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Patricia Antunes

Other affiliations: Instituto Superior Técnico
Bio: Patricia Antunes is an academic researcher from University Hospital of Basel. The author has contributed to research in topics: DOTA & Cancer. The author has an hindex of 6, co-authored 7 publications receiving 534 citations. Previous affiliations of Patricia Antunes include Instituto Superior Técnico.

Papers
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Journal ArticleDOI
TL;DR: This study demonstrates that 67/68Ga-DOTA-octapeptides show distinctly better preclinical, pharmacological performances than the 111In-labelled peptides, especially on sst2-expressing cells and the corresponding animal models, and may be excellent candidates for further development for clinical studies.
Abstract: Purpose Gallium-68 is a metallic positron emitter with a half-life of 68 min that is ideal for the in vivo use of small molecules, such as [68Ga-DOTA,Tyr3]octreotide, in the diagnostic imaging of somatostatin receptor-positive tumours. In preclinical studies it has shown a striking superiority over its 111In-labelled congener. The purpose of this study was to evaluate whether third-generation somatostatin-based, radiogallium-labelled peptides show the same superiority.

361 citations

Journal ArticleDOI
TL;DR: A significant 1.2-fold improvement in the specific internalization rate in AR4-2J rat pancreatic tumor cells (sst2 receptor expression) at 4 h was achieved with the introduction of Asp as a spacer in the parent compound, and the new conjugates preserved the good affinity for hsst5, except for [InIII-DOTA]-Asn(GlcNAc)-NOC, which showed decreased affinity.

77 citations

Journal ArticleDOI
TL;DR: Biodistribution studies in mice demonstrated that (153)Sm/(166)Ho-trita complexes have a fast tissue clearance with more than 95% of the injected activity excreted after 2 h, value that is comparable to the corresponding dota complexes, in contrast, the ( 153)Sm-teta complex has a significantly lower total excretion.

61 citations

Journal ArticleDOI
21 Jun 2002-Langmuir
TL;DR: In this paper, two cationic porphyrins, the amphiphilic meso-tetra(4-N-stearylpyridyl)porphine (PO1) and the hydrophilic meson-to-methylpyridine (TMPyP or PO2), were incorporated in ionic diluent matrixes containing sodiumhexadecyl sulfate (SHS) and dioctadecyldimethylammonium bromide (DODAB) at the air-water interface and in
Abstract: Two cationic porphyrins, the amphiphilic meso-tetra(4-N-stearylpyridyl)porphine (PO1) and the hydrophilic meso-tetra(4-N-methylpyridyl)porphine (TMPyP or PO2), were incorporated in ionic diluent matrixes containing sodiumhexadecyl sulfate (SHS) and dioctadecyldimethylammonium bromide (DODAB) at the air-water interface and in Langmuir-Blodgett films. All systems containing PO1 show a preferential interaction of SHS with DODAB, instead of SHS with PO1. The cationic system PO1/SHS/DODAB at a 1:4:4 molar ratio behaves as the separate PO1 plus SHS + DODAB monolayers and forms H-type porphyrin aggregates at high π. The neutral system PO1/SHS/DODAB at a 1:8:4 molar ratio separates into PO1 + 4SHS plus SHS + DODAB monolayers, forming a PO1 + 4SHS bilayer at high π in which the porphyrin macrocycles can adopt "planar" and "nonplanar" conformations. The quenching efficiency of the PO1 fluorescence was found to be generally higher in the cationic, rather than neutral, monolayers and also to increase with the porphyrin surface concentration and number of deposited layers. Systems containing PO2 are generally not very stable at the air-water interface. The system PO2/4SHS forms H-type PO2 aggregates (or H-dimers) at low π and dissolves in water at high π. The system PO2/4SHS/4DODAB separates into the soluble PO2 plus the neutral SHS + DODAB monolayer. Only the neutral system PO2/8SHS/4DODAB is quite stable at the air-water interface because offavorable (cooperative) electrostatic and hydrophobic interactions.

