The impact of HF-rTMS treatment on serotonin(2A) receptors in unipolar melancholic depression.

Background: Currently, the underlying neurobiological mechanism as to how repetitive transcranial magnetic stimulation (rTMS) can alter depressive states remains unclear. Animal data suggest that its influence could occur at the neurotransmitter level, such as modulation of the serotonin system.

Methods: Twenty-one antidepressant-free medication-resistant unipolar depressed patients, and 21 age- and gender-matched healthy subjects were studied.

Preliminary in vivo evaluation of [131I]-2-iodo-D-phenylalanine as a potential radionuclide therapeutic agent in R1M-fluc rhabdomyosarcoma tumor-bearing NuNu mice using bioluminescent imaging.

Background: Carrier-added [(123)I]-2-iodo-D-phenylalanine (CA [(123)I]-2-I-D-Phe) was previously found to have a preferential retention in tumors with a high tumor background contrast in animal models. A previous human dosimetry study demonstrated a favorable biodistribution and radiation burden in human subjects.

Aim: The aim of this study was to investigate the potential of CA [(131)I]-2-I-D-Phe as an agent for radionuclide therapy.

A critical quantum chemical and experimental study of the potentiality of direct labeling of the CN group with [(99m)Tc(CO)(3)](+) or [(186/188)Re(CO)(3)](+) in CN containing biomolecules.

Introduction: It was determined recently that [(99m)Tc(OH(2))(2)(X(-))(CO(3))(3)] could strongly bind to the CN group, allowing direct labeling of CN in vitamin B(12) despite the presence of a benzimidazole group. The aim of this paper was to perform a critical study of this potentiality, coupling quantum chemical calculations to experimental evidence.

Methods: Computational methods: Within the density functional theory calculations, the 6-31+G basis set (C, H, O, N atoms) and the LANL2DZ basis set (Tc,Re) were used.

Method for stabilizing non carrier added 2-[(18)F]fluoromethyl-l-phenylalanine, a new tumour tracer, during radiosynthesis and radiopharmaceutical formulation.

Introduction: Non carrier added (NCA) 2-[(18)F]fluoromethyl-l-phenylalanine is currently used in a Phase I study. Improvement of the stability of the fluorobenzyl analogue, very sensitive to defluorination and hydrolysis, during the synthetic route and in the radiopharmaceutical formulation was devised.

Methods: The protected brominated precursor was synthesised in three steps.

The use of [123I]-2-iodo-L-phenylalanine as an early radiotherapy evaluation tool: in vitro R1M rabdomyosarcoma cell and in vivo mouse experiments.

Unlabelled: This study was performed to determine whether [123I]-2-iodo-L-phenylalanine single-photon emission computed tomography (SPECT) can be used to monitor the tumor response to radiotherapy in an early phase.

Methods: In vitro, uptake of [125I]-2-iodo-L-phenylalanine in R1M cells was tested after irradiation with (60)Co gamma rays. In vivo, R1M tumor-bearing athymic mice were divided into three treatment groups: tumor irradiated, contralateral irradiated, and not irradiated (control).

Intra-individual comparison of the human biodistribution and dosimetry of the D and L isomers of 2-[123I]iodo-phenylalanine.

Purpose: Several authors have shown in animal studies that D-enantiomeric amino acid analogues can have better tumour imaging properties compared to their L-analogues. In our group, the D and L isomers of 2-[I]iodo-phenylalanine were identified as tumour-specific tracers in rat and mouse tumour models, with an advantage for the D-isomer. Here we compare, intra-individually, the normal biodistribution and dosimetry of both tracers in healthy human subjects.

D- and L-[123I]-2-I-phenylalanine show a long tumour retention compared with D- and L-[123I]-2-I-tyrosine in R1M rhabdomyosarcoma tumour-bearing Wag/Rij rats.

The aim of this study was the comparison of the tumour uptake and the long-term retention of [(123)I]-2-I-L-phenylalanine and [(123)I]-2-I-D-phenylalanine with those of [(123)I]-2-I-L-tyrosine and [(123)I]-2-I-D-tyrosine in R1M rhabdomyosarcoma tumour-bearing rats. The biodistribution of the radioactivity as a function of time in R1M tumour-bearing rats was measured by planar gamma camera imaging (dynamic and static). If dissection was applied, the activity in the tumours and tissues of interest was measured by gamma counting.

