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Biomedical subjects

P Lind

Publications and source records attributed to P Lind.

At least 145 records · Page 8Linked to original sources

Influence of human anti-mouse antibodies on thyrotropin in-vitro analysis: a comparison of 6 thyrotropin IRMA kits.

OBJECTIVE: The aim of the study was to evaluate the influence of human anti-mouse antibodies on the measurement of thyrotropin. INVESTIGATIONS: Samples from 11 patients with measureable human anti-mouse antibody titres (19 micrograms/l-3880 micrograms/l) after radioimmuno-scintigraphy were analysed with 6 different thyrotropin immuno-radiometric assay kits (IRMA). Each sample was analysed in the routine way (sample influenced by human anti-mouse antibodies), as well as after incubation with murine immunoglobulin to precipitate human anti-mouse antibodies (samples not influenced by human anti-mouse antibodies). RESULTS: Two kits showed clear deviations of measured thyrotropin levels when the human anti-mouse antibody titres were higher than 1350 micrograms/l. A third kit was influenced to a lesser extent by human anti-mouse antibodies. Three of the 6 investigated thyrotropin IRMA kits produced thyrotropin values that were unaffected by the presence of elevated human anti-mouse antibodies. In comparison with former studies after immunotherapy, the thyrotropin deviations were marginal. However, differences were found between the commercially available thyrotropin assays. According to the results of this study only three out of the six investigated kits were unaffected by human anti-mouse antibodies. CONCLUSION: Since thyrotropin is one of the key quantities for the endocrinologist dealing with the thyroid gland, every laboratory should ensure high quality thyrotropin assays by critically analysing their method for human anti-mouse antibody.

Adult↗

[Therapy of hypo- and hyperthyroidism in pregnancy].

Therapy of thyroid dysfunction needs a close cooperation between endocrinologist and gynecologist. In addition to a number of metabolic changes during pregnancy, the diaplacentar transfer of different substances (thionamides, antibodies) has to be considered. Pregnant women with overt and subclinical hypothyroidism should be treated using L-Thyroxine with the bTSH between 1 and 2 mU/l. Many of the women need an increase of the L-Thyroxine dose during pregnancy. Overt hyperthyroidism (mostly due to Graves' disease) has to be treated immediately after diagnosis using thionamides. Because thionamides cross the placenta, the dose should be as low as possible with the fT4 in upper level and bTSH in the lower level of normal range. Most studies show, that both methimazole (MI) and propylthiouracil (PTU) can be used in pregnancy. Although PTU is preferred especially in the USA, an advantage of PTU over MI is not proven. Surgery is necessary in only few cases of hyperthyroidism during pregnancy with the optimal time for surgery during the second trimester. In case of subclinical hyperthyroidism and HCG induced hyperthyroidism several controls of thyroid function should be performed to decide whether treatment is necessary.

Abnormalities, Drug-Induced↗

Molecular cloning and RNA expression of two new human chemokine receptor-like genes.

Two new human genes encoding putative G protein-coupled receptors were cloned from genomic DNA following a degenerate PCR strategy. The predicted amino acid sequences of the proteins encoded by these genes have the characteristic motifs of chemokine receptors. This prompted us to name these genes CKR-L1 and CKR-L3. Nevertheless, the identification of their ligands has not been possible using 16 human chemokines in three different assays. The RNA expression pattern of CKR-L1 and CKR-L3 is also similar to that generally found for chemokine receptors. To a different extent, these genes are expressed in spleen, lymph nodes, and CD4+, CD8+ and CD19+ lymphocytes. CKR-L1 expression was also detected in monocyte/macrophages. The homology to chemokine receptors suggests that CKR-L1 belongs to the family of beta chemokine receptors, while CKR-L3 is more similar to alpha chemokine receptors.

Amino Acid Sequence↗

Phenethylthiazolylthiourea (PETT) compounds as a new class of HIV-1 reverse transcriptase inhibitors. 2. Synthesis and further structure-activity relationship studies of PETT analogs.

