5-HT2A receptors in the feline brain: 123I-5-I-R91150 kinetics and the influence of ketamine measured with micro-SPECT.

Unlabelled: Subanesthetic doses of ketamine can be used as a rapid-acting antidepressant in patients with treatment-resistant depression. Therefore, the brain kinetics of (123)I-5-I-R91150 (4-amino-N-[1-[3-(4-fluorophenyl)propyl]-4-methylpiperidin-4-yl]-5-iodo-2-methoxybenzamide) and the influence of ketamine on the postsynaptic serotonin-2A receptor (5-hydroxytryptamine-2A, or 5-HT2A) status were investigated in cats using micro-SPECT.

Methods: This study was conducted on 6 cats using the radioligand (123)I-5-I-R91150, a 5-HT2A receptor antagonist, as the imaging probe.

(99m)Tc-DMSA absolute and relative renal uptake in cats: procedure and normal values.

In this study we investigated the influence of technical factors (positioning, background (BG) correction and attenuation correction) on qualitative and quantitative (absolute (AU) and relative (RU) uptake) assessment of feline kidneys with (99m)technetium labelled dimercaptosuccinic acid ((99m)Tc-DMSA). Eleven healthy adult cats were included. Influence of BG and depth correction on quantitative assessment was evaluated.

Determination of optimal sampling times for a two blood sample clearance method using (51)Cr-EDTA in cats.

Estimation of the glomerular filtration rate (GFR) is a useful tool in the evaluation of kidney function in feline medicine. GFR can be determined by measuring the rate of tracer disappearance from the blood, and although these measurements are generally performed by multi-sampling techniques, simplified methods are more convenient in clinical practice. The optimal times for a simplified sampling strategy with two blood samples (2BS) for GFR measurement in cats using plasma (51)chromium ethylene diamine tetra-acetic acid ((51)Cr-EDTA) clearance were investigated.

Monoclonal antibody 14C5 targets integrin alphavbeta5.

This study identifies and characterizes the antigen recognized by monoclonal antibody (mAb) 14C5. We compared the expression of antigen 14C5 with the expression of eight integrin subunits (alpha1, alpha2, alpha3, alphav, beta1, beta2, beta3, and beta4) and three integrin heterodimers (alphavbeta3, alphavbeta5, and alpha5beta1) by flow cytometry. Antigen 14C5 showed a similar expression to alphavbeta5 in eight different epithelial cancer cell lines (A549, A2058, C32, Capan-2, Colo16, HT-1080, HT-29, and SKBR-3).

In vitro and in vivo evaluation of direct rhenium-188-labeled anti-CD52 monoclonal antibody alemtuzumab for radioimmunotherapy of B-cell chronic lymphocytic leukemia.

Alemtuzumab (Campath, Berlex) is a humanized IgG1 rat monoclonal antibody directed against the cell surface CD52 antigen, found on lymphocytes and monocytes. It is being developed for the treatment of chronic lymphocytic leukemia (CLL), autoimmune disease and for the prevention of transplant rejection. This study focused on synthesis, quality control, in vitro evaluation and biodistribution of (188)Re-labeled alemtuzumab for radioimmunotherapy of B-cell CLL.

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).

LC-UV/MS characterization and DOE optimization of the iodinated peptide obestatin.

The aim of this study was to investigate the direct iodination of the recently discovered peptide obestatin by LC-UV/ESI ion trap MS analysis. The influence of selected reaction parameters on obestatin iodination by chloramine-T, Iodo-Gen((R)) and lactoperoxidase was investigated by experimental design. Different responses, i.

Prognostic value of 99mTc-HYNIC annexin-V imaging in squamous cell carcinoma of the head and neck.

Purpose: The purpose of the study was to report on the prognostic value of (99m)Tc-hydrazinonicotinamide (HYNIC) Annexin-V single-photon emission computed tomography (SPECT) imaging in patients suffering from primary squamous cell carcinoma of the head and neck.

Methods: Twenty-nine patients diagnosed with a primary untreated head and neck squamous cell carcinoma were included in this study. In all patients, (99m)Tc-HYNIC Annexin-V scintigraphy SPECT was performed before treatment instigation.

Transdermal penetration behaviour of drugs: CART-clustering, QSPR and selection of model compounds.

A set of 116 structurally very diverse compounds, mainly drugs, was characterized by 1630 molecular descriptors. The biological property modelled in this study was the transdermal permeability coefficient logK(p). The main objective was to find a limited set of suitable model compounds for skin penetration studies.

Biodistribution and planar gamma camera imaging of (123)I- and (131)I-labeled F(ab')(2) and Fab fragments of monoclonal antibody 14C5 in nude mice bearing an A549 lung tumor.

Unlabelled: Detection of antigen 14C5, involved in substrate adhesion and highly expressed on the membrane of many carcinomas, including lung cancer, provides important diagnostic information that can influence patient management. The aim of this study was to evaluate the biodistribution and planar gamma camera imaging characteristics of radioiodinated F(ab')(2) and Fab fragments of monoclonal antibody (mAb) 14C5 in tumor-bearing mice.

Methods: F(ab')(2) and Fab 14C5 fragments were radioiodinated using the Iodo-Gen method.

Assessment of supra-additive effects of cytotoxic drugs and low dose rate irradiation in an in vitro model for hepatocellular carcinoma.

The use of 5-fluorouracil, topotecan, or gemcitabine was tested for enhancement of the effects of low dose rate (LDR) irradiation in an in vitro model for hepatocellular carcinoma. For comparison, all drugs were tested in combination with high dose rate (HDR) gamma-irradiation as well. Multicellular spheroids of HepG2 cells were exposed to HDR or LDR irradiation by means of external beam cobalt-60 or rhenium-188 (188Re), respectively, dissolved in the culture medium.

