Experimental setup for light-to-heat NIR conversion measurements of gold nano-particles\u2019 solutions

In recent years, there is a constantly increasing interest in the application of nanoparticles for cancer diagnosis and cancer therapy. In this respect, the most promising nano-objects at present are the gold nanoparticles. A very convenient and powerful property of these objects is their ability to increase their temperature under electro-magnetic irradiation with certain wavelength. In our research we have directed our efforts toward particular nano-objects specifically sensitive to electromagnetic radiation in the near-infrared region (NIR). In order to study the photothermic properties of the solutions of gold nanoparticles in the NIR we constructed a specific electronic setup consisting of a laser system with interchangeable laser diodes with different wavelength NIR light, a thermally-insulated cuvette-holder compartment with temperature measuring probes and a NIR spectrometer to control the stimulated fluorescence emission of the nanoparticles\u2019 solutions. The temperature measurement compartment with the thermal-insulated cuvette holder was designed to maintain the solutions\u2019 temperature at a fixed value right before the moment of laser irradiation. To maintain the measurement setup at a fixed temperature before the irradiation we used a thermal stabilized system based on two Peltier cells with electronic temperature control. The temperatures of the ambient air and the temperature of the cuvette walls were continuously measured in order to make corrections about the temperature dissipation during the irradiation

New bioconjugated rhenium carbonyls by transmetalation reaction with zinc derivatives

The transmetallation reaction between zinc dithiocarbamates and rhenium carbonyls has been used as a new strategy to link biomolecules to transition metals. The zinc(II) dithiocarbamate of isonipecotic acid (1) and the succinimidyl ester derivative (2) were prepared by straight forward procedures and were fully characterized by spectroscopic and X-ray diffraction methods, showing in both cases the presence of dinuclear complexes. Complex 2 reacted with all the primary and secondary amines studied (glycine methyl ester, β-alanine methyl ester, 1-(2-methoxyphenyl)piperazine and D-(+)-glucosamine) through the activated succinimidyl ester group, linking the metallic fragment with the biomolecule by the formation of a peptidic bond, and leading to the respective bioconjugated zinc complexes 3-6. In all cases, these zinc complexes could be isolated from the reaction medium by simple precipitation. These results evidence the potential of complex 2 to be used as a synthon to link the zinc dithiocarbamate fragment to biomolecules that contain an amine group. Complexes 3-6 were characterized by the usual spectroscopic methods and all data agree with the proposed structures, which do not contain significant interactions between the zinc fragment and the functional groups of these biomolecules. The transmetallation reaction between the zinc complexes 3-6 and the rhenium carbonyl [ReBr₃(CO)₃]²⁻ led to the expected rhenium dithiocarbamates 7-10 with no change in the organic dithiocarbamate fragments, confirming the viability of this reaction as a tool for linking biomolecules to transition elements. All complexes were characterized by spectroscopic methods and the crystal structure of 8 was studied by X-ray diffraction analysis. All data demonstrated that the biomolecule is positioned far away from the fac-{Re(CO)₃} fragment and the octahedral coordination around the metal is completed by the functionalized dithiocarbamate and a phosphine ligand. Finally, the analysis by ESI-MS spectrometry of the reaction between the zinc complex 4 and a water solution of [Re(H₂O)₃(CO)₃]+ at a very low concentration (10 ppm) showed that the transmetallation reaction took place even though the solubility of the zinc complex in water medium was as low as 0.66 ppm. This preliminary result supports the viability of this approach for the preparation of rhenium and technetium target specific radiopharmaceuticals since the preparation of these compounds are always performed in water medium

Development of 177Lu-scFvD2B as a Potential Immunotheranostic Agent for Tumors Overexpressing the Prostate Specific Membrane Antigen

The clinical translation of theranostic 177Lu-radiopharmaceuticals based on inhibitors of the prostate-specific membrane antigen (PSMA) has demonstrated positive clinical responses in patients with advanced prostate cancer (PCa). However, challenges still remain, particularly regarding their pharmacokinetic and dosimetric properties. We developed a potential PSMA-immunotheranostic agent by conjugation of a single-chain variable fragment of the IgGD2B antibody (scFvD2B) to DOTA, to obtain a 177Lu-labelled agent with a better pharmacokinetic profile than those previously reported. The labelled conjugated 177Lu-scFvD2B was obtained in high yield and stability. In vitro, 177Lu-scFvD2B disclosed a higher binding and internalization in LNCaP (PSMA-positive) compared to PC3 (negative control) human PCa cells. In vivo studies in healthy nude mice revealed that 177Lu-scFvD2B present a favorable biokinetic profile, characterized by a rapid clearance from non-target tissues and minimal liver accumulation, but a slow wash-out from kidney. Micro-SPECT/CT imaging of mice bearing pulmonary microtumors evidenced a slow uptake by LNCaP tumors, which steadily rose up to a maximum value of 3.6 SUV at 192 h. This high and prolonged tumor uptake suggests that 177Lu-scFvD2B has great potential in delivering ablative radiation doses to PSMA-expressing tumors, and warrants further studies to evaluate its preclinical therapeutic efficacy