Phenylethylthiazolylthiourea (PETT) derivatives have been identified as a new series of non-nucleoside inhibitors of HIV-1 RT. Structure-activity relationship studies of this class of compounds resulted in the identification of N-[2-(2-pyridyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea hydrochloride (trovirdine; LY300046.HCl) as a highly potent anti-HIV-1 agent. Trovirdine is currently in phase one clinical trials for potential use in the treatment of AIDS. Extension of these structure-activity relationship studies to identify additional compounds in this series with improved properties is ongoing. A part of this work is described here. Replacement of the two aromatic moieties of the PETT compounds by various substituted or unsubstituted heteroaromatic rings was investigated. In addition, the effects of multiple substitution in the phenyl ring were also studied. The antiviral activities were determined on wild-type and constructed mutants of HIV-1 RT and on wild-type HIV-1 and mutant viruses derived thereof, Ile100 and Cys181, in cell culture assays. Some selected compounds were determined on double-mutant viruses, HIV-1 (Ile 100/Asn103) and HIV-1 (Ile100/Cys181). A number of highly potent analogs were synthesized. These compounds displayed IC50's against wild-type RT between 0.6 and 5 nM. In cell culture, these agents inhibited wild-type HIV-1 with ED50's between 1 and 5 nM in MT-4 cells. In addition, these derivatives inhibited mutant HIV-1 RT (Ile 100) with IC50's between 20 and 50 nM and mutant HIV-1 RT (Cys 181) with IC50's between 4 and 10 nM, and in cell culture they inhibited mutant HIV-1 (Ile100) with ED50's between 9 and 100 nM and mutant HIV-1 (Cys181) with ED50's between 3 and 20 nM.

Animals↗

Comparison between persisting anti-lipopolysaccharide antibodies and culture at postmortem in salmonella-infected cattle herds.

Herds with recent clinical outbreaks of Salmonella dublin (7 herds) and S. typhimurium (4 herds) infections were followed serologically in O-antigen ELISAs over about one year, divided in four equal sampling phases. Animals found to be persistent high-reactors or seronegative at the end of the study were slaughtered and subsequently cultured for salmonella in a selected number of organ samples. Approximately 3% of all animals had high seroreactions up to 17 months after the outbreaks, and less than half of the seropositive animals in the S. dublin-infected herds were salmonella culture positive at slaughter (14/31). However, one persistently seronegative animal was also culture positive. Furthermore, as much as 70% of the male calves investigated at postmortem in the S. dublin-infected herds were high-reactors, among which approx. 56% were culture positive. Surprisingly, 2 of the 14 animals found culture positive turned out to be culture positive for S. typhimurium only. In the S. typhimurium study, none of the 17 animals investigated at postmortem were salmonella culture positive. All sera from these animals were negative in the O:9 blocking ELISA, and no serum sample was positive in the S. dublin ELISA, alone. In conclusion, although serology based on the O-antigens appears to be useful to identify salmonella-infected herds, it seems to be insufficient for identification of persistently infected animals.

Animals↗

Worm kinetics and serum IgE in hooded lister rats infected with the acanthocephalan Moniliformis moniliformis and the nematode Nippostrongylus brasiliensis.

After infection with the intestinal helminths Moniliformis moniliformis or Nippostrongylus brasiliensis, worm-specific IgE first appeared in the serum rats between days 10 and 24 p.i., varying with host age, worm species and worm dose used. The rate of increase in specific IgE was comparable regardless of the worm species, infection dose or host age and a peak response was observed about 1 month after the sera turned positive. In the M. moniliformis infections, these events took place long before the beginning of worm expulsion on day 63 in high-dose (50 worms) infections, and potentiation of heterologous IgE was not observed. In contrast, IgE stimulation by N. brasiliensis infections was detected as potentiation of anti-ovalbumin IgE, anti-M. moniliformis IgE and total IgE. Most of the total IgE in the serum of M. moniliformis-infected rats was likely to be the worm-specific IgE. Anthelminthic removal of M. moniliformis revealed that the presence of residual worms was necessary to maintain worm-specific IgE production.

Aging↗

Experimental single and trickle infections of cattle with Taenia saginata: studies of immunodiagnosis.

Two groups of 12 calves were given either a single infection dose of 30,000 Taenia saginata eggs (group A) or trickle infected with 12 x 2500 T saginata eggs (group B). The calves were killed 16, 22 or 54 weeks after infection and the numbers of viable and dead parasites were counted by slicing selected organs and muscles of half of the carcases. The total numbers of cysts and the numbers of viable cysts were higher in group A than in group B. Within the two groups there were no significant differences between the numbers of cysts at the three dates of slaughter. Comparable results were obtained by using an ELISA and a dot blot procedure for the detection of antibody in the serum of the infected calves; an initial increase in response during the first 10 weeks after infection was generally followed by a gradual decline. When using a monoclonal antibody-based ELISA for the detection of circulating antigens, the sera from all the 14 animals which had no viable cysts or only dead cysts at slaughter did not react with the monoclonal antibodies. Calves 122 and 123, which harboured two and 122 viable cysts, respectively, reacted positively during the late phase of the infection to the antigen-detecting ELISA. However, several other animals which harboured between two and 41 viable cysts at slaughter did not react.

Animals↗

Specific immunoglobulin measurements related to exposure and resistance to Schistosoma mansoni infection in Sudanese canal cleaners.

