novel DROP-IN beta particle (DROP-IN
β
) detector.
Methods
Seven prostate cancer patients with PSMA-PET positive tumors received an additional intraoperative injection of ~ 70 MBq
68
Ga-PSMA-11, followed by robot-assisted prostatectomy and extended pelvic lymph node dissection. The surgical specimens from these procedures were used to validate the performance of our DROP-IN
β
probe prototype, which merged a scintillating detector with a housing optimized for a 12-mm trocar and prograsp instruments.
Results
After optimization of the detector and probe housing via Monte Carlo simulations, the resulting DROP-IN
β
probe prototype was tested in a robotic setting. In the ex vivo setting, the probe—positioned by the robot—was able to identify
68
Ga-PSMA-11 containing hot-spots in the surgical specimens: signal-to-background (S/B) was > 5 when pathology confirmed that the tumor was located < 1 mm below the specimen surface.
68
Ga-PSMA-11 containing (and PET positive) lymph nodes, as found in two patients, were also confirmed with the DROP-IN
β
probe (S/B > 3). The rotational freedom of the DROP-IN design and the ability to manipulate the probe with the prograsp tool allowed the surgeon to perform autonomous beta-tracing.
Conclusions
This study demonstrates the feasibility of beta-radioguided surgery in a robotic context by means of a DROP-IN
β
detector. When translated to an in vivo setting in the future, this technique could provide a valuable tool in detecting tumor remnants on the prostate surface and in confirmation of PSMA-PET positive lymph nodes.
The aim was the validation of a platform for internal dosimetry, named MCID, based on patient-specific images and direct Monte Carlo (MC) simulations, for radioembolization of liver tumors with ...90Y-labeled microspheres. CT of real patients were used to create voxelized phantoms with different density and activity maps. SPECT acquisitions were simulated by the SIMIND MC code. Input macros for the GATE/Geant4 code were generated by MCID, loading coregistered morphological and functional images and performing image segmentation. The dosimetric results obtained from the direct MC simulations and from conventional MIRD approach at both organ and voxel level, in condition of homogeneous tissues, were compared, obtaining differences of about 0.3% and within 3%, respectively, whereas differences increased (up to 14%) introducing tissue heterogeneities in phantoms. Mean absorbed dose for spherical regions of different sizes (10 mm ≤ r ≤ 30 mm) from MC code and from OLINDA/EXM were also compared obtaining differences varying in the range 7–69%, which decreased to 2–9% after correcting for partial volume effects (PVEs) from imaging, confirming that differences were mostly due to PVEs, even though a still high difference for the smallest sphere suggested possible source description mismatching. This study validated the MCID platform, which allows the fast implementation of a patient-specific GATE simulation, avoiding complex and time-consuming manual coding. It also points out the relevance of personalized dosimetry, accounting for inhomogeneities, in order to avoid absorbed dose misestimations.
The interaction of the incoming beam radiation with the patient body in hadrontherapy treatments produces secondary charged and neutral particles, whose detection can be used for monitoring purposes ...and to perform an on-line check of beam particle range. In the context of ion-therapy with active scanning, charged particles are potentially attractive since they can be easily tracked with a high efficiency, in presence of a relatively low background contamination. In order to verify the possibility of exploiting this approach for in-beam monitoring in ion-therapy, and to guide the design of specific detectors, both simulations and experimental tests are being performed with ion beams impinging on simple homogeneous tissue-like targets (PMMA). From these studies, a resolution of the order of few millimeters on the single track has been proven to be sufficient to exploit charged particle tracking for monitoring purposes, preserving the precision achievable on longitudinal shape. The results obtained so far show that the measurement of charged particles can be successfully implemented in a technology capable of monitoring both the dose profile and the position of the Bragg peak inside the target and finally lead to the design of a novel profile detector. Crucial aspects to be considered are the detector positioning, to be optimized in order to maximize the available statistics, and the capability of accounting for the multiple scattering interactions undergone by the charged fragments along their exit path from the patient body. The experimental results collected up to now are also valuable for the validation of Monte Carlo simulation software tools and their implementation in Treatment Planning Software packages.
Acrylates-based co-polymeric nanoparticles (PNPs) are widely used in nanomedicine applications due to their tunable hydrophilic surface, physical and chemical versatility. Particularly attracting is ...their use as nanocarriers for imaging agents. Herein, methyl methacrylate (MMA) and N,N-dimethylacrylamide (DMAA) monomers were used to synthesize hydrophilic p(MMA-co-DMAA) nanoparticles in the 200–600 nm size range via surfactant-free radical emulsion polymerization technique. Different MMA/DMAA molar ratios, temperatures, and reaction times were investigated to evaluate their role in determining the average particle size, polydispersity, and optimizing surface properties of PNPs. Nanoparticles formation, stability (in water and culture medium for cell growth), swelling behavior, structural features and molecular weights were assessed by spectroscopic, non-spectroscopic, and chromatographic techniques. Morphological profiles confirming spherical-shaped NPs were obtained at solid state via microscopies (FESEM, AFM). To use such colloids as potential imaging agents, PNPs were loaded with Y3+(aq) ions by the addition of aqueous solutions of YCl3 at different concentrations, and results compared with p(MMA-co-AA)-DTPA NPs (AA = acrylic acid) functionalized with DTPA chelating agent. Yttrium ions loading percentage was ca. 90% for both p(MMA-co-DMAA) and p(MMA-co-AA)-DTPA, with negligible release (<15%) over a month. Parallelly, optical imaging nanoprobes were obtained by physical encapsulation of fluorescein isothiocyanate isomer I (FITC) dye during the synthesis process, and the spontaneous FITC incorporation was evaluated by spectroscopic studies and fluorescence microscopy. Cytotoxicity studies on pristine and yttrium-loaded nanoparticles were done in vitro on human glioblastoma T98G cell line within 24 h of treatment. Transmission electron microscopy (TEM) studies on cancer cells treated with NPs confirmed an active uptake of PNPs through multiple endocytic pathways to reach the perinuclear region of the cell. Overall, this work elucidated the role of synthetic parameters for a rational design of hydrophilic PNPs as nanocarriers for imaging agents with potential applications in theranostics.
