Receptor-based radiopharmaceuticals are of great current interest in molecular imaging and radiotherapy of cancers, and provide a unique tool for target-specific delivery of radionuclides to the ...diseased tissues. In general, a target-specific radiopharmaceutical can be divided into four parts: targeting biomolecule (BM), pharmacokinetic modifying (PKM) linker, bifunctional coupling or chelating agent (BFC), and radionuclide. The targeting biomolecule serves as a “carrier” for specific delivery of the radionuclide. PKM linkers are used to modify radiotracer excretion kinetics. BFC is needed for radiolabeling of biomolecules with a metallic radionuclide. Different radiometals have significant difference in their coordination chemistry, and require BFCs with different donor atoms and chelator frameworks. Since the radiometal chelate can have a significant impact on physical and biological properties of the target-specific radiopharmaceutical, its excretion kinetics can be altered by modifying the coordination environment with various chelators or coligand, if needed. This review will focus on the design of BFCs and their coordination chemistry with technetium, copper, gallium, indium, yttrium and lanthanide radiometals.
We compare the yields of {sup 44}Ti and {sup 56}Ni produced from post-processing the thermodynamic trajectories from three different core-collapse models-a Cassiopeia A progenitor, a double shock ...hypernova progenitor, and a rotating two-dimensional explosion-with the yields from exponential and power-law trajectories. The peak temperatures and densities achieved in these core-collapse models span several of the distinct nucleosynthesis regions we identify, resulting in different trends in the {sup 44}Ti and {sup 56}Ni yields for different mass elements. The {sup 44}Ti and {sup 56}Ni mass fraction profiles from the exponential and power-law profiles generally explain the tendencies of the post-processed yields, depending on which regions are traversed by the model. We find that integrated yields of {sup 44}Ti and {sup 56}Ni from the exponential and power-law trajectories are generally within a factor two or less of the post-process yields. We also analyze the influence of specific nuclear reactions on the {sup 44}Ti and {sup 56}Ni abundance evolution. Reactions that affect all yields globally are the 3{alpha}, p(e{sup -}, {nu}{sub e})n and n(e{sup +},{nu}-bar{sub e})p. The rest of the reactions are ranked according to their degree of impact on the synthesis of {sup 44}Ti. The primary ones include {sup 44}Ti({alpha}, p){sup 47}V, {sup 40}Ca({alpha}, {gamma}){sup 44}Ti, {sup 45}V(p, {gamma}){sup 46}Cr, {sup 40}Ca({alpha}, p){sup 43}Sc, {sup 17}F({alpha}, p){sup 20}Ne, {sup 21}Na({alpha}, p){sup 24}Mg, {sup 41}Sc(p, {gamma}){sup 42}Ti, {sup 43}Sc(p, {gamma}){sup 44}Ti, {sup 44}Ti(p, {gamma}){sup 45}V, and {sup 57}Ni(p, {gamma}){sup 58}Cu, along with numerous weak reactions. Our analysis suggests that not all {sup 44}Ti need to be produced in an {alpha}-rich freeze-out in core-collapse events, and that reaction rate equilibria in combination with timescale effects for the expansion profile may account for the paucity of {sup 44}Ti observed in supernova remnants.
G protein-coupled receptor agonists are being used as radiolabeled vectors for in vivo localization and therapy of tumors. Recently, somatostatin-based antagonists were shown to be superior to ...agonists. Here, we compare the new 111In/68Ga-labeled bombesin-based antagonist RM1 with the agonist 111In-AMBA for targeting the gastrin-releasing peptide receptor (GRPR).
IC50, Kd values, and antagonist potency were determined using PC-3 and HEK-GRPR cells. Biodistribution and imaging studies were done in nude mice transplanted with the PC-3 tumor. The antagonist potency was assessed by evaluating the effects on calcium release and on receptor internalization monitored by immunofluorescence microscopy.
