Radiobiological effect of 99mTechnetium-MIBI in human peripheral blood lymphocytes: ex vivo study using micronucleus/FISH assay.

99mTc-MIBI is currently used, for cardiac investigations, for parathyroid thyroid imaging and evaluation of various tumours. It has been demonstrated that 99mTc-MIBI is specifically taken up by the human peripheral blood lymphocytes (HPBL), cells which are known to be highly radiosensitive. To evaluate the possible chromosomal damage induced on HPBL by their in vitro exposure to increasing activities of 99mTc-MIBI and also to establish whether HPBL undergo apoptosis or necrosis after in vitro exposure to 99mTc-MIBI. Blood from two healthy donors were irradiated, incubated in vitro with increasing activities of 99mTc-MIBI corresponding to absorbed doses ranging from 1 microGy, 100 microGy, 1 cGy, 10 cGy, 50 cGy to 1 Gy. The cytokinesis block micronucleus (MN) assay was used and the frequency of binucleated cells (BN) with MN (MNBN) was analyzed in cultured HPBL (in either the G0- or G1- and S1-phase of the cell cycle). The fluorescence in situ hybridization (FISH) with pancentromeric probes was also applied to study the MN regarding whole chromosomes or acentric fragments. Apoptosis induction by 0.1 Gy of 99mTc-MIBI in HPBL was quantified using annexin-V test. The frequencies of MNBC were similar in control cultures and in HBPL cultures exposed to 1 microGy, 100 microGy and 1 cGy. However, they were significantly higher (P<0.05 versus controls and lower doses) after one treatment exposure to 0.25 mCi of 99mTc-MIBI (corresponding to 10 cGy) or more but the percentages of MNBN with 10 cGy, 50 cGy and 1 Gy did not differ significantly. The increase of MNBN was more pronounced (P<0.05) for cells irradiated during G1 phase than for those irradiated during G0 or S1. Using FISH, 80-90% of the MN were centromere negative. Although small, the absolute number of MN positive for centromeric signal and presumably containing whole chromosomes increased with doses. There is a statistically significant (P=0.001 and 0.006) increase of both apoptotic cells and necrosis, respectively, as compared to control cells in two times studied (24 and 36 h). Chromosomic damages can thus be demonstrated in HPBL after in vitro exposure of blood to at least 0.25 mCi of 99mTc-MIBI corresponding to one absorbed dose of 10 cGy, and for this dose, apoptosis and necrosis phenomenons were detected.

[Quid Nunc? The relationship between the medical world and society in Belgium and in Europe of the 25 at the dawn of the 21st century]. / Quid Nunc? La relation entre le monde médical et la société en Belgique et dans l'Europe des vingt-cinq à l'aube du XXIe siècle.

Since about twenty-five years, we observe important transformations of the socio-economic structures of our society, modifying the main references which reign over the social structures and thus over the medical world. As a result, we observe a social syndrome which we can define as a divorce between the medical world and the society. The consequences of this phenomenon can constitute a real danger for the whole society; nevertheless, actually we can still consider that Belgium can assure a very high level of medical care for the greatest part of the population for a really social prize. The main "clinical signs" of this divorce are mentioned and analyzed, the deeper reasons of them as well. Among them, we cite the recent law about the quite exclusive rights of the patients, an incoherent legislation concerning medical activities, the hostility of the world of media against the physicians, the insuffiencies to finance health care and the attacks against several medical organizations and--at least--the fact to give more and more preference to the non-scientific parallel medicine. This whole social process should be kept back because this divorce is not only an economical problem, but rather a question of humanism and of social culture.

Contralateral internal mammary node invasion in breast cancer: lymphoscintigraphic data.

Contralateral internal mammary (IM) node invasion has been analyzed in 1025 patients where the two IM chains have been investigated by lymphoscintigraphy. Contralateral IM lymphoscintigrams (LySc) were classified as abnormal (nodes involved by metastatic cancer) in 153 cases (or 15.6% of the population) and this included one-third of the cases with homolateral IMLySc abnormalities (114/318). Overall, patients with bilateral abnormalities on IMLySc (Grp A) had a similar survival to those with homolateral abnormal IMLySc (Grp B). However, when other prognostic variables were taken into account and two matched groups were obtained, patients with bilateral internal mammary node involvement had a highest incidence of clinically evident systemic metastatic disease than patients with homolateral IM involvement. Contralateral IM nodes are invaded in one-third of the cases with homolateral IM node invasion. These patients may have a prognosis worse than those with only homolateral IM disease.

[Nuclear accidents and iodine prophylaxis. Part 1: Risks due to irradiation of the thyroid gland]. / Accidents nucléaires et prophylaxie par l'iode. 1ere Partie: Risques liés à l'irradiation de la glande thyroïde.

