Radiation effective dose assessment of [51Mn]- and [52Mn]-chloride

In order to establish the potential of [51/52Mn]Cl2 as safe PET brain tracers, the radiation effective dose (ED) of [51Mn]- and [52Mn]-chloride has been assessed by using biokinetic models in anthropomorphic phantoms. Results showed that [52Mn]-chloride releases one hundred thirty times more radiation dose (ED = 1.35 mSv/MBq) than [51Mn]-chloride (ED = 1.02E-02 mSv/MBq). Although the maximum positron energy of 52Mn allows a PET image resolution similar to that of 18F, activities below 15 MBq should be administered

Bioconjugated technetium carbonyls by transmetalation reaction with zinc derivatives

Altres ajuts: Acord transformatiu CRUE-CSICThe transmetalation reaction between zinc dithiocarbamates functionalized with organic groups and the cation fac-[Tc(HO)(CO)] has been studied as a new strategy to bind biomolecules to this radionuclide for preparing radiopharmaceuticals with high molar activity. All complexes were obtained in high yields by heating at moderate temperatures and without subsequent purification. The chemical identity was ascertained by HPLC comparison with the homologous rhenium complexes. Stability studies in cysteine solution and serum have shown a good stability of the coordination set fac-[Tc(CO)(SS)(P)]. Preliminary biological studies of the radiocomplex functionalized with D-(+)-glucosamine with carcinoma cells have been performed

Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using direct 100Mo(p,2n) reaction

Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets at low proton energies (i.e. within 15\u201320 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states (9xTc) present in the pertechnetate saline Na99mTcO4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate (99mTc) injection 4801\u20133). Moreover, the impact of 9xTc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99mTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E \u3b3 \u2009\u2009>\u2009\u2009200\u2009keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction at a proton beam energy in the range 15.7\u201319.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99mTc

Una formulación liofilizada para la preparación de Lys27(99MTc-EDDA/HYNIC)-Exendin(9-39)/99MTc-EDDA/HYNIC-TYR3-Octreótido para de-tectar insulinomas benignos y malignos

Los insulinomas son tumores pequeños con síntomas severos de hiperinsulinemia que pueden resultar en daños cerebrales permanentes si no se tratan de ma-nera temprana. Son muy difíciles de detectar por métodos convencionales. El tratamiento de elección es la cirugía, por lo que es necesaria su adecuada localización preoperatoria. Aproximadamente 90% de los insulinomas son benignos y sobre-expresan receptores del péptido tipo 1 análogo del glucagón (GLP-1R) y bajos niveles de receptores de somatosta-tina (SSTR)

Hyaluronan is a natural and effective immunological adjuvant for protein-based vaccines

One of the main goals of vaccine research is the development of adjuvants that can enhance immune responses and are both safe and biocompatible. We explored the application of the natural polymer hyaluronan (HA) as a promising immunological adjuvant for protein-based vaccines. Chemical conjugation of HA to antigens strongly increased their immunogenicity, reduced booster requirements, and allowed antigen dose sparing. HA-based bioconjugates stimulated robust and long-lasting humoral responses without the addition of other immunostimulatory compounds and proved highly efficient when compared to other adjuvants. Due to its intrinsic biocompatibility, HA allowed the exploitation of different injection routes and did not induce inflammation at the inoculation site. This polymer promoted rapid translocation of the antigen to draining lymph nodes, thus facilitating encounters with antigen-presenting cells. Overall, HA can be regarded as an effective and biocompatible adjuvant to be exploited for the design of a wide variety of vaccines