27 citations

Journal ArticleDOI
TL;DR: Two novel benzodioxotetraaza macrocycles, synthesized by a [1 + 1] crablike cyclization, showed that the CuL1 complex has a much lower thermodynamic stability than theCuL2, and the H2L2 displays an excellent affinity for copper(II), due to the good fit of copper( II) into its cavity.
Abstract: Two novel benzodioxotetraaza macrocycles [2,9-dioxo-1,4,7,10-tetraazabicyclo[10.4.0]1,11-hexadeca-1(11),13,15-triene (H(2)L1) and 2,10-dioxo-1,4,8,11-tetraazabicyclo[11.4.0]1,12-heptadeca-1(12),14,16-triene (H(2)L2)] were synthesized by a [1 + 1] crablike cyclization. The protonation constants of both ligands were determined by H-1 NMR titration and by potentiometry at 25.0 degrees C in 0.10 M ionic strength in KNO3. The latter method was also used to ascertain the stability constants of their copper(II) complexes. These studies showed that the CuL1 complex has a much lower thermodynamic stability than the CuL2, and the H(2)L2 displays an excellent affinity for copper(II), due to the good fit of copper(II) into its cavity. The copper complexes of the novel ligands were characterized by electronic spectroscopy in solution and by crystal X-ray diffraction. These studies indicated that the copper center in the CuL1 complex adopts a square-pyramidal geometry with the four nitrogen atoms of the macrocycle forming the equatorial plane and a water molecule at axial position, and the copper in the CuL2 complex is square-planar. Several labeling conditions were tested, and only H(2)L2 could be labeled with Cu-67 efficiently (> 98%) in mild conditions (39 degrees C, 15 min) to provide a slightly hydrophilic radioligand (log D = -0.19 +/- 0.03 at pH 7.4). The in vitro stability was studied in the presence of different buffers or with an excess of diethylenetriamine-pentaethanoic acid. Very high stability was shown under these conditions for over 5 days. The incubation of the radiocopper complex in human serum showed 6% protein binding.

21 citations


Cited by
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Journal ArticleDOI
TL;DR: Targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications are summarized.
Abstract: Nanomaterials offer new opportunities for cancer diagnosis and treatment. Multifunctional nanoparticles harboring various functions including targeting, imaging, therapy, and etc have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. Of various nanoparticles, magnetic iron oxide nanoparticles with superparamagnetic property have shown potential as multifunctional nanoparticles for clinical translation because they have been used asmagnetic resonance imaging (MRI) constrast agents in clinic and their features could be easily tailored by including targeting moieties, fluorescence dyes, or therapeutic agents. This review summarizes targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications.

739 citations

Journal ArticleDOI
TL;DR: The ligand types and structures of their complexes on one side and a set of the physico-chemical parameters governing properties of the CAs on the other side are discussed and the solid-state structures of lanthanide(III) complexes of open-chain and macrocyclic ligands and their structural features are compared.
Abstract: Magnetic resonance imaging is a commonly used diagnostic method in medicinal practice as well as in biological and preclinical research. Contrast agents (CAs), which are often applied are mostly based on Gd(III) complexes. In this paper, the ligand types and structures of their complexes on one side and a set of the physico-chemical parameters governing properties of the CAs on the other side are discussed. The solid-state structures of lanthanide(III) complexes of open-chain and macrocyclic ligands and their structural features are compared. Examples of tuning of ligand structures to alter the relaxometric properties of gadolinium(III) complexes as a number of coordinated water molecules, their residence time (exchange rate) or reorientation time of the complexes are given. Influence of the structural changes of the ligands on thermodynamic stability and kinetic inertness/lability of their lanthanide(III) complexes is discussed.