The IC50 value of (nat)In-RM1 was 14 +/- 3.4 nmol/L. (nat/111)In-RM1 was found to bind to the GRPR with a Kd of 8.5 +/- 2.7 nmol/L compared with a Kd of 0.6 +/- 0.3 nmol/L of 111In-AMBA. A higher maximum number of binding site value was observed for 111In-RM1 (2.4 +/- 0.2 nmol/L) compared with 111In-AMBA (0.7 +/- 0.1 nmol/L). (nat)Lu-AMBA is a potent agonist in the immunofluorescence-based internalization assay, whereas (nat)In-RM1 is inactive alone but efficiently antagonizes the bombesin effect. These data are confirmed by the calcium release assay. The pharmacokinetics showed a superiority of the radioantagonist with regard to the high tumor uptake (13.4 +/- 0.8% IA/g versus 3.69 +/- 0.75% IA/g at 4 hours after injection. as well as to all tumor-to-normal tissue ratios.
Despite their relatively low GRPR affinity, the antagonists 111In/68Ga-RM1 showed superior targeting properties compared with 111In-AMBA. As found for somatostatin receptor-targeting radiopeptides, GRP-based radioantagonists seem to be superior to radioagonists for in vivo imaging and potentially also for targeted radiotherapy of GRPR-positive tumors.
Induction of apoptosis is often necessary for successful cancer therapy, and the non-invasive monitoring of apoptosis post-therapy could assist in clinical decision making. Isatins are a class of ...compounds that target activated caspase-3 during apoptosis. Here we report the synthesis of the 5-iodo-1,2,3-triazole (FITI) analog of the PET tracer
FICMT11 as a candidate tracer for imaging of apoptosis with SPECT, as well as PET. Labelling with radioiodine (
I) was achieved in 55 ± 12% radiochemical yield through a chelator-accelerated one-pot cycloaddition reaction mediated by copper(I) catalysis. The caspase-3 binding affinity and selectivity of FITI compares favourably to that of
FICMT11 (K
= 6.1 ± 0.9 nM and 12.4 ± 4.7 nM, respectively). In biodistribution studies, etoposide-induced cell death in a SW1222 xenograft model resulted in a 2-fold increase in tumour uptake of the tracer. However, the tumour uptake was too low to allow in vivo imaging of apoptosis with SPECT.
Nuclear Data Sheets for A = 133 Khazov, Yu; Rodionov, A.; Kondev, F.G.
Nuclear data sheets,
04/2011, Letnik:
112, Številka:
4
Journal Article
Recenzirano
Evaluated nuclear structure and decay data for all nuclei within the A=133 mass chain are presented. The experimental data are evaluated and best values for level and gamma-ray energies, quantum ...numbers, lifetimes, gamma-ray intensities, and other nuclear properties are recommended. Inconsistencies and discrepancies that exist in the literature are noted. This work supersedes the earlier evaluation by S. Raab (1995Ra12), published in
Nuclear Data Sheets
75, 491 (1995).
The high affinity and specificity of peptides towards biological targets, in addition to their favorable pharmacological properties, has encouraged the development of many peptide-based ...pharmaceuticals, including peptide-based positron emission tomography (PET) radiopharmaceuticals. However, the poor in vivo stability of unmodified peptides against proteolysis is a major challenge that must be overcome, as it can result in an impractically short in vivo biological half-life and a subsequently poor bioavailability when used in imaging and therapeutic applications. Consequently, many biologically and pharmacologically interesting peptide-based drugs may never see application. A potential way to overcome this is using peptide analogues designed to mimic the pharmacophore of a native peptide while also containing unnatural modifications that act to maintain or improve the pharmacological properties. This review explores strategies that have been developed to increase the metabolic stability of peptide-based pharmaceuticals. It includes modifications of the
- and/or
-termini, introduction of d- or other unnatural amino acids, backbone modification, PEGylation and alkyl chain incorporation, cyclization and peptide bond substitution, and where those strategies have been, or could be, applied to PET peptide-based radiopharmaceuticals.
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