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Biomedical subjects

J Clerc

Publications and source records attributed to J Clerc.

At least 19 recordsLinked to original sources
PubMed2005

A case of stunning of lung and bone metastases of papillary thyroid cancer after a therapeutic dose (3.7 GBq) of 131I and review of the literature: implications for sequential treatments.

Thyroid stunning is usually defined as the inhibition or suppression of iodide trapping by remnant thyroid tissue or by functioning metastases following a diagnostic dose of 131I. The risk of stunning increases progressively with larger doses. Because the threshold above which this effect occurs in thyroid remnants seems to be between 37 MBq and 111 MBq of 131I, therapeutic 131I doses of 3.7 GBq may cause stunning. We describe stunning of papillary thyroid cancer lung and bone metastases after a therapeutic dose of 131I (3.7 GBq). A T1 bone metastasis and bilateral lung metastases were diagnosed by post-therapeutic dose whole-body scan. Nuclear MRI detected another lesion at T4, whose 131I fixation was not obvious. An additional 0.7 GBq were given after recombinant TSH, 37 days after the therapeutic dose; 24 h later, uptake by the lung and T1 metastases had disappeared, but trapping was again seen 6 months later on the post-therapeutic scan. This re-appearance is evidence in favour of the transitory and reversible character of stunning, and confirms its correspondence to the decreased ability of viable thyroid cells to trap iodine and not to their destruction. A better understanding of stunning would make it possible, in the event of rapidly progressing disease and in conjunction with recombinant thyroid stimulating hormone (TSH), to give several therapeutic doses of 131I in close succession without each dose hampering the effectiveness of the subsequent one.

Adolescent↗
PubMed2001

SIMS evidence that carbimazole enhances spatial heterogeneity of thyroid iodine storage and targeting in a woman with Graves' disease.

Antithyroid drugs (ATD) are known to reduce 131I efficacy in thyrotoxicosis, though the underlying mechanism remains misunderstood. To study the impact of long term administration of carbimazole on both iodine stores (127I, secondary ion mass spectrometry microscopy) and targeting (125I, radioautography) at the intraglandular level in a woman who underwent surgery for Graves' disease. 125I distribution was dramatically heterogenous and large areas of the sample appeared poorly or no stained at all. This may correspond to flat follicles, hypofunctioning or ATD blocked ones and to the various histological changes related to the thyroiditis. SIMS counting showed huge variations of the interfollicular iodine stores (0 to 1.18 microg/mg) and lower mean values than those observed in nodular goiters. SIMS imaging depicted iodine free areas and others with preserved thyroglobulin synthesis, as assessed via 32S- mapping, but low to undetectable 127I, suggesting focal organification defects. Since ATD reduce iodine storage and uptake capabilities and enhance the iodine heterogeneity of interfollicular targeting, a related enhancement of the spatial 131I dose distribution is unavoidable. ATD may reduce 131I efficacy by variably reducing the number of follicles which can be actually or significantly targeted, e.g. irradiated (antirecruitement effect).

Antithyroid Agents↗
PubMed2000

Upper retropharyngeal node involvement in differentiated thyroid carcinoma demonstrated by 131I scintigraphy.

We report four patients with papillary thyroid cancer who had upper retropharyngeal node involvement demonstrated by 131I scintigraphy. Three patients presented with a thyroid nodule and enlarged jugular nodes. Total thyroidectomy was performed with node dissection. Pathology demonstrated papillary carcinoma with several metastatic nodes. 131I scanning 4 weeks after surgery demonstrated increased uptake in an upper retropharyngeal node. In one patient, thyroidectomy had been performed 21 years previously. Increased thyroglobulin level led to 131I scanning, which showed focal retropharyngeal uptake. All four patients had asymmetrical uptake at mouth level with focal uptake close to the sagittal plane. A lateral projection showed focal uptake between the base of the skull and the mandibular angle, behind the region of the mouth and nose. CT in all cases and MRI in one case confirmed the presence of an enlarged node. The mass was removed surgically in two patients and pathology confirmed the papillary nature of the metastatic node. Two patients were treated by 131I. Focal uptake of 131I in the region of the mouth is ambiguous, since salivary uptake of 131I is a common finding on scintigraphy. In cases of asymmetrical uptake in the region of the mouth, a lateral projection of the head therefore allows the correct diagnosis.