IAEA Contribution to Nanosized Targeted Radiopharmaceuticals for Drug Delivery

The rapidly growing interest in the application of nanoscience in the future design of radiopharmaceuticals and the development of nanosized radiopharmaceuticals in the late 2000 ' s, resulted in the creation of a Coordinated Research Project (CRP) by the International Atomic Energy Agency (IAEA) in 2014. This CRP entitled 'Nanosized delivery systems for radiopharmaceuticals' involved a team of expert scientist from various member states. This team of scientists worked on a number of cutting-edge areas of nanoscience with a focus on developing well-defined, highly effective and site-specific delivery systems of radiopharmaceuticals. Specifically, focus areas of various teams of scientists comprised of the development of nanoparticles (NPs) based on metals, polymers, and gels, and their conjugation/encapsulation or decoration with various tumor avid ligands such as peptides, folates, and small molecule phytochemicals. The research and development efforts also comprised of developing optimum radiolabeling methods of various nano vectors using diagnostic and therapeutic radionuclides including Tc-99m, Ga-68, Lu-177 and Au-198. Concerted efforts of teams of scientists within this CRP has resulted in the development of various protocols and guidelines on delivery systems of nanoradiopharmaceuticals, training of numerous graduate students/post-doctoral fellows and publications in peer reviewed journals while establishing numerous productive scientific networks in various participating member states. Some of the innovative nanoconstructs were chosen for further preclinical applications-all aimed at ultimate clinical translation for treating human cancer patients. This review article summarizes outcomes of this major international scientific endeavor

Optical and Multimodal Peptide-Based Probes For In Vivo Molecular Imaging.

Molecular imaging consists of non-invasive monitoring of spatial-temporal distribution of molecular or cellular processes, and may be used for early disease detection and real-time monitoring of therapeutic responses. Several strategies have been developed over the last two decades. Early attempts used monoclonal antibodies or antibody fragments and, although specific targeting was achieved, these probes was largely unsuccessful. In the quest for better agents, labeled peptides were then used. Peptides are easier to synthesize, less likely to be immunogenic, and have rapid blood clearance, which results in adequate target-to-background ratios in a short period of time. This review discusses state-of-the-art cancer imaging by means of labeled peptides, the radionuclide, optical and nanoplatform-based imaging techniques which can provide functional information of the disease and track biochemical processes in vivo. The advantages and disadvantages of each technique are discussed. Lastly, the emphasis of this paper is on the new multimodal probes which can overcome individual limitations and exploit the individual strengths of the latest molecular imaging techniques

Experimental setup for light-to-heat NIR conversion measurements of gold nanoparticle solutions

In recent years, there is a constantly increasing interest in the application of nanoparticles for cancer diagnosis and cancer therapy. In this respect, the most promising nano-objects at present are the gold nanoparticles. A very convenient and powerful property of these objects is their ability to increase their temperature under electro-magnetic irradiation with certain wavelength. In our research we have directed our efforts toward particular nano-objects specifically sensitive to electromagnetic radiation in the near-infrared region (NIR). In order to study the photothermic properties of the solutions of gold nanoparticles in the NIR we constructed a specific electronic setup consisting of a laser system with interchangeable laser diodes with different wavelength NIR light, a thermally-insulated cuvette-holder compartment with temperature measuring probes and a NIR spectrometer to control the stimulated fluorescence emission of the nanoparticle solutions. The temperature measurement compartment with the thermal-insulated cuvette holder was designed to maintain the solutions’ temperature at a fixed value right before the moment of laser irradiation. To maintain the measurement setup at a fixed temperature before the irradiation we used a thermal stabilized system based on two Peltier cells with electronic temperature control. The temperatures of the ambient air and the temperature of the cuvette walls were continuously measured in order to make corrections about the temperature dissipation during the irradiation