23 research outputs found
Production of therapeutic quantities of 64Cu and 119Sb for radionuclide therapy using a small PET cyclotron
Decay induced de-chelation of positron-emitting electron-capture daughters and its use in preclinical PET
Remote Loading of <sup>64</sup>Cu<sup>2+</sup> into Liposomes without the Use of Ion Transport Enhancers
Due to low ion permeability of lipid bilayers, it has
been and still is common practice to use transporter molecules such
as ionophores or lipophilic chelators to increase transmembrane diffusion
rates and loading efficiencies of radionuclides into liposomes. Here,
we report a novel and very simple method for loading the positron
emitter <sup>64</sup>Cu<sup>2+</sup> into liposomes, which is important
for <i>in vivo</i> positron emission tomography (PET) imaging.
By this approach, copper is added to liposomes entrapping a chelator,
which causes spontaneous diffusion of copper across the lipid bilayer
where it is trapped. Using this method, we achieve highly efficient <sup>64</sup>Cu<sup>2+</sup> loading (>95%), high radionuclide retention
(>95%), and favorable loading kinetics, excluding the use of transporter
molecule additives. Therefore, clinically relevant activities of 200–400
MBq/patient can be loaded fast (60–75 min) and efficiently
into preformed stealth liposomes avoiding subsequent purification
steps. We investigate the molecular coordination of entrapped copper
using X-ray absorption spectroscopy and demonstrate high adaptability
of the loading method to pegylated, nonpegylated, gel- or fluid-like,
cholesterol rich or cholesterol depleted, cationic, anionic, and zwitterionic
lipid compositions. We demonstrate high <i>in vivo</i> stability
of <sup>64</sup>Cu-liposomes in a large canine model observing a blood
circulation half-life of 24 h and show a tumor accumulation of 6%
ID/g in FaDu xenograft mice using PET imaging. With this work, it
is demonstrated that copper ions are capable of crossing a lipid membrane
unassisted. This method is highly valuable for characterizing the <i>in vivo</i> performance of liposome-based nanomedicine with
great potential in diagnostic imaging applications
PET/CT Based In Vivo Evaluation of 64Cu Labelled Nanodiscs in Tumor Bearing Mice
64Cu radiolabelled nanodiscs based on the 11 α-helix MSP1E3D1 protein and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipids were, for the first time, followed in vivo by positron emission tomography for evaluating the biodistribution of nanodiscs. A cancer tumor bearing mouse model was used for the investigations, and it was found that the approximately 13 nm nanodiscs, due to their size, permeate deeply into cancer tissue. This makes them promising candidates for both drug delivery purposes and as advanced imaging agents. For the radiolabelling, a simple approach for 64Cu radiolabelling of proteins via a chelating agent, DOTA, was developed. The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid-protein particle while fully conserving the particle structure including the amphipathic protein fold
Head-to-head comparison of <sup>64</sup>Cu-DOTATATE and<sup> 68</sup>Ga -DOTATOC PET/CT: a prospective study of 59 patients with neuroendocrine tumors
Liposome accumulation in irradiated tumors display important tumor and dose dependent differences
Novel Preparation Methods of <sup>52</sup>Mn for ImmunoPET Imaging
52Mn (t1/2 =5.59 d, ß+ = 29.6%, Eßave = 0.24 MeV) shows promise in positron emission tomography (PET) and in dual-modality manganese-enhanced magnetic resonance imaging (MEMRI) applications including neural tractography, stem cell tracking, and biological toxicity studies. The extension to bioconjugate application requires high specific activity 52Mn in a state suitable for macromolecule labeling. To that end a 52Mn production, purification, and labeling system is presented, and its applicability in preclinical, macromolecule PET is shown using the conjugate 52Mn-DOTA-TRC105. 52Mn is produced by 60 µA, 16 MeV proton irradiation of natural chromium metal pressed into a silver disc support. Radiochemical separation proceeds by strong anion exchange chromatography of the dissolved Cr target, employing a semi-organic mobile phase, 97:3 (v:v) ethanol: HCl (11M, aqueous). The method is 62 ± 14% efficient (n=7) in 52Mn recovery, leading to a separation factor from Cr of (1.6 ± 1.0) x106 (n = 4), and an average effective specific activity of 0.8 GBq/µmol (n = 4) in titration against DOTA. 52Mn-DOTA-TRC105 conjugation and labeling demonstrate the potential for chelation applications. In vivo images acquired using PET/CT in mice bearing 4T1 xenograft tumors are presented. Peak tumor uptake is 18.7 ± 2.7 %ID/g at 24 hours post injection and ex vivo 52Mn biodistribution validates the in vivo PET data. Free 52Mn2+(as chloride or acetate) is used as a control in additional mice to evaluate the non-targeted biodistribution in the tumor model