Adult↗
PubMed1998

Decreased uptake of therapeutic doses of iodine-131 after 185-MBq iodine-131 diagnostic imaging for thyroid remnants in differentiated thyroid carcinoma.

We performed a prospective random study to assess possible thyroid stunning by a 185-MBq iodine-131 dose used to diagnose thyroid remnants. Patients with differentiated thyroid carcinoma were included after total or near-total thyroidectomy. They were randomly assigned to two groups. In group 0 (G0, 32 patients), iodine-123 administration only was used to diagnose thyroid remnants and/or metastasis, so that no thyroid stunning by 131I would occur. In group 1 (G1, 19 patients), diagnostic imaging was performed with 123I and 185 MBq 131I. 123I imaging was less sensitive than 131I imaging in identifying thyroid remnants in both groups (94%). Thyroid uptake of 123I was measured in both groups (at 2 h) and was not significantly different between the groups. Patients with thyroid remnants who remained in the study (28/32 in G0, 17/19 in G1) were treated with 370 MBq 131I, 5 weeks after treatment (mean time, range 12-84 days). In 12/17 G1 patients thyroid uptake measurement was repeated immediately before treatment. Uptake was equal to 1.97% +/- 0.71% and significantly lower (P < 0.05) than the previous measurement (3.76% +/- 1.50%). Patients were imaged 7 days after administration of the therapeutic dose and the images were compared with the diagnostic images. In 28/28 G0 patients thyroid remnants were unchanged and clearly seen. In 5/17 G1 patients, however the remnants were hardly identified, although they had been clearly seen at the time of diagnosis. We conclude the following: (1) a diagnostic dose of 185 MBq 131I decreases thyroid uptake for several weeks after administration and can impair immediate subsequent 131I therapy; (2) 123I is slightly less sensitive than 131I in identifying thyroid remnants; and (3) the need to scan for thyroid remnants remains to be confirmed, since only 2/51 patients enrolled in this study were not treated with 131I.

Carcinoma, Papillary↗
PubMed1997

SIMS microscopy: methodology, problems and perspectives in mapping drugs and nuclear medicine compounds.

Secondary ion mass spectrometry (SIMS) microscopy, a mass spectrometry method designed in the 1960s, offers new analytical capabilities, high sensitivity (ppm to ppb region), high specificity and improved lateral resolution, thus facilitating insight into many physiological and biomedical questions. Apart from the sample preparation and the physical characteristics of the detection, the biological model must also be considered. SIMS analysis of diffusible ions and molecules requires strict cryogenic procedures which always begin by a flash-freeze fixation. Cellular integrity can be checked by mapping the major element distributions since intra and extracellular ions are redistributed only in damaged cells. Cryofixing may be followed either by a freeze-fracture methodology or by cryoembedding and dry-cutting. Chemical sample preparation is only used for ions or molecules bound to fixed cell structures. The use of scanning procedures ameliorates the lateral resolution and chromosome imaging has been reported with probe size of below 50 nm. Absolute quantification can be derived for embedded specimen by using internal references included in tissue equivalent resins. The sensitivity is limited by the ionization yield of the tag element and may be further impaired when working at high mass resolution (> or = 5000) to eliminate interfering cluster ions. SIMS drug mapping is usually performed after in vitro administration of a molecule to cell culture systems. Drug detection is accomplished indirectly by detecting a tag isotope naturally present or introduced by labelling, mainly with halogens, 15N and 14C. Molecular imaging with TOF-SIMS is an appealing alternative especially for heavier compounds. We stress some biological problems through a critical review of published SIMS drug studies. SIMS proved useful in assessing the targeting specificity of nuclear medicine pharmaceutics, even after in vivo administration. The first microscopic evidence of a thionamide induced follicular blockade of the iodine organification process is presented in a human sample.

Animals↗
PubMed1997

[131 iodine for the initial treatment of thyroid cancer].

Retrospective studies justified the use of 131 iodine after surgery in the management of thyroid cancer for reducing recurrences and improving survival. Indications based on the evaluation of prognostic factors and on the quality of surgical excision are more advisable than systematic administration, particularly in small, non aggressive tumors which are diagnosed more and more frequently. A high level of endogenous TSH and absence of iodine overload are required. Standardized fixed ablative doses reach a high rate of success. Various scintigraphic procedures allow precise localization of residual or distant uptake. Radioprotection measures must be carefully applied to the patients and their environment by a skillful personnel. Side effects are rare after one ablation dose but must be systematically noted and treated. Genetic and carcinogenetic risks are very low.