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•Acrylates-based polymeric nanobeads are synthesized via surfactant-free radical emulsion polymerization.•Structure and morphology are evaluated by different characterization techniques.•Surface Y3 + (aq) ions loading and release is studied.•In situ FITC dye is encapsulated inside nanoparticles core to obtain fluorescent nanoparticles.•The in vitro studies on T98G cells show absence of cytotoxicity within 24 h.
Purpose: A high level of personalization in Molecular Radiotherapy (MRT) could bring advantages in terms of treatment effectiveness and toxicity reduction. Individual organ‐level dosimetry is crucial ...to describe the radiopharmaceutical biodistribution expressed by the patient, to estimate absorbed doses to normal organs and target tissue(s). This paper presents a proof‐of‐concept Monte Carlo simulation study of “WIDMApp” (Wearable Individual Dose Monitoring Apparatus), a multi‐channel radiation detector and data processing system for in vivo patient measurement and collection of radiopharmaceutical biokinetic data (i.e., time‐activity data). Potentially, such a system can increase the amount of such data that can be collected while reducing the need to derive it via nuclear medicine imaging.
Methods: a male anthropomorphic MIRD phantom was used to simulate photons (i.e., gamma‐rays) propagation in a patient undergoing a 131I thyroid treatment. The administered activity was set to the amount usually administered for the treatment of differentiated carcinoma while its initial distribution in different organs was assigned following the ICRP indications for the 131I biokinetics. Using this information, the simulation computes the Time‐dependent Counts Curves (TCCs) that would have been measured by seven WIDMApp‐like sensors placed and oriented to face each one of five emitting organs plus two thyroid lobes. A deconvolution algorithm was then applied on this simulated data set to reconstruct the Time‐Activity Curve (TAC) of each organ. Deviations of the reconstructed TACs parameters from values used to generate them were studied as a function of the deconvolution algorithm initialization parameters and assuming non‐Poisson fluctuation of the TCCs data points.
Results: This study demonstrates that it is possible, at least in the simple simulated scenario, to reconstruct the organ cumulated activity by measuring the time dependence of counts recorded by several detectors placed at selected positions on the patient's body. The ability to perform in vivo sampling more frequently than conventional biokinetic studies increases the number of time points and therefore the accuracy in TAC estimates. In this study, an accuracy on cumulated activity of 5% is obtained even with a 20% error on the TCC data points and a 50% error on the initial guess on the parameters of the deconvolution algorithm.
Conclusions: the WIDMApp approach could provide an effective tool to characterize more accurately the radiopharmaceutical biokinetics in MRT patients, reducing the need of resources of nuclear medicine departments, such as technologist and scanner time, to perform individualized biokinetics studies. The relatively simple hardware for the approach proposed would allow its application to large numbers of patients. The results obtained justify development of an actual prototype system to characterize this technique under realistic conditions.
The Symposium DISCRETE2010 on Prospects in the Physics of Discrete Symmetries was held at the Sapienza Universitàa di Roma, Italy from 6–11 December 2010. This second edition, after the successful ...one in Valencia in 2008, covered all theoretical and experimental progress in the field, and aimed at a thorough discussion on the latest developments. The topics covered included: T, C, P, CP symmetries; accidental symmetries (B, L conservation); CPT symmetry, decoherence, Lorentz symmetry breaking; neutrino mass and mixing; cosmology and astroparticles, dark matter searches; experimental prospects at LHC, Super flavor factories, and new facilities. The Symposium was organized in plenary sessions with a total of 23 invited talks, and parallel sessions with a total of 80 talks including both invited and selected contributions from the submitted abstracts. The speakers of the plenary sessions were: Achille Stocchi, Andreas Weiler, Kevin Pitts, Tim Gershon, Marco Sozzi, Neal Weiner, Vasiliki Mitsou, Bernard Sadoulet, Gianfranco Bertone, J. Eric Grove, Mauro Mezzetto, Alexei Yu Smirnov, Oliviero Cremonesi, Antonio Riotto, Reno Mandolesi, Brett Altschul, Jose Bernabeu, Lawrence Hall, Marco Grassi, Yannis K. Semertzidis, Riccardo Barbieri, Gigi Rolandi, Luciano Maiani. The Symposium venue was the CNR (Consiglio Nazionale delle Ricerche) headquarter building, close to the Sapienza University. At the end of the Symposium a special open session, devoted to a wider audience, was held at the Pontifical University of the Holy Cross, in the historical center of Rome. The symposium was attended by about 140 participants, about half coming from Italy, and the rest mainly from other European countries and United States. Among the social events was a concert at the Aula Magna of the Sapienza University, and a social dinner in the historical Palazzo Pallavicini-Rospigliosi on the Quirinale Hill. The next symposium of the series will be organised by IST, Universidade Tàecnica de Lisboa, Portugal, from 3 to 7 December 2012. Roma, November 2011 The Editors Antonio Di Domenico Cesare Bini Caterina Bloise Fabio Bossi Riccardo Faccini Paolo Gauzzi Gino Isidori Paolo Lipari Lucio Ludovici Luca Silvestrini The PDF file also contains committee, secretariat, sponsor and participant lists, plus the conference poster and photograph.
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