In the frame of the emergency procedures in the case of an accident in a nuclear plant, this paper presents a survey of the information available on the risks related to the irradiation of the thyroid gland. Attention is focused on thyroid cancer resulting from an exposure to radioactive isotopes of iodine and especially and iodine-131. The consequences of the medical exposures as well as of the Hiroshima and Nagasaki irradiations are recalled first. Then the recently available informations on the effects on the populations exposed after the Tchernobyl accident are analysed more in details. Ten years after the accident, the most striking and the least questionable effects is a significant increase of the incidence of differentiated thyroid cancer in children, in the areas most exposed to the initial radioactive clouds. Young children are particularly vulnerable to this type of cancer which is of aggressive nature and shows a short latency period. These observations justify an iodine prophylaxis for the populations living in the vicinity of nuclear plants. Special attention should be paid to the protection of young children.

Tumor type and vascularity: important variables in infusional brachytherapy with colloidal 32P.

PURPOSE: This study investigated the role of histologic tumor characteristics, in comparison with a normal tissue, and of tumor vascularization on the uptake and retention of colloidal 32P used in infusional brachytherapy of solid cancers. The cytotoxicity of colloidal 32P was also evaluated for two tumors of different radiosensitivity, a melanoma, and a squamous cell carcinoma. METHODS AND MATERIALS: An in vitro analysis of colloidal 32P uptake was carried out on a human melanoma cell line, HBL, a human squamous cell carcinoma, SCC1, and normal fibroblasts, F-NBB. Tumor retention of colloidal 32P was studied in vivo for the HBL and the SCC1 tumors implanted subcutaneously in nude mice. Tumor vascular density was determined by microscopic study of Masson's trichrome slides of HBL and SCC1 tumors of about 1 cm diameter. RESULTS: In vitro studies showed that the time required for maximal cell uptake of colloidal 32P was only 10-20 min for the SCC1 and HBL tumors, while it took at least 60 min for the fibroblasts. After intratumoral injection of macroaggregated albumin (MAA), followed by 50 microCi of colloidal 32P, Bremsstrahlung imaging performed at 6 and 24 h showed that the activity remained in the HBL tumor while some of the radiocolloids leaked from the SCC1 tumor and was trapped in the reticuloendothelial system of the liver. Organ activity counting confirmed this finding: 32P activity was three to four times higher in the HBL than in the SCC1 tumor, whereas the activity in the liver, insignificant in the HBL mice (less than 0.1 microCi/g), was as high as 24 microCi/g in the SCC1 mice. This phenomenon may be explained by the difference in tumor vascular density, estimated for the HBL to be about four times less than that of the SCC1 tumor (5.7 vs. 21.4 blood vessels per mm2 for the HBL and the SCC1 tumors, respectively). CONCLUSION: Intratumoral infusion of colloidal 32P may be a useful complement of radiation therapy in the treatment of nonresectable but accessible solid tumors. Tumor vascularization must be taken into account for a successful vascular blockade by MAA prior to the infusion of colloidal 32P.

In vivo characterization by means of digital cell image analysis of early-induced fractionated radiotherapy effects on the MXT mouse mammary tumor.

PURPOSE: To study the cell kinetics and chromatin modifications occurring in function of the fractionated irradiation administered to the MXT mouse mammary adenocarcinoma. METHODS AND MATERIALS: The MXT tumor cells were submitted to three fractions of a 4.8 Gy dose delivered at 24-h intervals. MXT tumor cells were collected by means of fine needle aspirations (between 5 and 10 samples were obtained after each irradiation) during treatment and submitted to the computer-assisted microscope analysis of Feulgen-stained specimens. Three groups of parameters has been described: i.e., the geometry of the nucleus, the nuclear DNA content, and the chromatin texture. Furthermore, cell cycle parameters were studied in the aim to know the distribution of the cells within the cell cycle. RESULTS: The mean values relating to geometric parameters (i.e., the nuclear area and its standard deviation) decreased during treatment. Variations in the nuclear DNA content appeared as being cyclical and could be explained in terms of the modifications in the distribution of the cells within the cell cycle. The quantitative analysis of the cell cycle parameters revealed that the percentage of S cells increased regularly after each irradiation. In contrast, the percentage of G2 cells decreased between each irradiation. The parameters describing nuclear texture showed regular variations between each irradiation. These variations consisted in two cycles constituted by a decrease in chromatin condensation, followed by an increase. CONCLUSIONS: The development of the geometric parameters indicates that fractionated radiotherapy leads to the emergence of a more homogeneous population. The effects of the radiotherapy on the distribution of the cells within the cell cycle could be explained through the phenomenon of repopulation and by the high degree of radiosensitivity of the G2 cells (decrease in the percentage of G2 cells). Last, the variations observed at chromatin pattern level could be explained through DNA repair processes.

[Exposure to ionizing radiation: radiobiological and pathogenic effects (2)]. / Exposition aux rayonnements ionisants: effets radiobiologiques et pathogénie (2éme partie).