Combined Modality Therapy↗
PubMed1995

Assessing intratumor distribution and uptake with MBBG versus MIBG imaging and targeting xenografted PC12-pheochromocytoma cell line.

UNLABELLED: The heterogeneity of tumor uptake is likely to substantially limit the effectiveness of metaiodobenzylguanidine (MIBG) therapy. This study was done to establish whether metabromobenzylguanidine (MBBG) can target neuroendocrine tumors and to provide intratumor biodistribution and uptake information in comparison to MIBG. METHODS: MBBG and MIBG tumor uptake and kinetic studies were performed in experimental PC-12 pheochromocytoma grown in nude mice. Intratumor distribution studies were performed using autoradiography and secondary ion mass spectrometry (SIMS) microscopy, because the latter technique can detect and potentially quantify both drugs concomitantly within the same tumor specimen. RESULTS: MBBG uptake in PC12 tumors was early (2 hr) and intense (80% ID/g). Retention values were similar for both drugs 24 hr postinjection. At the cellular level, MBBG mostly accumulated in the cytosol. At the multicellular level, cells exhibited staining, but in many areas, SIMS images of both drugs were not spatially correlated. CONCLUSION: MBBG targeted experimental pheochromocytoma efficiently with high early uptake values. Bromine-76-MBBG is a promising means of imaging and quantifying tumor uptake with PET. Both drugs were localized in the cytosol, but the correlation between the two distributions, as assessed by the values of the standardized local concentrations, was weak although significant multicellularly.

3-Iodobenzylguanidine↗
PubMed1995

Radioiodine therapy of the autonomous thyroid nodule in patients with or without visible extranodular activity.

UNLABELLED: Patients with an autonomously functioning thyroid nodule (ATN) may be present with various clinical, biochemical and scintigraphic features. To optimize 131I dose planning and treatment timing in these patients, relationships between dosimetric data and clinical follow-up events must be established. METHODS: We retrospectively reviewed the records of 88 patients who received 131I (intended dose of 80 Gy) for an ATN, of whom 39 had evidence of extranodular activity (ENA) and 76 presented with overt thyrotoxicosis. In all of the patients, dosage calculation was monitored to estimate precisely both beta and gamma absorbed doses received by the ATN and the nodule-free lobe. The mean duration of follow-up was 75 mo (max 180) and always included biochemical thyroid tests. Finally, we compared the dosimetric profiles of four dosage schemes which had been normalized by simulation to ensure that the same absorbed dose threshold value was always delivered to the ATN. RESULTS: About 75% of the patients were cured at 6 mo for a mean 305 MBq administered. The absorbed doses delivered to the nodule-free lobe ranged from 12% (no ENA) to 86% (ENA) of the values delivered to the ATN, mainly in the form of beta irradiation. Life-table estimates for hypothyroidism and death were 9.6% and 22% at 75 mo, respectively. Hypothyroidism mainly developed in patients with nonsuppressed TSH levels but regardless of ENA, which often accounted for multifocal disease. CONCLUSION: We suggest that fixed doses bordering on 370 MBq are advizable in younger individuals and in patients with mild thyrotoxocosis, while 555 MBq-740 MBq can be administered in other patients and that ENA indicates multifocal autonomy in patients with toxic ATN and is a further indication for radioiodine treatment which should be begun as soon as possible to avoid the development of cardiac complications.

Aged↗
PubMed1994

Recent developments in medical applications of SIMS microscopy.

