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Biomedical subjects

J Michelot

Publications and source records attributed to J Michelot.

At least 19 recordsLinked to original sources
PubMed2001

Synthesis, characterization and comparative biodistribution study of a new series of p-iodine-125 benzamides as potential melanoma imaging agents.

Iodobenzamides are reported to possess some affinity for melanoma. In order to identify the compound having the most appropriate pharmacokinetic properties as a potential melanoma imaging agent, thirteen new [125I]radioiodobenzamides with a butylene amide-amine spacer and various substituents on the terminal amino group were investigated. Their synthesis, radioiodination and biodistribution in B16 melanoma bearing C57BL6 mice are described and compared to [125I] labeled N-(2-diethylaminoethyl)-4-iodobenzamide ([125I]BZA), our reference compound. Changes in the terminal amino constituents induced modifications of lipophilicity, tumor uptake and organ distribution. The dimethylaminobutyl iodobenzamide appeared to be the most promising radiopharmaceutical imaging agent for the detection of melanoma and its metastases.

Animals↗
PubMed2001

Distribution of I-BZA (N-2-diethylaminoethyl-4-iodobenzamide) in grafted melanoma and normal skin: a study by secondary ion mass spectroscopy.

Iodobenzamides labelled with radioactive iodine are undergoing clinical evaluation as imaging and potential therapeutic agents in malignant melanomas. However, the uptake mechanism in melanic tissues remains controversial. Using secondary ion mass spectrometry (SIMS), we studied the microscopic distribution of N-(2 diethylaminoethyl)-4 iodobenzamide (I-BZA) in B16 murine melanoma inoculated to C57BL/6J1 Co mice as well as in normal pigmented skin. SIMS provides specific detection of iodine-127 atoms entering 127I-BZA composition. In B16 melanoma, 127I-BZA distribution was found to be heterogeneous, with focal areas of high concentration corresponding to cells rich in melanin pigments. In skin, SIMS analysis showed 127I-BZA distribution appearing as multiple small selective concentration areas within the epidermis. The number of these foci decreased from the stratum basale towards the stratum corneum. In both tissues, the intracellular location appeared specifically intracytoplasmic, with no apparent nuclear uptake. Distribution of this molecule mirrored that of melanin pigments. There was no enhancement of uptake at the membrane site. These results suggest that, in melanic tumors as well as in normal pigmented tissue, specific uptake of 127I-BZA occurs in pigment cells, with a possible link to melanin pigments.

Animals↗
PubMed2000

Establishment of IPC 227 cells as human xenografts in rabbits: a model of uveal melanoma.

This study was designed in order to evaluate the feasibility of establishing an animal model of human uveal melanoma. IPC227, a cell line established from the biopsy of a patient with a spindle cell ciliary body melanoma, was transplanted into the anterior chamber of the eye in immunosuppressed New Zealand rabbits. In a second step, a tumour fragment from the anterior chamber was implanted transclerally into the posterior choroid. Complete ophthalmological examinations were then performed on the animals. Characteristic growth patterns were noted depending on the location of implantation. In the anterior chamber, diffuse, flat, heavily pigmented tumours appeared 8 days after the injection of the cell suspension that covered the iris and the angle by day 25, with a success rate of 100%. Nodular, lightly pigmented tumours were obtained 6-7 weeks after subchoroidal implantation, with a 25% success rate. Clinical examination, including fundus photography, ultrasound and magnetic resonance imaging, demonstrated the same characteristics as those of human uveal melanoma, confirming the value of this model for the evaluation of new therapeutic and diagnostic methods in the management of uveal melanoma.

Animals↗
PubMed1998

Clinical study of [123I] N-(2-diethylaminoethyl)-4-iodobenzamide in the diagnosis of primary and metastatic ocular melanoma.

PURPOSE: To assess the value of scintigraphy with [123I]N-(2-diethylaminoethyl)-4-iodobenzamide (BZA), a phase II clinical trial was performed on 48 patients with a suspicion of ocular melanoma. METHODS: 56 examinations were performed to image lesions with a clinical diagnosis of primary ocular melanoma before and/or after treatment, to observe the results in simulating lesions or to image metastases. RESULTS: Ocular BZA-scintigraphy demonstrated a sensitivity of 86%, and a specificity of 83%. Whole-body scintigraphy was used in the follow-up of treated patients and could be repeated. We imaged orbital recurrence, known and occult metastases, specially in the liver. After 9 conservative treatments ocular BZA-scintigraphy was negative in 9 eyes. CONCLUSION: The BZA-scintigraphy in combination with other diagnostic procedures appeared to be a suitable method in the diagnosis of ocular melanoma and a potentially useful imaging modality to screen for ocular malignant melanoma metastases.