469 citations

Journal ArticleDOI
TL;DR: The tailor-made DOTA-conjugated PSMA inhibitor PSMA-617 presented here is sustainably refined and advanced with respect to its tumor-targeting and pharmacokinetic properties by systematic chemical modification of the linker region.
Abstract: Despite many advances in the past years, the treatment of metastatic prostate cancer still remains challenging. In recent years, prostate-specific membrane antigen (PSMA) inhibitors were intensively studied to develop low-molecular-weight ligands for imaging prostate cancer lesions by PET or SPECT. However, the endoradiotherapeutic use of these compounds requires optimization with regard to the radionuclide-chelating agent and the linker moiety between chelator and pharmacophore, which influence the overall pharmacokinetic properties of the resulting radioligand. In an effort to realize both detection and optimal treatment of prostate cancer, a tailor-made novel naphthyl-containing DOTA-conjugated PSMA inhibitor has been developed. Methods: The peptidomimetic structure was synthesized by solid-phase peptide chemistry and characterized using reversed-phase high-performance liquid chromatography and matrix-assisted laser desorption/ionization mass spectrometry. Subsequent 67/68Ga and 177Lu labeling resulted in radiochemical yields of greater than 97% or greater than 99%, respectively. Competitive binding and internalization experiments were performed using the PSMA-positive LNCaP cell line. The in vivo biodistribution and dynamic small-animal PET imaging studies were investigated in BALB/c nu/nu mice bearing LNCaP xenografts. Results: The chemically modified PSMA inhibitor PSMA-617 demonstrated high radiolytic stability for at least 72 h. A high inhibition potency (equilibrium dissociation constant [Ki] = 2.34 ± 2.94 nM on LNCaP; Ki = 0.37 ± 0.21 nM enzymatically determined) and highly efficient internalization into LNCaP cells were demonstrated. The small-animal PET measurements showed high tumor-to-background contrasts as early as 1 h after injection. Organ distribution revealed specific uptake in LNCaP tumors and in the kidneys 1 h after injection. With regard to therapeutic use, the compound exhibited a rapid clearance from the kidneys from 113.3 ± 24.4 at 1 h to 2.13 ± 1.36 percentage injected dose per gram at 24 h. The favorable pharmacokinetics of the molecule led to tumor-to-background ratios of 1,058 (tumor to blood) and 529 (tumor to muscle), respectively, 24 h after injection. Conclusion: The tailor-made DOTA-conjugated PSMA inhibitor PSMA-617 presented here is sustainably refined and advanced with respect to its tumor-targeting and pharmacokinetic properties by systematic chemical modification of the linker region. Therefore, this radiotracer is suitable for a first-in-human theranostic application and may help to improve the clinical management of prostate cancer in the future.

425 citations

Journal ArticleDOI
TL;DR: These guidelines are to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin (SST) receptor PET/CT imaging using 68Ga-DOTA-conjugated peptides, analogues of octreotide, that bind to SST receptors.
Abstract: The aim of these guidelines is to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin (SST) receptor PET/CT imaging using 68Ga-DOTA-conjugated peptides, analogues of octreotide, that bind to SST receptors. This imaging modality should not be regarded as the only approach to visualizing tumours expressing SST receptors or as excluding other imaging modalities useful for obtaining comparable results. The corresponding guidelines of 111In-pentetreotide scintigraphy imaging have been considered and partially integrated with this text. The same has been done with the relevant and recent literature in this field and the final result has been discussed by distinguished experts.

376 citations

Journal ArticleDOI
TL;DR: In this paper, a variety of mono-and bifunctional chelators have been developed which allow the formation of stable (68)Ga(3+)complexes and convenient coupling to biomolecules.
Abstract: PET (positron emission tomography) is a powerful diagnostic and imaging technique which requires short-lived positron emitting isotopes. The most commonly used are accelerator-produced (11)C and (18)F. An alternative is the use of metallic positron emitters. Among them (68)Ga deserves special attention because of its availability from long-lived (68)Ge/(68)Ga generator systems which render (68)Ga radiopharmacy independent of an onsite cyclotron. The coordination chemistry of Ga(3+) is dominated by its hard acid character. A variety of mono- and bifunctional chelators have been developed which allow the formation of stable (68)Ga(3+)complexes and convenient coupling to biomolecules. (68)Ga coupling to small biomolecules is potentially an alternative to (18)F- and (11)C-based radiopharmacy. In particular, peptides targeting G-protein coupled receptors overexpressed on human tumour cells have shown preclinically and clinically high and specific tumour uptake. Kit-formulated precursors along with the generator may be provided, similar to the (99)Mo/(99m)Tc-based radiopharmacy, still the mainstay of nuclear medicine.

311 citations