123I-2-iodo-tyrosine, a new tumour imaging agent: human biodistribution, dosimetry and initial clinical evaluation in glioma patients.

Purpose: 123I-2-iodo-tyrosine (123I-2IT) has been identified as a promising new amino acid tracer in animals. Uptake is mediated by LAT1 transport, which is increased in tumour cells. In this study we present the human biodistribution and first clinical results in glioma patients.

Amino acids labeled with [99mTc(CO)3]+ and recognized by the L-type amino acid transporter LAT1.

We have synthesized amino acids conjugated at the alpha-carbon through an alkyl spacer to a small tripod ligand. The tripod coordinates to the fac-[M(CO)3]+ moiety (M = Re, 99mTc). Depending on the lengths of the spacers, these metal complexes with pendent alpha-amino acids are recognized and transported by the l-type amino acid transporter LAT1.

Comparison of the uptake of [123/125I]-2-iodo-D-tyrosine and [123/125I]-2-iodo-L-tyrosine in R1M rhabdomyosarcoma cells in vitro and in R1M tumor-bearing Wag/Rij rats in vivo.

Introduction: Recently, promising results concerning uptake in vivo in tumors of D-amino acids have been published. Therefore, we decided to evaluate the tumor uptake of the D-analogue of [(123)I]-2-iodo-L-tyrosine, a tracer recently introduced by our group into clinical trials. The uptake of 2-amino-3-(4-hydroxy-2-[(123/125)I]iodophenyl)-D-propanoic acid (2-iodo-D-tyrosine) was studied in vitro in LAT1-expressing R1M rat rhabdomyosarcoma cells and in vivo in R1M tumor-bearing Wag/Rij rats.

Optimization by experimental design of precursor synthesis and radiolabeling of 2-iodo-L-phenylalanine, a novel amino acid for tumor imaging.

Various radiolabeled amino acids show promising results in tumor detection, as applied in the management of cancer patients. We synthesized the precursor 2-iodo-L-phenylalanine for easier kit labeling of [123/125I]- 2-iodo-L-phenylalanine, using the Cu1+ -assisted nucleophilic halogen exchange. Precursor synthesis was optimized by experimental design: Eight parameters were initially screened by a quarter fractional design.

123/125I-labelled 2-iodo-L: -phenylalanine and 2-iodo-D: -phenylalanine: comparative uptake in various tumour types and biodistribution in mice.

Purpose: In vitro in the R1M cell model and in vivo in the R1M tumour-bearing athymic model, both [(123)I]-2-iodo-L: -phenylalanine and [(123)I]-2-iodo-D: -phenylalanine have shown promising results as tumour diagnostic agents for SPECT. In order to compare these two amino acid analogues and to examine whether the observed characteristics could be generalised, both isomers were evaluated in various tumour models.

Methods: Transport type characterisation in vitro in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M cells with [(123)I]-2-iodo-L: -phenylalanine was performed using the method described by Shotwell et al.

Influence of sedation and data acquisition method on tracer uptake in animal models: [123I]-2-iodo-L-phenylalanine in pentobarbital-sedated tumor-bearing athymic mice.

Objectives: To minimize movement artifacts during tracer imaging studies, the animals are generally sedated. Although many reports describe the effect of barbiturates on brain function, less is published about the general impact on the extracerebral metabolism and tracer biodistribution. This report describes the influence of pentobarbital on tumor uptake of [(123)I]-2-iodo-L-phenylalanine ([(123)I]-2I-L-PA) using dissection and nuclear imaging.

Comparative biodistribution study of the new tumor tracer [123I]-2-iodo-L-phenylalanine with [123I]-2-iodo-L-tyrosine.

Introduction: Both A- and l-type amino acid transport are increased in tumor cells relative to normal tissue; these transport systems have been the major focus of the development of amino acid tumor tracers to overcome the limitations of [(18)F]-fluorodeoxyglucose ((18)F-FDG). The newly developed tracer 2-amino-3-(2-[(123)I]iodophenyl)propanoic acid ([(123)I]-2-iodo-l-phenylalanine) showed high and specific tumor uptake, slow renal elimination and low brain uptake. We compared [(123)I]-2-iodo-L-phenylalanine with 2-amino-3-(4-hydroxy-2-[(123)I]iodophenyl)propanoic acid ([(123)I]-2-iodo-L-tyrosine), an L-tyrosine analogue that has recently entered clinical trials.