Annexin V detection of lipopolysaccharide-induced cardiac apoptosis.

Acute inflammatory response to lipopolysaccharide (LPS) exposure is typically associated with cardiac myocyte apoptosis, which is difficult to quantify because of heart tissue specificity. We report here that radioiodinated Annexin V (I-AnxV), a specific ligand of phosphatidylserine exposed by apoptotic cells, allows tissue detection of apoptosis in LPS-treated rat hearts. Heart I-AnxV uptake was significantly increased in all cardiac territories of LPS-treated rats.

Sequential 99mTc-hydrazinonicotinamide-annexin V imaging for predicting response to chemotherapy.

Unlabelled: This study was undertaken to evaluate changes in relative (99m)Tc-hydrazinonicotinamide (HYNIC)-annexin V tumor uptake over time in patients undergoing chemotherapeutic treatment at baseline and at 5-7 h and 40-44 h after treatment initiation. Imaging results are related to clinical outcomes, as assessed with response evaluation criteria in solid tumors (RECIST).

Methods: We prospectively included 20 patients (11 men and 9 women; mean age, 59.

In vitro screening for synergism of high-linear energy transfer 213Bi-radiotherapy with other therapeutic agents for the treatment of B-cell chronic lymphocytic leukemia.

Background: External beam radiotherapy and beta-radioimmunotherapy (RIT) are effective treatments for lymphoid malignancies. The development of RIT with alpha-emitters is attractive, owing to the high (LET) nature and short path length of alpha particles allowing for higher tumor cell kill and lower toxicity to healthy tissues.

Objectives: The aim of this study was to assess the response of B-Cell chronic lymphocytic leukemia (B-CLL) cells in vitro after treatment with chemotherapy (cisplatin, fludarabine, doxorubicin, or vincristine) or other pharmaceuticals (colchicine, simvastatin, or cyclosporin A) in combination with (60)Co-gamma or (213)Bi-alpha-irradiation.

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.

Evaluation of the antibacterial activity and toxicity of 2 new hydrogels: a pilot study.

Wound bed preparation remains a very important issue in wound healing. To promote the production of granulation tissue, it is necessary to remove necrotic tissue and to control infection. Necrotic tissue may be removed using a hydrogel preparation.

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.

Valine-based biphenylsulphonamide matrix metalloproteinase inhibitors as tumor imaging agents.

Among matrix metalloproteinases (MMPs), the subfamily of gelatinases (MMP-2, MMP-9) is of particular interest due to their ability to degrade type IV collagen and other non-fibrillar collagen domains and proteins such as fibronectin and laminin. Whilst malignant cells often over-express various MMPs, the gelatinases have been most consistently detected in malignant tissues and associated with tumor growth, metastatic potential and angiogenesis. Radiosynthesis of carboxylic (1') and hydroxamic (2') MMPIs resulted in radiochemical yields of 70 +/- 5% (n = 6) and 60 +/- 5% (n = 4), respectively.

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.

Tryptophane-based biphenylsulfonamide matrix metalloproteinase inhibitors as tumor imaging agents.

Aim: As a part of our efforts to use small organic matrix metalloproteinase (MMP) inhibitors with improved characteristics for the diagnosis and treatment of different kinds of tumor tissues, biphenylsulfonamide analogues were synthesized. This study reports on the in vivo biodistribution of iodine-123-labeled biphenylsulfonide and analogues in A549 lung carcinoma inoculated into athymic mice and the evaluation of their suitability as imaging agents using a single photon emission computed tomography (SPECT) camera.

Methods: The radioiodinated carboxylic and hydroxamic MMP inhibitors 2-(4'- [(123)I]iodobiphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionic acid (1') and 2-(4'-[(123)I]iodobiphenyl-4- sulfonylamino)-3-(1H-indol-3-yl)-propionamide (2') were synthesized by electrophilic aromatic substitution of the tributylstannyl derivatives.

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.

Small animal positron emission tomography during vagus nerve stimulation in rats: a pilot study.

Vagus nerve stimulation (VNS) is an effective neurophysiological treatment for patients with refractory epilepsy, however, the mechanism of action remains unclear. Small animal positron emission tomography (PET) permits the monitoring of biochemical processes during multiple scans in the same animal. The aim of this pilot study was to explore the potential of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG)-PET to investigate the effect of acute and chronic VNS on glucose metabolism in the rat brain.

In vitro and in vivo targeting properties of iodine-123- or iodine-131-labeled monoclonal antibody 14C5 in a non-small cell lung cancer and colon carcinoma model.

Purpose: The monoclonal antibody (mAb) 14C5 is a murine IgG1 directed against a yet undefined molecule involved in cell substrate adhesion found on the surface of malignant breast cancer tissue. mAb 14C5 is able to inhibit cell substrate adhesion and invasion of breast cancer cells in vitro. In normal tissues as well as in the stroma surrounding in situ carcinomas of the breast, no expression of the antigen 14C5 occurs.

In vitro and in vivo evaluation of [123I]-VEGF165 as a potential tumor marker.

One of the research challenges in oncology is to develop new biochemical methods for noninvasive tumor therapy evaluation to determine whether the chemotherapeutics is effective. Vascular endothelial growth factor (VEGF) was labeled with radioiodine and evaluated in vitro as well as in vivo, using A2058, a melanoma cell line overexpressing VEGFR-1 and -2. Saturation binding analysis with [(125)I]-VEGF resulted in a K(d) of 0.