Adolescent↗
PubMed1996

Application of textural features to the detection of ocular melanomas in scintigraphy.

A method for automated detection of ocular melanoma in scintigraphic images is described. The algorithm first performs an automatic segmentation of the eyes on specific reference images. The images of the eyes are then analyzed using textural parameters computed in several directions and averaged to damp directional information. Assuming that only one eye per patient will be pathological, the ratio of the textural parameters of the two eyes is computed. A statistical analysis is performed over these ratios to select the most highly discriminating textural parameters and detect the pathological patients. The method has been tested successfully on a population of 23 individuals and we found significant differences between pathological and normal patients.

Algorithms↗
PubMed1996

Localization of N-(2-diethylaminoethyl)4-iodobenzamide in the pigmented mouse eye: a microanalytical study.

The 123I-N-(2-diethylaminoethyl)4-iodobenzamide (123I-BZA) is a new radiopharmaceutical used for the scintigraphic imaging of malignant melanomas. The mechanism for BZA uptake in melanic tissues is still unknown. Two methods of microanalysis, secondary ion mass spectrometry and electron probe X-ray microanalysis, were used to determine tissue distribution and subcellular location of unlabelled BZA in the C57BL6/J1 co mouse eye. Microanalysis showed elective BZA uptake by the pigmented structures of the eye: choroidal melanocytes and retinal pigment cells, where it was specifically located within melanosomes. The tropism of BZA for melanic tumours, as well as for normal pigmented tissues, could be explained by a high affinity for the melanin pigment.

Animals↗
PubMed1995

Synthesis, radiolabeling, and preliminary evaluation in mice of some (N-diethylaminoethyl)-4-iodobenzamide derivatives as melanoma imaging agents.

N-(2-Diethylaminoethyl)-4-iodobenzamide (BZA) is a radiopharmaceutical recently developed in our laboratory for the scintigraphic detection of melanoma and metastases. Optimal time for imaging was between 18-24 h p.i. of [123I] BZA. With a view to selecting compounds able to provide quality images shortly after the injection, synthesis of an initial series of BZA derivatives and their evaluation in B16 melanoma bearing mice have been carried out. The [125I] radiolabeled products were obtained by a simple isotopic exchange procedure with high radiochemical yields (85-95%). After i.v. administration of the compounds we observed a good tumoral targeting ability. Tumoral activity peaked at 2.6 to 7.70% injected dose per g within 1 h post-injection. One of the benzamides with a blood clearance faster than that of BZA--0.06 vs. 0.2% I D/g--6 h p.i. gave the same tumor to blood and to organ ratios as BZA at 12-18 h p.i. Based on these preclinical data we hope to obtain good tumoral images 6 h p.i. in scintigraphic studies in man.

Animals↗
PubMed1993

In vitro uptake of technetium-99m-teboroxime in carcinoma cell lines and normal cells: comparison with technetium-99m-sestamibi and thallium-201.

Since 201Tl, 99mTc-sestamibi and 99mTc-teboroxime concentrate in cardiac cells through different mechanisms, we compared their uptake in cultured normal cells and carcinoma cell lines in order to define their possible use for tumor evaluation in vivo. Four lines of normal cells from animals, including myocytes from newborn rats, and four lines of human carcinoma cell lines were incubated for 1 hr with 37 kBq of either tracer. Results, expressed in percent of the total activity taken up by 1 million cells, showed a 9% difference between the uptake of teboroxime by normal and carcinoma lines (24.6% +/- 2.8% versus 22.5% +/- 2.1%, respectively, p < 0.05). Mean uptake was 80% higher in tumor than in normal cells for 201Tl (5.39% +/- 1.33% versus 3.00% +/- 1.08%, respectively, p < 0.001) and nearly 4 times higher for sestamibi (5.37% +/- 2.34% versus 1.44% +/- 1.88%, p < 0.001). For both agents, uptake by the myocytes and carcinoma cells was comparable (5.14% +/- 0.11% for 201Tl and 5.28% +/- 1.03% for sestamibi). When the myocytes are excluded from the group of normal cells, the uptake is 112% higher in tumor than in normal cells for 201Tl (5.39% +/- 1.33% versus 2.54% +/- 0.44%, p < 0.001) but it becomes nearly nine times higher for sestamibi (5.37% +/- 2.34% versus 0.60% +/- 0.23%, p < 0.001). It is concluded that these experiments show that the uptake of sestamibi was the most discriminant to separate between normal and malignant cells, while teboroxime was the less discriminant. Potential clinical applications for tumor visualization based on differences in sestamibi and teboroxime uptake could be envisioned.