The present work comprises a longitudinal study of Schistosoma mansoni infection in occupationally hyper-exposed canal cleaners in the Sudan and the influence of chemotherapy on humoral immune parameters. The study groups included chronically infected canal cleaners (n = 19), newly recruited canal cleaners (n = 17), normally exposed adults (n = 31), school children (n = 46) and Sudanese negative controls (n = 48). Previous studies of the same canal cleaners have demonstrated that chronically infected canal cleaners were more resistant to reinfection than newly recruited canal cleaners. ELISA was used to detect specific IgE and IgG subclasses in response to whole worm antigen (WWH) and soluble egg antigen (SEA) before and 3 months after praziquantel treatment in the groups of canal cleaners and before and 1 year after treatment in normally exposed adults. When intensity of infection was correlated with IgE antibody response, the resistant group of canal cleaners (those who stopped passing ova after treatment) showed a significant positive correlation between intensity of infection and specific IgE to WWH (Spearman's correlation coefficient = 0.49, P < 0.05) compared with a highly significant negative correlation in the susceptible group (acquired new infection after treatment, Spearman's correlation coefficient = -0.94, P < 0.01). Normally exposed adults and school children had significantly less specific IgE to WWH than canal cleaners, while chronically infected canal cleaners had significantly higher levels of specific IgG1 to WWH than newly recruited canal cleaners and school children, and significantly higher levels of specific IgG4 to WWH than school children. There was a significant increase in specific IgG1 and IgG4 to WWH, 3 months after treatment, in newly recruited canal cleaners and a significant decrease, 1 year after treatment, in normally exposed adults. None of the groups studied after treatment showed a significant change in their specific IgE to WWH. Normally exposed adults had significantly lower levels of specific IgE to SEA than newly recruited canal cleaners, and significantly lower levels of specific IgG1 to SEA than other infected groups. Both newly recruited canal cleaners and school children had significantly higher levels of specific IgG2 to SEA than persons in other groups. Only small differences between groups were observed with regard to specific IgG3 and IgM to SEA. Specific IgG4 to WWH and SEA showed different patterns after treatment between the resistant and susceptible groups of canal cleaners. The resistant group maintained the same level of IgG4 to WWH after treatment compared with a significant increase in the susceptible group. On the other hand, levels of specific IgG4 to SEA showed a highly significant decrease after treatment in the resistant group. In contrast, the same antibody subclass increased after treatment in the susceptible group. Generally, results show an association between IgE and IgG1 responses to WWH and resistance to reinfection. In contrast, an association was observed between IgG2 and IgM responses to SEA and susceptibility to reinfection.

Adult↗

Use of a new glass microfibre histamine release method to study the modulation of the host response in human schistosomiasis mansoni. Individuals with different degrees of exposure to the disease show differing antibody biological function.

A new glass microfibre histamine release method was used to study the modulation of the host response in human schistosomiasis mansoni to improve our understanding of the role of basophils in the development of immunity in schistosomiasis mansoni. The histamine release from umbilical cord blood basophils sensitized with sera from Sudanese individuals infected with Schistosoma mansoni was measured. Schistosomiasis sera (n = 113) were able to passively sensitize basophils and induce a positive histamine release in response to whole worm homogenate (WWH) (chi 2 = 40.5, P < 0.0001) and soluble egg antigen (SEA) (chi 2 = 16.3, P < 0.0001). However, worm antigen induced significantly higher histamine release in adults than egg antigen (Z = 4.83, P < 0.0001). Basophil cell sensitivity to WWH was inversely related to the intensity of infection. A correlation was observed between basophil cell sensitivity and IgE antibodies in response to WWH. Chronically infected canal cleaners (n = 16) showed a significant increase in basophil cell sensitivity 3 months after praziquantel treatment (Z = 1.73, P < 0.05). Normally exposed adults (n = 29) showed a significant decrease in basophil cell sensitivity 1 year after treatment. When serum fractions were used, chronically infected canal cleaners showed a significant increase in histamine release after IgG removal (P < 0.05) Comparison between the different study groups with regard to resistance and susceptibility to reinfection, their basophil sensitizing ability and antibody response showed a difference in the biological function of the IgE to WWH in the different groups. Direct histamine release results from S. mansoni infected individuals from outside the endemic area (Danish) showed the possibility of using the glass microfibre histamine release method in the diagnosis of schistosomiasis.

Adult↗

Seroreactivity of Salmonella-infected cattle herds against a fimbrial antigen in comparison with lipopolysaccharide antigens.