The present paper describes the radiobiological effects induced by an exposure to ionizing radiation and their pathogenesis. The different skin reactions are described in detail because of their importance and frequency. Thus the acute skin lesions after high doses and the late effects resulting, either from high doses, or from accumulation of chronic irradiation, are studied. The main early syndromes are then characterized: neurological, gastro-intestinal, bone-marrow and prodromic. As far as the complex problem of radiocarcinogenesis is concerned, the main results derived from studies by international organizations such as the ICRP and the UNSCEAR are reported: risk coefficient of 5% per gray, for lethal radioinduced cancer, after total body irradiation, at low dose of low-LET radiation. The effects of irradiation in utero are then considered: risk of malformation after irradiation during the two first months of pregnancy and risk of mental retardation after irradiation during the third and the fourth months. Finally, the genetic risk is presented as being equal to one fourth of the risk of carcinogenesis at low doses. The effects of irradiation on the gonads are also described.

[Exposure to ionizing radiation: radiobiological effects and pathogenesis. 1]. / Exposition aux rayonnements ionisants: effets radiobiologiques et pathogénie (1re partie).

The present paper describes the radiobiological effects induced by an exposure to ionizing radiation and their pathogenesis. The different skin reactions are described in detail because of their importance and frequency. Thus the acute skin lesions after high doses and the late effects resulting, either from high doses, or from accumulation of chronic irradiation, are studied. The main early syndromes are then characterized: neurological, gastro-intestinal, bone-marrow and prodromic. As far as the complex problem of radiocarcinogenesis is concerned, the main results derived from studies by international organizations such as the ICRP and the UNSCEAR are reported: risk coefficient of 5% per gray, for lethal radio-induced cancer, after total body irradiation, at low dose of low-LET radiation. The effects of irradiation in utero are then considered: risk of malformation after irradiation during the two first months of pregnancy and risk of mental retardation after irradiation during the third and the fourth months. Finally, the genetic risk is presented as being equal to one fourth of the risk of carcinogenesis at low-doses. The effects of irradiation on the gonads are also described.

Radioimaging of human breast carcinoma xenografts in mice by [123I]-labeled Z-17 alpha-iodovinyl-11 beta-chloromethyl-estradiol.

Z-17 alpha-iodovinyl-11 beta-chloromethyl-estradiol (Z-CMIV), a new selective estradiol derivative, can easily be labeled with high efficiency by radioactive iodine isotopes. Biodistribution studies and quantitative scintigraphic imaging of human breast carcinoma xenografts in mice demonstrated continuous and selective accumulation of the [123I]Z-CMIV, in estrogen receptor (ER)-positive target tumors, with significantly high target/nontarget ratio up to 48 h post-injection. A receptor-mediated mechanism of concentration of Z-CMIV in target tissues was confirmed by scintigraphic imaging and by biodistribution studies.

[Emergency measures in accidental exposure to ionizing radiation]. / Mesures d'urgence en cas d'expositions accidentelles aux rayonnement ionisants.

The present paper is intended to provide any physician with a basic information and recommendations on how to behave with individuals who have been irradiated and/or contaminated (or believed to have been exposed), either in the case of a broad nuclear accident or a limited accidental exposure (e.g. occupational). Emphasis is put on the emergency measures to be taken as well as on their relative priority. Information is also provided in order to allow any physician to assess the magnitude and the severity of the exposure on the basis of early clinical symptoms and reactions. This would enable him to sort out the patients and to orientate them towards the appropriate specialized centre, or on the other hand, to reassure the patients. The information and recommendations are presented, purposely, in a concise and schematic way in order to facilitate, when needed, a quick and easy reading.

[Role of radioactive iodine in the treatment of differentiated thyroid cancer: physiopathological basis, results, considerations from the viewpoint of radioprotection]. / Place de l'iode radioactif dans le traitement du cancer thyroïdien différencié: bases physiopathologiques, résultats, considérations du point de vue de la radioprotection.

Postoperative radioiodine treatment of differentiated thyroid cancer occupies a well determined place in the treatment policy of this disease. When the external exposure rate (EER) was determined at 1 m from the patient, 72 h after the administration of the high 131-I dosis, respectively 34 and 56 patients among 80 treated cases presented, and require external help for their daily life (+/- 90% of all cases). This value could be considered as the selective limit in order to authorize them to leave the hospital when favorable socio-economical conditions exist at home.

Labelled polycyanoacrylate nanoparticles for human in vivo use.

Isobutyl and isohexyl cyanoacrylate nanoparticles are used as drug carriers, particularly for some anti-cancer drugs. Body distribution as well as pharmacokinetics have been well studied in animal and partially in man. Labelling of the monomer itself or of the carried drug with beta-emitters allowed such studies. In man, however, organ distribution and uptake could easily be done and followed by means of scintigraphy (imaging) techniques if one could achieve nanoparticle labelling with gamma-emitting isotopes. We have developed labelling methods able to supply such carriers using gamma-emitters like radioactive iodine (125I or 131I), indium or technetium. We used DTPA as a spacer in order to fix the last two isotopes. This would mean that any other gamma-emitting cation can theoretically be tried pending on its ability to be chelated by DTPA. The preparations were obtained with high labelling yields, usually > 80% and were relatively stable in human plasma over the whole period of investigation. 111In and 99mTc labelled forms have been administered to rabbit and then to man with 60-75% accumulation in the reticulo-endothelial system.