The potential of targeted radionuclide therapy to treat hypoxic tumor cells.

Tumor hypoxia contributes to cancer progression and therapy resistance. Several strategies have been investigated to relieve tumor hypoxia, of which some were successful. However, their clinical application remains challenging and therefore they are not used in daily clinical practice.

A framework for in-field and out-of-field patient specific secondary cancer risk estimates from treatment plans using the TOPAS Monte Carlo system.

. To allow the estimation of secondary cancer risks from radiation therapy treatment plans in a comprehensive and user-friendly Monte Carlo (MC) framework..

Towards effective CAIX-targeted radionuclide and checkpoint inhibition combination therapy for advanced clear cell renal cell carcinoma.

Immune checkpoint inhibitors (ICI) are routinely used in advanced clear cell renal cell carcinoma (ccRCC). However, a substantial group of patients does not respond to ICI therapy. Radiation is a promising approach to increase ICI response rates since it can generate anti-tumor immunity.

Effectiveness of staff radiation protection devices for interventional cardiology procedures.

Purpose: To evaluate the effectiveness of currently available radioprotective (RP) devices in reducing the dose to interventional cardiology staff, especially to the eye lens and brain.

Methods: The performances of five RP devices (masks, caps, patient drapes, staff lead and lead-free aprons and Zero-Gravity (ZG) suspended radiation protection system) were assessed by means of Monte Carlo (MC) simulations. A geometry representative of an interventional cardiology setup was modelled and several configurations, including beam projections and staff distance from the source, were investigated.

In vitro dose effect relationships of actinium-225- and lutetium-177-labeled PSMA-I&T.

Purpose: Targeting the prostate-specific membrane antigen (PSMA) using lutetium-177-labeled PSMA-specific tracers has become a very promising novel therapy option for prostate cancer (PCa). The efficacy of this therapy might be further improved by replacing the β-emitting lutetium-177 with the α-emitting actinium-225. Actinium-225 is thought to have a higher therapeutic efficacy due to the high linear energy transfer (LET) of the emitted α-particles, which can increase the amount and complexity of the therapy induced DNA double strand breaks (DSBs).

Therapeutic efficacy of heterogeneously distributed radiolabelled peptides: Influence of radionuclide choice.

Purpose: To model dose-response relationships for in vivo experiments with radiolabelled peptides enabling maximum therapeutic efficacy while limiting toxicity to kidney and bone marrow.

Methods: A multiregional murine kidney phantom, with a kinetic model for cortex and outer medulla distribution, were used to predict renal toxicity. Maximum tolerated activities to avoid nephrotoxicity (at 40 Gy Biological Effective Dose BED) and hematologic toxicity (at 2 Gy) were compared.

Modeling Early Radiation DNA Damage Occurring During Lu-DOTATATE Radionuclide Therapy.

The aim of this study was to build a simulation framework to evaluate the number of DNA double-strand breaks (DSBs) induced by in vitro targeted radionuclide therapy (TRT). This work represents the first step toward exploring underlying biologic mechanisms and the influence of physical and chemical parameters to enable a better response prediction in patients. We used this tool to characterize early DSB induction by Lu-DOTATATE, a commonly used TRT for neuroendocrine tumors.

Dosimetric Evaluation of the Effect of Receptor Heterogeneity on the Therapeutic Efficacy of Peptide Receptor Radionuclide Therapy: Correlation with DNA Damage Induction and In Vivo Survival.

Our rationale was to build a refined dosimetry model for Lu-DOTATATE in vivo experiments enabling the correlation of absorbed dose with double-strand break (DSB) induction and cell death. Somatostatin receptor type 2 expression of NCI-H69 xenografted mice, injected with Lu-DOTATATE, was imaged at 0, 2, 5, and 11 d. This expression was used as input to reconstruct realistic 3-dimensional heterogeneous activity distributions and tissue geometries of both cancer and heathy cells.

Cellular dosimetry of [Lu]Lu-DOTA-[Tyr]octreotate radionuclide therapy: the impact of modeling assumptions on the correlation with in vitro cytotoxicity.

Background: Survival and linear-quadratic model fitting parameters implemented in treatment planning for targeted radionuclide therapy depend on accurate cellular dosimetry. Therefore, we have built a refined cellular dosimetry model for [Lu]Lu-DOTA-[Tyr]octreotate (Lu-DOTATATE) in vitro experiments, accounting for specific cell morphologies and sub-cellular radioactivity distributions.

Methods: Time activity curves were measured and modeled for medium, membrane-bound, and internalized activity fractions over 6 days.

DOSIMETRY DURING PERCUTANEOUS CORONARY INTERVENTIONS OF CHRONIC TOTAL OCCLUSIONS.

Percutaneous coronary interventions (PCI) of coronary chronic total occlusions (CTO) increase the risk of high radiation exposure for both the patient and the cardiologist. This study evaluated the maximum dose to the patients' skin (MSD) and the exposure of the cardiologists during CTO-PCI. Moreover, the efficiency of radioprotective drapes to reduce cardiologist exposure was assessed.

Short stature and body proportion in thalassaemia.

Short stature and short trunk have been reported in thalassaemic patients. We report a study on stature and body proportions in 476 patients (2-36 years old) with beta-thalassaemia major, followed in 12 Italian centres. Auxological data (standing height, sitting height, subischial leg length, target height), haematological data (age at first transfusion, age at start of desferrioxamine [DFX] chelation, mean dose of DFX, ferritin values) and information regarding the presence of endocrine disorders and of bone lesions, were collected and analysed according to the age of the patients, in order to investigate the natural history of the disproportion and the role of siderosis, DFX toxicity and endocrine disorders.

[Concentrations of IgM and IgA in the umbilical cord blood of 400 newborn infants: possible significance and correlations with prenatal infections (preliminary note)].

IgM and IgA dosed in cord sera of 400 infants. IgM are present in all samples; 16.25% of them show levels 25 mg/100 cm3.