The purpose of this review is to present the recent developments in the medical applications of SIMS microscopy. This technique is one of the microanalytical mass spectrometry methods which allow in theory the detection of all the elements of the Mendeleiev table as well as the separation of stable and radioactive isotopes. It is based on a phenomenon whereby a biological sample surface is sputtered by bombardment with an energetic 'primary ion' beam. Part of the sputtered matter is ionized and the resulting 'secondary ions' are characteristic of the atomic composition of the analyzed area. These secondary positive or negative ions are collected and separated in a mass spectrometer at low or high mass resolution, which is dependent on both the element studied and its concentration. An analytic image which conserves the tissue distribution of the selected element is displayed on a fluorescent screen linked to an image processing system. Local elemental concentration can also be measured. Results are highly dependent on the techniques used for sample preparation which should preserve both the chemical and the structural integrity of the tissue. Further, the ionic images must be correlated with corresponding images of the same areas of the serial sections observed in a photonic microscope. With our SIMS microscope (lateral resolution approximately 0.5 microns, and mass resolution 300 to 12,000) we have demonstrated that this microscopic imaging technique is suitable for physiopathological studies. We revisited thyroid iodine metabolism by mapping chemical elements such as 32S and 127I, characteristic of hormonal physiology. Newly organified iodine (radioiodine) can be evaluated in relation to previously stored iodine (127I) in a given follicle, thus allowing an appraisal of glandular adaptation to aging and iodine overload. Another area in which SIMS can be used in medicine, is for the localization of drug markers in tumor tissue (e.g. fluorine-5-fluouracil, iodine in iododeoxyrubicin). This could facilitate the evaluation of the intratumor drug concentration at the onset of the treatment. Likewise, SIMS can be used to localize radiopharmaceuticals used in diagnosis (e.g. technetium) and therapy (131I of metaiodobenzylguanidine). This would permit a better evaluation of the radiation dose delivered to tissue. Further prospects are within reach with the imminent advent of higher lateral resolution (0.05 microns) SIMS microscopes.

3-Iodobenzylguanidine↗
PubMed1993

Comparison of the pharmacokinetics of methohexital during cardiac surgery with cardiopulmonary bypass and vascular surgery.

The aim of this study was to assess the pharmacokinetics of methohexital (ME) in major vascular surgery (VASC) and to compare these data with the pharmacokinetics of ME during hypothermic cardiopulmonary bypass (HCPB) (temperature: 28 degrees C) and normothermic cardiopulmonary bypass (NCPB) (temperature: 37 degrees C). An ME bolus (2 mg/kg) was administered to 8 VASC patients at the start of surgery and to 11 HCPB patients and 11 NCPB patients at the start of cardiopulmonary bypass (CPB). Twenty-one arterial blood samples were withdrawn over the following 24 hours for ME assays. All of the patients were given similar anesthesia (fentanyl, diazepam) and muscle relaxation (pancuronium). In the VASC group, ME total body clearance (TBC) was 6 +/- 2 mL/kg/min (mean +/- SD), which is less than in previous studies. When comparing HCPB and NCPB groups, elimination half-life (T1/2), TBC, volume of distribution (VD), area under the curve (AUC), and mean residence time (MRT) were similar. When comparing VASC and CPB patients, TBC and VD were greater in CPB patients than in VASC patients; thus, T1/2 (equal to 0.693 x VD/TBC) was similar. AUC was smaller in CPB patients because of hemodilution, but MRT was similar. It is concluded that ME clearance is lower in patients undergoing major vascular surgery than in healthy patients. The temperature and the duration of CPB do not seem to substantially influence the pharmacokinetics of ME when a bolus is administered. Parameters such as AUC, TBC, and VD appear modified by hemodilution during CPB; however, T1/2 and MRT, which allow comparisons between CPB and non-CPB patients, were similar in these patients.

Blood Proteins↗
PubMed1993

SIMS microscopy imaging of the intratumor biodistribution of metaiodobenzylguanidine in the human SK-N-SH neuroblastoma cell line xenografted into nude mice.

Microdosimetric evaluations of targeted radiotherapy of neuroblastoma with metaiodobenzylguanidine (MIBG) require precise assessment of the intracellular and intratumor distribution of the drug. We report the use of secondary ion mass spectrometry (SIMS) microscopy, a technique capable of mapping any chemical element within a biological specimen, to determine 127I-MIBG biodistribution in human neuroblastoma SK-N-SH xenografted into nude mice. Highly specific images of 127I-MIBG biodistribution were mapped within the tumor after in vivo administration of the drug and sample processing with cryotechniques (high-speed freezing and cryo-embedding), which prevent MIBG diffusion from original sites of uptake. We showed that the biodistribution of the tracer was highly nonuniform within the tumor. At the cellular level, most of the drug accumulated in the cytosol and perinuclear areas. In contrast, chemical sample processing provided not only a considerable loss in sensitivity due to passive diffusion of the drug in the organic solvents, but also artefactual images mainly due to MIBG redistribution onto the cell nuclei. Based on our findings in this SK-N-SH experimental tumor model, we suggest that MIBG should be attached to long-range emitters, in the hope of irradiating the many tumorous areas that remain carrier-free.