Animals↗
PubMed1990

[Perspectives of scintigraphic diagnosis of malignant lymphoma using a new radiopharmaceutical].

In the sequence of our studies on radiopharmaceuticals for malignant melanoma detection the results were most promising for the possible use of 125I or 123I-N-(2-diethyl amino ethyl)4-iodobenzamide. The biodistribution in mice bearing melanoma either human or animal from 4 to 24 hrs. post i.v. injection showed high uptake in tumor tissue together with relatively low uptake in muscle, brain, lung and liver. Scintigraphic images of the tumor obtained at the same times confirmed that melanoma detection was very promising.

Animals↗
PubMed1985

IgG purification to measure the level of an iodinated thyroglobulin peptide, the 3,5,3',5' tetraiodo-l-tyrosyl-l-tyrosine in human serum.

Antibodies reacting with 3,5,3',5' tetraiodo-l-tyrosyl-l-tyrosine (I2Tyr-I2Tyr) were elicited in rabbits by immunization with an oxidized yeast conjugate coupled with I2Tyr-I2Tyr. Ion-exchange chromatography was used to purify immunoglobulins, in order to improve the specificity in measurement of I2Tyr-I2Tyr level in patient serum. IgG binding capacity versus I2Tyr-I2Tyr was considerably increased after immunoglobulin purification.

Animals↗
PubMed1982

Metabolism of adiphenine. II. Identification of major excretion metabolites in rats.

1. Major metabolites isolated from rat urine after administration of a single dose of [14C]adiphenine or [3H]adiphenine were identified by chromatography and n.m.r. spectrometry, and by comparison with authentic reference compounds chemically synthesized. 2. Adiphenine was extensively metabolized by hydrolysis of the ester bond into diethylaminoethanol, diphenylacetic acid, diphenylacetic acid glucuronide and, in small quantities, the corresponding glycine and glutamine conjugates.

Animals↗
PubMed1981

Metabolism of adiphenine. I. Absorption, distribution and excretion in rats and mice.

1. The disposition of adiphenine labelled with 14C in two positions has been investigated in rats and mice after i.v. administration, and has been compared with that of the [14C]diethylethanolamine HCl and of the [14C]diphenylacetic acid. 2. Radioactivity in the blood declined in a biphasic manner. Biliary elimination depended upon the 14C-labelled compound administered: less than 5% dose for the diethylethanolamine moiety, 100% dose for the carboxylic moiety. Of the radioactivity appearing in rat bile, less than 1% is associated with unchanged adiphenine. 3. In preliminary metabolic studies, three major metabolites have been identified: diphenylacetic acid, diethylethanolamine and a diphenylacetic acid glucuronide. 4. Uptake by the brain of [14C]adiphenine shortly after dosing is 15 times greater than that of blood. Radioactivity is also found in the hypophysis, the adrenals and melanoid pigments, with a concn. up to 30 times greater than that found in the blood.

Absorption↗
PubMed1979

[Autogenous ovary grafts in rabbits. Experimental study (author's transl)].

The authors report the techniques used and the results obtained in a experimental study of autogenous ovary grafts in rabbits. The various methods of control--histological, hormonal and isotopic--used to measure the vitality of the grafts, showed their good quality. Active ovarian tissue was found to be present within the graft: 17 beta-oestradiol and progesterone secretion was demonstrated by means of radio-immunological plasma dosages and LH fixation in the ovarian tissue graft was shown by means of 131 iodine. This recovery was however accompanied by a loss of ovarian functional potential and chances of impregnation and gestation were reduced due to a strong peritoneal reaction.

Animals↗
PubMed1975

[In vitro biosynthesis of iodothyronines from diiodo-3,5-L-tyrosyl-diiodo-3,5-L-tyrosine (author's transl)].

A comparative study of two types of in vitro synthesis of iodothyronines has been done from 3,5-diiodotyrosine and from diiodo-3,5-L-tyrosyl-diiodo-3,5-L-tyrosine (Tyr(I)2-Tyr(I)2) (equimolecular in tyrosyl rings). Incubations are made with rat thyroid gland minces in Eagle's medium or with thyroid microsomal fraction. Synthesis of thyroid hormones from Tyr(I)2-Tyr(I)2 is faster and more important than from diiodo-3,5-L-tyrosine (Tyr(I)2). A mechanism of iodothyronine formation via Tyr(I)2-Tyr(I)2 and different from the one occuring for Tyr(I)2 is suggested.

Animals↗