Gold nanoparticles meet medical radionuclides

Thanks to their unique optical and physicochemical properties, gold nanoparticles have gained increased interest as radiosensitizing, photothermal therapy and optical imaging agents to enhance the effectiveness of cancer detection and therapy. Furthermore, their ability to carry multiple medically relevant radionuclides broadens their use to nuclear medicine SPECT and PET imaging as well as targeted radionuclide therapy. In this review, we discuss the radiolabeling process of gold nanoparticles and their use in (multimodal) nuclear medicine imaging to better understand their specific distribution, uptake and retention in different in vivo cancer models. In addition, radiolabeled gold nanoparticles enable image-guided therapy is reviewed aswell as the enhancement of targeted radionuclide therapy and nanobrachytherapy through an increased dose deposition and radiosensitization, as demonstrated by multiple Monte Carlo studies and experimental in vitro and in vivo studies. (C) 2021 The Authors. Published by Elsevier Inc

Gold nanoparticles affect the antioxidant status in selected normal human cells

Purpose: This study evaluates the cytotoxicity of AuNPs coated with polyallylamine (AuNPs-PAA) and conjugated or not to the epidermal growth factor receptor (EGFR)-targeting antibody Cetuximab (AuNPs-PAA-Ctxb) in normal human kidney (HK-2), liver (THLE-2) and microvascular endothelial (TIME) cells, and compares it with two cancer cell lines that are EGFR-overexpressing (A431) or EGFR-negative (MDA-MB-453). Results: Conjugation of Cetuximab to AuNPs-PAA increased the AuNPs-PAA-Ctxb interactions with cells, but reduced their cytotoxicity. TIME cells exhibited the strongest reduction in viability after exposure to AuNPs-PAA(±Ctxb), followed by THLE-2, MDA-MB-453, HK-2 and A431 cells. This cell type-dependent sensitivity was strongly correlated to the inhibition of thioredoxin reductase (TrxR) and glutathione reductase (GR), and to the depolarization of the mitochondrial membrane potential. Both are suggested to initiate apoptosis, which was indeed detected in a concentration- and time-dependent manner. The role of oxidative stress in AuNPs-PAA(±Ctxb)-induced cytotoxicity was demonstrated by co-incubation of the cells with N-acetyl L-cysteine (NAC), which significantly decreased apoptosis and mitochondrial membrane depolarization. Conclusion: This study helps to identify the cells and tissues that could be sensitive to AuNPs and deepens the understanding of the risks associated with the use of AuNPs in vivo.status: publishe

Hybrid gold nanoparticles coated with organic polymers and antibodies as platform for cancer theranostics: Cytotoxicity assessment

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Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [153^{153}Sm]Sm-DOTA-TATE

Samarium-153 is a promising theranostic radionuclide, but low molar activities (Am) resulting from its current production route render it unsuitable for targeted radionuclide therapy (TRNT). Recent efforts combining neutron activation of $^{152}$Sm in the SCK CEN BR2 reactor with mass separation at CERN/MEDICIS yielded high-Am $^{153}$Sm. In this proof-of-concept study, we further evaluated the potential of high-Am $^{153}$Sm for TRNT by radiolabeling to DOTA-TATE, a well-established carrier molecule binding the somatostatin receptor 2 (SSTR2) that is highly expressed in gastroenteropancreatic neuroendocrine tumors. DOTA-TATE was labeled with $^{153}$Sm and remained stable up to 7 days in relevant media. The binding specificity and high internalization rate were validated on SSTR2-expressing CA20948 cells. In vitro biological evaluation showed that [$^{153}$Sm]Sm-DOTA-TATE was able to reduce CA20948 cell viability and clonogenic potential in an activity-dependent manner. Biodistribution studies in healthy and CA20948 xenografted mice revealed that [$^{153}$Sm]Sm-DOTA-TATE was rapidly cleared and profound tumor uptake and retention was observed whilst these were limited in normal tissues. This proof-of-concept study showed the potential of mass-separated $^{153}$Sm for TRNT and could open doors towards wider applications of mass separation in medical isotope production

Radiobiology of Combining Radiotherapy with Other Cancer Treatment Modalities

International audienceAbstract In this chapter, we address the role of radiation as treatment modality in the context of oncological treatments given to patients. Physical aspects of the use of ionizing radiation (IR)—by either photons, neutrons, or charged (high linear energy transfer) particles—and their clinical application are summarized. Information is also provided regarding the radiobiological rationale of the use of conventional fractionation as well as alternative fractionation schedules using deviating total dose, fraction size, number of fractions, and the overall treatment time. Pro- and contra arguments of hypofractionation are discussed. In particular, the biological rationale and clinical application of Stereotactic Body Radiation Therapy (SBRT) are described. Furthermore, background information is given about FLASH radiotherapy (RT), which is an emerging new radiation method using ultra-high dose rate allowing the healthy, normal tissues and organs to be spared while maintaining the antitumor effect. Spatial fractionation of radiation in tumor therapy, another method that reduces damage to normal tissue is presented. Normal tissue doses could also be minimized by interstitial or intraluminal irradiation, i.e., brachytherapy, and herein an overview is given on the principles of brachytherapy and its clinical application. Furthermore, details are provided regarding the principles, clinical application, and limitations of boron neutron capture therapy (BNCT). Another important key issue in cancer therapy is the combination of RT with other treatment modalities, e.g., chemotherapy, targeted therapy, immunotherapy, hyperthermia, and hormonal therapy. Combination treatments are aimed to selectively enhance the effect of radiation in cancer cells or to trigger the immune system but also to minimize adverse effects on normal cells. The biological rationale of all these combination treatments as well as their application in clinical settings are outlined. To selectively reach high concentrations of radionuclides in tumor tissue, radioembolization is a highly interesting approach. Also, radioligand therapy which enables specific targeting of cancer cells, while causing minimal harm surrounding healthy tissues is presented. A brief overview is provided on how nanotechnology could contribute to the diagnosis and treatment of cancer. Last but not least, risk factors involved in acquiring secondary tumors after RT are discussed