In vivo evaluation and dosimetry of 123I-2-iodo-D-phenylalanine, a new potential tumor-specific tracer for SPECT, in an R1M rhabdomyosarcoma athymic mouse model.

Unlabelled: Earlier reports described the preferential uptake of d-amino acids in tumor-bearing mice. Moreover, it was shown that in tumor cells in vitro the L-amino acid transporter system seemed to lack stereospecificity. Because of the successful results with 123/125I-2-iodo-L-phenylalanine, 123/125I-2-iodo-D-phenylalanine was developed, and its tumor-detecting characteristics were evaluated in vivo.

In vivo characterization of 123/125I-2-iodo-L-phenylalanine in an R1M rhabdomyosarcoma athymic mouse model as a potential tumor tracer for SPECT.

Unlabelled: The application of 123I-3-iodo-alpha-methyltyrosine is limited to diagnosis of brain tumors due to its marked long-term uptake in kidneys. In vitro evaluation of 125I-2-iodo-L-phenylalanine showed high uptake in R1M cells by L-type amino acid transport system 1 (LAT1). This study evaluates 123I-2-iodo-L-phenylalanine as a new specific tumor tracer for SPECT.

SPECT and PET amino acid tracer influx via system L (h4F2hc-hLAT1) and its transstimulation.

Unlabelled: System L amino acid transport is increased in various types of cancer. The tracer 123I-2-iodotyrosine (2IT), which is accumulated via system L, could thus serve to allow visualization of cancer in vivo. Here, we studied the transport of 125I-2IT by h4F2hc-hLAT1, the major transporter subserving system L in growing cells, using the Xenopus laevis oocyte expression system.

Estimates of regional cerebral blood flow and 5-HT2A receptor density in impulsive, aggressive dogs with 99mTc-ECD and 123I-5-I-R91150.

Impulsive aggression in dogs has an important impact on human public health. Better insight into the pathophysiology of this phenomenon could lead to more adequate diagnosis and treatment. Indirect in vivo research on peripheral body fluids and post-mortem studies in impulsive animals and humans indicate a deficient serotonergic system in general and disturbances in the serotonin-2A (5-HT2A) receptor in particular.

Comparative biodistribution of iodinated amino acids in rats: selection of the optimal analog for oncologic imaging outside the brain.

Unlabelled: 3-(123)I-Iodo-alpha-methyltyrosine ((123)I-3-IMT) is used for the detection of residual and recurrent brain tumors. The application of (123)I-3-IMT for the study of extracerebral malignancies is limited by its marked and rapid renal uptake. In this study, we compared the tumor uptake, biodistribution, and specificity of 5 structurally related iodinated amino acids with those of (123)I-3-IMT.

Decreased 5-HT2a receptor binding in patients with anorexia nervosa.

Unlabelled: Indirect estimations of brain neurotransmitters in patients with anorexia nervosa (AN) and low weight have demonstrated a reduction in brain serotonin (5-HT) turnover in general and led to hypotheses about dysfunction in the 5-HT(2a) receptor system. It was our aim to investigate the central 5-HT(2a) receptor binding index using SPECT brain imaging.

Methods: The 5-HT(2a) receptors of low-weight patients with AN were studied by means of the highly specific radioiodinated 5-HT(2a) receptor antagonist 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide or (123)I-5-I-R91150.

Effects of aging on brain perfusion and serotonin-2A receptor binding in the normal canine brain measured with single photon emission tomography.

Normal aging is associated with a decrease in number and size of neurons, loss of synapses and neuronal branching and with a reduced functioning neurotransmitter systems, such as the serotonergic system. These structural and functional alterations have important impact on the behavioural, cognitive and affective status of the individual. With the introduction of functional brain imaging in veterinary medicine, the canine brain can be examined in vivo, evaluating changes in perfusion, metabolism and neurotransmitter systems.

Increased tumor uptake of 3-(123)I-Iodo-L-alpha-methyltyrosine after preloading with amino acids: an in vivo animal imaging study.

Unlabelled: 3-(123)I-Iodo-L-alpha-methyltyrosine (3-IMT) is an amino acid analog used for tumor imaging. Specific accumulation is mediated mainly by the system L amino acid transport system. System L activity is known to increase when cells are loaded with amino acids.