Experimental validation of an innovative approach in biokinetics study for personalised dosimetry of molecular radiation therapy treatments.

One of today's main challenges in molecular radiation therapy is to assess an individual dosimetry that allows treatment to be tailored to the specific patient, in accordance with the current paradigm of 'personalized medicine'. The evaluation of the absorbed doses for tumor and organs at risk in molecular radiotherapy is typically based on MIRD schema acquiring few experimental points for the assessement of biokinetic parameters. WIDMApp, the wearable individual dose monitoring apparatus, is an innovative approach for internal dosimetry based on a wearable radiation detecting system for individual biokinetics sampling, a Monte Carlo simulation for particle interaction, and an unfolding algorithm for data analysis and integrated activity determination at organ level.

Personalized Dosimetry in the Context of Radioiodine Therapy for Differentiated Thyroid Cancer.

The most frequent thyroid cancer is Differentiated Thyroid Cancer (DTC) representing more than 95% of cases. A suitable choice for the treatment of DTC is the systemic administration of 131-sodium or potassium iodide. It is an effective tool used for the irradiation of thyroid remnants, microscopic DTC, other nonresectable or incompletely resectable DTC, or all the cited purposes.

Yttrium-90 Radioembolization of Colorectal Cancer Liver Metastases: A Systematic Review of Clinical Evidence.

The present work aims to review the clinical evidence of survival outcome after treatment of colorectal cancer liver metastases using yttrium-90 radioembolization, existence, and relevance of clinical, imaging, and genomic predictors of treatment efficacy and the amount of administered activity. Publications listed in PubMed between July 2016 and May 2021 were screened. Predictors of overall survival were reported and distinguished in clinical, imaging, and genomic variables.

Deep Seated Tumour Treatments With Electrons of High Energy Delivered at FLASH Rates: The Example of Prostate Cancer.

Different therapies are adopted for the treatment of deep seated tumours in combination or as an alternative to surgical removal or chemotherapy: radiotherapy with photons (RT), particle therapy (PT) with protons or even heavier ions like C, are now available in clinical centres. In addition to these irradiation modalities, the use of Very High Energy Electron (VHEE) beams (100-200 MeV) has been suggested in the past, but the diffusion of that technique was delayed due to the needed space and budget, with respect to standard photon devices. These disadvantages were not paired by an increased therapeutic efficacy, at least when comparing to proton or carbon ion beams.

Technical note: A wearable radiation measurement system for collection of patient-specific time-activity data in radiopharmaceutical therapy: system design and Monte Carlo simulation results.

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.

Dosimetric optimization of nuclear medicine therapy based on the Council Directive 2013/59/EURATOM and the Italian law N. 101/2020. Position paper and recommendations by the Italian National Associations of Medical Physics (AIFM) and Nuclear Medicine (AIMN).

This recommendation by the Italian Associations of Nuclear Medicine (AIMN) and Medical Physics (AIFM) focuses on the dosimetric optimization of Nuclear Medicine Therapy (NMT) as clearly requested by the article 56 of the EURATOM Directive 2013/59 and its consequent implementation in article 158 in the Italian Law n. 101/2020. However, this statement must deal with scientific and methodological limits that still exist and, above all, with the currently available limited resources.

Diagnostic Value of the Early Heart-to-Mediastinum Count Ratio in Cardiac 123I-mIBG Imaging for Parkinson's Disease.

Background: Early diagnosis of Parkinson's disease (PD) is of primary importance. The delayed (3-4 h after injection) Iodine-123-Metaiodobenzylguanidine (123I-mIBG) scintigraphy has been proven to be effective in early differential diagnosis for Lewy body disease. But early imaging (15-30 min after injection) has only been marginally studied for its possible diagnostic role.

PET-CT post therapy dosimetry in radioembolization with resin Y microspheres: Comparison with pre-treatment SPECT-CT Tc-MAA results.

Resin microspheres radioembolization is an effective treatment for liver tumors when the surgical option is not feasible. Doses delivered to tumor and normal liver can be assess in the pre-therapy phase by means of a Tc-MAA SPECT-CT simulation and after the treatment with Y PET-CT acquisition. The optimal therapeutic Y activity is determined on Tc-MAA SPECT-CT dose results in order to avoid healthy parenchyma toxicity and to effectively irradiate the tumor.

Advances in targeted alpha therapy for prostate cancer.

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. 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. 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.