3-Iodobenzylguanidine↗
PubMed1993

Influence of dose selection on absorbed dose profiles in radioiodine treatment of diffuse toxic goiters in patients receiving or not receiving carbimazole.

We retrospectively reviewed the records of 224 patients with diffuse goiters treated with radioiodine, half of which received carbimazole. In all the cases, we carefully monitored the calculation of dosage. A lower percentage of early hypothyroidism but a higher failure rate was observed in the carbimazole subgroup. Nevertheless, after one year, a constant (4.5%) incremental rate of hypothyroidism was found regardless of carbimazole administration. Since we were able to precisely estimate the absorbed doses in our series, we evaluated by simulation the dosimetric profiles of nine methods of dose selection (MDS). These MDS were calibrated in such a way that the same threshold value of absorbed dose would always be reached at the thyroid level. We showed that the more elaborate the MDS, the more accurate the irradiation at the thyroid level and the lower the radiation dose administered. In patients not receiving carbimazole, a rapid MDS using modified early uptake measurements to predict the 24-hr actual value was found to be advisable. With patients receiving carbimazole and if a goal is to delay the occurrence of hypothyroidism, we advise MDS based on either a 48-hr uptake or on the calculation of the individual half-life.

Carbimazole↗
PubMed1993

Immunization by bovine thrombin used with fibrin glue during cardiovascular operations. Development of thrombin and factor V inhibitors.

Brief case histories of three patients aged 58, 38, and 44 years are reported. All underwent cardiovascular operations. Subsequently hemostasis test abnormalities developed between the seventh and eighth postoperative days after exposure to bovine thrombin used with fibrin glue. These were characterized by an increased activated partial thromboplastin time (64 to 147 seconds), prothrombin time (19 to 24 seconds), bovine thrombin time (> 120 seconds) and a markedly reduced factor V level (< 10% in two patients and 16% in the third patient). A patient plasma dilution of 1 in 200 with a normal plasma pool was necessary to correct bovine thrombin time. No fast-acting or progressive inhibitor against factor V could be detected by coagulation tests, and fresh frozen plasma perfusion had no effect. Plasmapheresis was performed preventatively to avoid bleeding, and factor V levels stabilized at around 50% after two to four exchanges. Immunologic studies showed that the inhibitors were directed not only against bovine factors but also against human ones. Therefore factor V decrease could have been the result of rapid clearance from the circulation of complexes formed with a nonneutralizing inhibitor that is not detected by clotting tests. These antibodies were purified by standard methods and immunoaffinity. Fast immunization could be explained by a prior sensitization to bovine thrombin exposure during previous operations. It is suggested that bovine thrombin used with fibrin glue contains small amounts of factor V and may be responsible for these abnormalities. This is in agreement with previous literature reports. However, these described neutralizing factor V inhibitors, which were easily detected.

Adult↗
PubMed1992

SIMS microscopy in the biomedical field.

We attempted to indicate the requirements for biomedical applications of SIMS microscopy. Sample preparation methodology should preserve both the structural and the chemical integrity of the tissue. Furthermore, it is often necessary to correlate ionic and light microscope images. This implies a common methodological approach to sample preparation for both microscopes. The use of low or high mass resolution depends on the elements studied and their concentrations. To improve the acquisition and processing of images, digital imaging systems have to be designed and require both ionic and optical image superimposition. However, the images do not accurately reflect element concentration; a relative quantitative approach is possible by measuring secondary ion beam intensity. Using an internal reference element (carbon) and standard curves the results are expressed in micrograms/mg of tissue. Despite their limited lateral resolution (0.5 microns) the actual SIMS microscopes are very suitable for the resolution of biomedical problems posed by action modes and drug localization in human pathology. SIMS microscopy should provide a new tool for metabolic radiotherapy by facilitating dose evaluation. The advent of high lateral resolution SIMS imaging (less than 0.1 microns) should open up new fields in biomedical investigation.

Animals↗