Rhenium 188 labelling of peptide conjugates

Many human tumours express high levels, of somatostatin receptors. In order to make possible a radiotherapeutic treatment of this kind for tumour a series of somatostatin analogues that can tightly chelate beta emitting isotopes have been developed in recent years. The work carried out for this thesis has been aimed towards development of a new therapeutic radiopharmaceutical for treatment of somatostatin receptor positive tumours. The first chapters describe work with technetium-99m to establish the labelling and analytical conditions for a somatostatin analogue, [Tyr"3]-octreotide (TOC), as a precursor to undertaking labelling studies with the beta emitter rhenium-188. 6-Hydrazinopyridine-3-carboxylic acid (HYNIC) was conjugated to TOC and labelled with "9"9"m using different coligands. Then the stability, receptor binding and biodistribution of each complex were assessed. "9"9"mTc-HYNIC-TOC using EDDA as coligand showed the best characteristics, and was superior for tumour imaging in humans than the commercially available "1"1"1In-DTPA-octreotide. The conditions for labelling the HYNIC-TOC conjugate with "1"8"8Re were then optimised using tricine as a co-ligand. A labelling yield of #approx#80% was achieved. After purification however, the stability of the complex was low. The use of other coligand systems which had proved useful for "9"9"mTc labelling was explored, but yields were very poor. Other chelators such as diethylenetriamine pentaacetic acid (DTPA), dimercaptosuccinic acid (DMSA) and mercaptoacetyltriglycine (MAG_3) were studied as potential co-ligand agents to label the HYNIC-TOC conjugate with "1"8"8Re but, again low yields of the labelled peptide complexes were achieved. A novel "1"8"8Re-HYNIC complex was prepared in high yields using N-N-disubstituted dithiocarbamates as coligands. However to date, the specific activities achieved with this system are relatively low. The use of the ["9"9"mTc(CO)_3(H_2O)_3] complex to label the HYNIC-TOC conjugate was investigated. The labelling yield was 98%. Stability and biodistribution studies were performed showing that the complex was very stable, however an undesirable pattern of biodistribution, possibly caused by a high protein binding, was found. (author)Available from British Library Document Supply Centre- DSC:DXN057306 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Zirconium immune-complexes for PET molecular imaging: Current status and prospects

Diagnostic molecular images, obtained by positron emission tomography (PET), have successfully functioned as sensitive tools for detecting and monitoring the treatment of different diseases, mainly cancer. However, cancer proteomics has shown that the expression of specific molecular targets is dynamic, transforming nuclear molecular imaging techniques from purely diagnostic to procedures aimed at the prognosis of the disease for precise treatment selection. Of all commercially available pure PET radionuclides, zirconium-89 is the only one with a sufficient half-life (t1/2 = 3.27 d) to be useful for the labeling of antibodies, antibody fragments, cells, and nanoparticles. Therefore, the routine use of 89Zr–immunoPET is expected to help determine the prognosis and benefit of immunotherapies in cancer patients, such as anti-FAP, anti-CD44, anti-VEGF, anti-EGFR, anti-TGF-b, anti-PSMA, anti-STEAP1, anti-HER2/3, and/or anti-PD-L1. For this purpose, stable coordination of zirconium to bifunctional chelators is essential to form efficient radioimmunoconjugates with molecular targeting capabilities, which, combined with high PET resolution and sensitivity, could offer the most advanced tool for cancer prognosis, treatment definition and follow-up. In this manuscript, recent achievements concerning the coordination chemistry of zirconium (IV) to different chelators, the different molecular targets identified using immunoPET, the drug delivery systems based on 89Zr-antibody-drug conjugates/nanoparticles, and cell tracking with 89Zr, are reviewed and discussed

New bioconjugated technetium and rhenium folates synthesized by transmetallation reaction with zinc derivatives

The zinc dithiocarbamates functionalized with folic acid 2 and 3 were synthesized with a simple straightforward method, using an appropriated folic acid derivative and a functionalized zinc dithiocarbamate (1). Zinc complexes 2 and 3 show very low solubilities in water, making them useful for preparing Tc-99m radiopharmaceuticals with a potentially high molar activity. Thus, the transmetallation reaction in water medium between the zinc complexes 2 or 3 and the cation fac-[ Tc(H O) (CO) ], in the presence of the monodentate ligand TPPTS, leads to the formation of the 2 + 1 complexes fac-[ Tc(CO) (SS)(P)] bioconjugated to folic acid (2 and 3). In spite of the low solubility of 2 and 3 in water, the reaction yield is higher than 95%, and the excess zinc reagent is easily removed by centrifugation. The Tc-99m complexes were characterized by comparing their HPLC with those of the homologous rhenium complexes (2 and 3) previously synthesized and characterized by standard methods. Preliminary in vivo studies with 2 and 3 indicate low specific binding to folate receptors. In summary, Tc-99m folates 2 and 3 were prepared in high yields, using a one-pot transmetallation reaction with low soluble zinc dithiocarbamates (>1 ppm), at moderate temperature, without needing a subsequent purification step