Central Venous Stenosis after Hemodialysis: Case Reports and Relationships to Catheters and Cardiac Implantable Devices.

The appropriate vascular access for hemodialysis in patients with cardiac implantable electronic devices (CIED) is undefined. We describe two cases of end-stage renal disease patients with CIED and tunneled central venous catheter (CVC) who developed venous cava stenosis: (1) a 70-year-old man with sinus node disease and pacemaker in 2013, CVC, and a Brescia-Cimino forearm fistula in 2015; (2) a 75-year-old woman with previous ventricular arrhythmia with implanted defibrillator in 2014 and CVC in 2016. In either case, after about 1 year from CVC insertion, patients developed superior vena cava (SVC) syndrome due to stenosis diagnosed by axial computerized tomography.

T1 and extracellular volume fraction mapping in cardiac magnetic resonance: estimation of accuracy and precision of a novel algorithm.

Magnetic resonance imaging is effective for non-invasive detection of myocardial diseases by extracellular volume fraction (ECV) estimation. A new methodology for T1 and ECV mapping is tested in this work, comparing results with other well-consolidated methods. The associated level of uncertainty for data was also estimated, to assess the reliability of the technique.

Correlation of dose with toxicity and tumour response to Y- and Lu-PRRT provides the basis for optimization through individualized treatment planning.

Purpose: Peptide receptor radionuclide therapy (PRRT) with Y-labelled and Lu-labelled peptides is an effective strategy for the treatment of metastatic/nonresectable neuroendocrine tumours (NETs). Dosimetry provides important information useful for optimizing PRRT with individualized regimens to reduce toxicity and increase tumour responses. However, this strategy is not applied in routine clinical practice, despite the fact that several dosimetric studies have demonstrated significant dose-effect correlations for normal organ toxicity and tumour response that can better guide therapy planning.

New SPECT and PET Radiopharmaceuticals for Imaging Inflammatory Diseases: A Meta-analysis of the Last 10 Years.

Modern molecular nuclear medicine is rapidly developing in the field of imaging of chronic inflammatory diseases, and many new radiopharmaceuticals have been recently described and tested in animals and man. These can detect early pathophysiological changes before the development of anatomical changes and, often, before clinical onset of symptoms. This field includes new radiopharmaceuticals for SPECT and PET use to define new strategies for imaging immune cells as well as tissue modifications induced by the inflammatory process.

Dosimetry-Based Consideration on Remission and Relapse after Therapy with Ra-Dichloride in Castration-Resistant Prostate Cancer (CRPC) with Bone Metastases. A Case Report.

Here, we present the case of a 64-year-old male patient diagnosed with castration-resistant prostate cancer (CRPC) with bone metastasis, treated with abiraterone prednisone/prednisolone in combination with Ra-dichloride therapy, who had remission and a subsequent relapse of bone metastasis on repeated bone scans after therapy. We also discuss the possibility of continuing the Ra-dichloride therapy over the six planned administrations by administering other cycles at the same dose or at higher doses, if shown to be devoid of a significant increase in side effects, based on dosimetry considerations.

[Hyperuricaemia and Chronic Kidney Disease].

Hyperuricemia is defined as serum uric acid values greater than 6 mg/dl and could occur either due to hyperproduction or as a result of reduced renal excretion, which exceeds gut compensation. In Italy, prevalence is around 12% of the general population and increases in renal disease up to 60%. Recent experimental studies demonstrated a role of uric acid in the development of arterial hypertension and systemic arteriosclerosis, with an increase in cardiovascular risk.

Current Status of Molecular Imaging in Inflammatory and Autoimmune Disorders.

In the field of inflammation imaging, nuclear medicine techniques can be considered as a non-invasive tool to early detect pathophysiological changes in affected tissues. These changes usually occur before clinical onset of symptoms and before the development of anatomical changes, that are commonly detected by radiological procedures. This is particularly important for prognostic purposes, therapy decision making and for therapy follow-up.

Impact of missing attenuation and scatter corrections on Tc-MAA SPECT 3D dosimetry for liver radioembolization using the patient relative calibration methodology: A retrospective investigation on clinical images.

Purpose: To investigate the clinical implication of performing pre-treatment dosimetry for Y-microspheres liver radioembolization on Tc-MAA SPECT images reconstructed without attenuation or scatter correction and quantified with the patient relative calibration methodology.

