Leukocyte and bacteria imaging in prosthetic joint infection

There has been a significant increase in the number of joint prosthesis replacements worldwide. Although relatively uncommon, complications can occur with the most serious being an infection. Various radiological and nuclear imaging techniques are available to diagnose prosthetic joint infections (PJI). In this review article, we describe the pathophysiology of PJI, the principles of nuclear medicine imaging and the differences between Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET). The value of nuclear medicine techniques for clinical practice is also discussed.Then we provide an overview of the most often used radionuclide imaging techniques that may be helpful in diagnosing prosthetic joint infection: the 67Ga-citrate, labelled white blood cells in vitro and in vivo (monoclonal antibodies directed against specific targets on the leukocytes), and 18F-fluorodeoxyglucose (18F-FDG). We describe their working methods, the pitfalls, and the interpretation criteria. Furthermore, we review recent advances in imaging bacteria, a molecular imaging method that holds promises for the detection of occult infections. We conclude proposing two diagnostic flow-charts, based on data in the literature, that could help the clinicians to choose the best nuclear imaging method when they have a patient with suspicion of or with proven PJI

Advances in targeted Alpha therapy for prostate cancer

BACKGROUND: Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. DESIGN: In this review, we discuss the history, progress, and future potential of TαT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. RESULTS: A clinical proof of concept that TαT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TαT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TαTs with other agents, including chemotherapy, androgen receptor (AR)-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TαTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. CONCLUSIONS: The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TαT trial development suggest that TαT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TαT in prostate cancer treatment

Inner horizon instability and the unstable cores of regular black holes

Regular black holes with nonsingular cores have been considered in several approaches to quantum gravity, and as agnostic frameworks to address the singularity problem and Hawking’s information paradox. While in a recent work we argued that the inner core is destabilized by linear perturbations, opposite claims were raised that regular black holes have in fact stable cores. To reconcile these arguments, we discuss a generalization of the geometrical framework, originally applied to Reissner-Nordtsröm black holes by Ori, and show that regular black holes have an exponentially growing Misner-Sharp mass at the inner horizon. This result can be taken as an indication that stable nonsingular black hole spacetimes are not the definitive endpoint of a quantum gravity regularization mechanism, and that nonperturbative backreation effects must be taken into account in order to provide a consistent description of the quantum-gravitational endpoint of gravitational stellar collapse

On the Inner Horizon Instability of Non-Singular Black Holes

Regular black holes represent a conservative model in which the classical singularity is replaced by a non-singular core without necessarily modifying the spacetime outside the trapping horizon. Given the possible lack of phenomenological signatures, it is crucial to study the consistency of the model. In this short work, we review the physical mechanism leading to the instability of the central core, arguing that that non-perturbative backreation is non-negligible and must be taken into account to provide a meaningful description of physical black holes

Laparoscopic distal pancreatectomy in Italy: A systematic review and meta-analysis

Background The use of laparoscopic distal pancreatectomy (LDP) increased in the past twenty years but the real diffusion of this technique is still unknown as well as the type of centers (high or low volume) in which this procedure is more frequently performed. Data Source A systematic review was performed to evaluate the frequency of LDP in Italy and to compare indications and results in high volume centers (HVCs) and in low volume centers (LVCs). Results From 95 potentially relevant citations identified, only 5 studies were included. A total of 125 subjects were analyzed, of whom 95 (76.0%) were from HVCs and 30 (24.0%) from LVCs. The mean number of LDPs performed per year was 6.5. The mean number of patients who underwent LDP per year was 8.8 in HVCs and 3.0 in LVCs (P<0.001). The most frequent lesions operated on in HVCs were cystic tumors (62.1%, P<0.001) while, in LVCs, solid neoplasms (76.7%, P<0.001). In HVCs, malignant neoplasms were treated with LDP less frequently than in LVCs (17.9% vs 50.0%, P<0.001). Splenectomy was performed for non-oncologic reason frequenter in HVCs than in LVCs (70.2% vs 25.0%, P=0.004). The length of stay was shorter in HVCs than in LVCs (7.5 vs 11.3, P<0.001). No differences were found regarding age, gender, ductal adenocarcinoma treated, operative time, conversion, morbidity, postoperative pancreatic fistula, reoperation and margin status. Conclusions LDPs were frequently performed in Italy. The "HVC approach" is characterized by a careful selection of patients undergoing LDP. The "LVC approach" is based on the hypothesis that LDPs are equivalent both in short-term and long-term results to laparotomic approach. These data are not conclusive and they point out the need for a national register of laparoscopic pancreatectomy

In silico validation of MCID tool for voxel dosimetry applied to 90Y radioembolization of liver malignancies

The aim of this work is validating the Monte Carlo Internal Dosimetry (MCID) tool for internal dosimetry, which allows personalized treatment planning starting from patient-specific images and direct Monte Carlo (MC) simulations. The absorbed dose for different computational phantoms, calculated with MC and with conventional MIRD methods at both organ and voxel level, were compared, obtaining differences of about 0.3% and within 3%, respectively, whereas differences increased (up to 14%) introducing tissue heterogeneities in phantoms. The absorbed dose of spheres with different radius (10 mm ≤ r ≤ 30 mm), calculated from MC code and from OLINDA/EXM was also compared, obtaining differences varying in the range 2–9% after correcting for partial volume effects (PVEs) from imaging. This work validated the MCID tool which allows the fast generation of input macros for MC simulations, starting from patient-specific images. It also shows the impact of tissue inhomogeneities on dosimetric results and their relevance for an accurate dosimetric plan

Ion diffusion modelling of Fricke-agarose dosemeter gels

In Fricke-agarose gels, an accurate determination of the spatial dose distribution is hindered by the diffusion of ferric ions. In this work, a model was developed to describe the diffusion process within gel samples of finite length and, thus, permit the reconstruction of the initial spatial distribution of the ferric ions. The temporal evolution of the ion concentration as a function of the initial concentration is derived by solving Fick's second law of diffusion in two dimensions with boundary reflections. The model was applied to magnetic resonance imaging data acquired at high spatial resolution (0.3 mm) and was found to describe accurately the observed diffusion effect

Natural and CVD type diamond detectors as dosimeters in hadrontherapy applications

Abstract Diamond is potentially a suitable material for use as radiation dosimeter; the wide band gap results in low dark currents and low sensitivity to visible light, the high carrier mobility can give rapid response, the very high density of strong bonds in the crystal structure make diamond very resistent to radiation damage; moreover it is tissue equivalent. The more recent advances in the synthesis of polycrystalline diamond by chemical vapour deposition (CVD) techniques have allowed the synthesis of material with electronic properties suitable for dosimetric application. In this paper we will report the results obtained in the study of the response of a natural diamond dosimeter and a CVD one irradiated with 62 AMeV proton beams to demonstrate their possible application in protontherapy

Immunoscintigraphy for Therapy Decision Making and Follow-Up of Biological Therapies

With the availability of new biological therapies there is the need of more accurate diagnostic tools to non-invasively assess the presence of their targets. In this scenario nuclear medicine offers many radiopharmaceuticals for SPECT or PET imaging of many pathological conditions. The availability of monoclonal antibodies provides tools to target specific antigens involved in angiogenesis, cell cycle or modulation of the immune systems. The radiolabelling of such therapeutic mAbs is a promising method to evaluate the antigenic status of each cancer lesion or inflamed sites before starting the therapy. It may also allow to perform follow-up of such biological therapies. In the present review we provide an overview of the most studied radiolabelled antibodies for therapy decision making and follow-up of patients affected by cancer and other pathological conditions