Methods: Twenty-five patients treated with SIR-Spheres at Istituto Europeo di Oncologia and 31 patients treated with TheraSphere at Istituto Nazionale Tumori were considered. For each acquired Tc-MAA SPECT, four reconstructions were performed: with attenuation and scatter correction (AC_SC), only attenuation (AC_NoSC), only scatter (NoAC_SC) and without corrections (NoAC_NoSC).

High-flow arteriovenous fistula and heart failure: could the indexation of blood flow rate and echocardiography have a role in the identification of patients at higher risk?

Background: Although only high-flow arteriovenous fistulas (AVFs) are postulated to cause high-output cardiac failure (HOCF), there are currently no universally accepted criteria defining a high-flow fistula.

Methods: To verify if vascular access blood flow (Qa) ≥ 2000 ml/min provides an accurate definition of high-flow fistula, we selected 29 consecutive patients with Qa ≥ 2000 ml/min at color-duplex ultrasound examination and assessed them for the presence of cardiac failure symptoms; transthoracic echocardiography was also performed.

Results: Nineteen patients (65%) had heart failure symptoms and were classified with HOCF.

A 3-variable prognostic score (3-PS) for overall survival prediction in metastatic castration-resistant prostate cancer treated with Radium-dichloride.

Objective: In mCRPC patients treated with Ra, a major issue is the validation of reliable prognostic and predictive biomarkers to maximize clinical benefit and minimize toxicities and costs. Bearing in mind how changes in tALP did not meet statistical requirements as surrogate marker for survival, aim of this single-center retrospective study was to characterize the prognostic and predictive role of baseline clinical variables associated with overall survival in patients receiving Ra treatment.

Methods: 92 consecutive CRPC patients with symptomatic bone metastases receiving Ra treatment were included.

Myocardial blood flow estimates from dynamic contrast-enhanced magnetic resonance imaging: three quantitative methods.

Dynamic contrast-enhanced cardiovascular magnetic resonance imaging can be used to quantitatively assess the myocardial blood flow (MBF), recovering the tissue impulse response function for the transit of a gadolinium bolus through the myocardium. Several deconvolution techniques are available, using various models for the impulse response. The method of choice may influence the results, producing differences that have not been deeply investigated yet.

Gamma camera calibrations for the Italian multicentre study for lesion dosimetry in Ra therapy of bone metastases.

Purpose: The aim was to calibrate gamma cameras in the framework of the Italian multicentre study for lesion dosimetry in Ra therapy of bone metastases. Equipments of several manufacturers and different models were used.

Methods: Eleven gamma cameras (3/8- and 5/8-inch crystal) were used, acquiring planar static images with double-peak (82 and 154keV, 20% wide) and MEGP collimator.

The Italian multicentre dosimetric study for lesion dosimetry in Ra therapy of bone metastases: Calibration protocol of gamma cameras and patient eligibility criteria.

Purpose: The aims of this work were to explore patient eligibility criteria for dosimetric studies in Ra therapy and evaluate the effects of differences in gamma camera calibration procedures into activity quantification.

Methods: Calibrations with Ra were performed with four gamma cameras (3/8-inch crystal) acquiring planar static images with double-peak (82 and 154keV, 20% wide) and MEGP collimator. The sensitivity was measured in air by varying activity, source-detector distance, and source diameter.

Impact of SPECT corrections on 3D-dosimetry for liver transarterial radioembolization using the patient relative calibration methodology.

Purpose: Many centers aim to plan liver transarterial radioembolization (TARE) with dosimetry, even without CT-based attenuation correction (AC), or with unoptimized scatter correction (SC) methods. This work investigates the impact of presence vs absence of such corrections, and limited spatial resolution, on 3D dosimetry for TARE.

Methods: Three voxelized phantoms were derived from CT images of real patients with different body sizes.

Nephroprotection with saxagliptin.

The nephroprotective effect of the new anti-diabetic drugs acting on incretin system is suggested by preclinical studies. However, no study evaluating kidney effects of these drugs as primary outcome on the long term has been conducted in patients followed in diabetes centers. We designed a pilot observational study involving two diabetes clinics to evaluate the effect of prolonged treatment with saxagliptin on renal function in type 2 diabetics.

A case report of image-based dosimetry of bone metastases with Alpharadin ((223)Ra-dichloride) therapy: inter-fraction variability of absorbed dose and follow-up.

A 70-year-old man affected by bone metastases from castration resistant prostate cancer underwent Alpharadin ((223)Ra-dichloride) therapy (6 administrations of 50 kBq per kg i.v., once every 4 weeks).