The IgG seroreaction of Salmonella-infected cattle herds against a fimbrial antigen (SEF14) was compared with that against lipopolysaccharide (LPS) antigens. Sera from 23 dairy herds (n = 205) from an island with no occurrence of salmonellosis, four herds (n = 303) with recent outbreaks of S. dublin and four herds (n = 168) with recent outbreaks of S. typhimurium, were tested in a SEF14-ELISA, S. dublin LPS (0:1, 9, 12) ELISA and S. typhimurium LPS (0:1, 4, 5, 12) ELISA. At a cut-off OD of 0.5, only one of the animals tested from the salmonellosis-free island showed significant seroreaction against the SEF14 antigen, which was confirmed in a Western-blot analysis. Three out of the four S. dublin-infected herds had several seroreactors in the SEF14-ELISA, whereas all the four herds were positive in the 0:1, 9, 12-ELISA. All but two samples (both from the same herd) in the four S. typhimurium-infected herds, positive in the 0:1, 4, 5, 12-ELISA, had OD values below 0.5 in the SEF14-ELISA. The results indicate that cattle can produce detectable specific antibodies against fimbrial antigens which may be used for screening of S. dublin-infected herds, particularly in areas with low prevalence of salmonellosis, increasing the predictive value of serology.

Animals↗

Activity of antibodies against Salmonella dublin, Toxoplasma gondii, or Actinobacillus pleuropneumoniae in sera after treatment with electron beam irradiation or binary ethylenimine.

Viral contamination of biological material may constitute a risk when samples are exchanged between countries, and it may be necessary to subject the material to an inactivation treatment. The present study investigated possible adverse effects on antibody activity subsequent to either electron beam irradiation or binary ethylenimine (BEI) treatment. The treatments were performed with sera obtained from pigs or cattle. For each treatment level, the posttreatment activity was plotted against the pretreatment activity, and regression analyses were carried out. The slope of the regression line was used as an estimate for the relative posttreatment activity. For a Toxoplasma gondii indirect enzyme-linked immunosorbent assay (ELISA) and agglutination assay as well as for a Salmonella dublin indirect ELISA, the posttreatment activity was more than 89% of the pretreatment activity when the samples were irradiated in the frozen state (on dry ice) with up to 46. kGy or when they were treated with 5 or 10 mM BEI for up to 48 h. The samples were more sensitive to irradiation in the liquid state. Thus, samples irradiated with 22.6 kGy retained 98% of their activity in the indirect ELISA when they were irradiated in the frozen state on dry ice but only 35% of their activity when they were irradiated in the liquid state at 0 degrees C. The patterns seen in an S. dublin blocking ELISA and an Actinobacillus pleuropneumoniae complement fixation assay differed in that samples with a low level of pretreatment activity were subject to a relatively greater decrease in activity than samples with a high level of pretreatment activity. The complement fixation assay was particularly sensitive to irradiation of serum. It is concluded that serum samples retain sufficient activity by both methods of virus inactivation, especially when used in indirect ELISA or in the T. gondii agglutination assay.

Actinobacillus pleuropneumoniae↗

Toxicokinetics of 2,4- and 2,6-toluenediamine in hydrolysed urine and plasma after occupational exposure to 2,4- and 2,6- toluene diisocyanate.

OBJECTIVES: To assess the toxicokinetics of 2,4- and 2,6- toluenediisocyanate (TDI) in chronically exposed subjects. METHODS: Blood and urine, from 11 workers at two flexible foam polyurethane production plants, were sampled. By gas chromatography-mass spectrometry (GC-MS) 2,4- and 2,6-toluene diamine (TDA) were measured as pentafluoropropionic anhydride (PFPA) derivatives after acidic hydrolysis of plasma (P-TDA, ng/ml) and urine (U-TDA, microgram/h). RESULTS: In one of the plants the P-2,4-TDA concentrations were 0.4-1 ng/ml before a four to five week holiday and 0.2-0.5 ng/ml afterwards. The corresponding values for P-2,6-TDA were 2-6 and 0.5-2 ng/ml respectively. In the other plant the P-2,4-TDA concentrations were 2-23 ng/ml before the holiday and 0.5-6 ng/ml afterwards and the P-2,6-TDA concentrations were 7-24 ng/ml before and 3-6 ng/ml afterwards. The P-2,4-TDA concentrations were 2-24 ng/ml before a 12 day holiday, and 1-14 ng/ml afterwards. The corresponding values for P-2,6-TDA were 12-29 and 8-17 ng/ml, respectively. The urinary elimination rates (U-TDA, microgram/h) for 2,4-TDA before the holiday were 0.04-0.54 and 0.02-0.18 microgram/h afterwards. The corresponding values for 2,6-TDA were 0.18-0.76 microgram/h before and 0.09-0.27 microgram/h after the holiday. The half life in urine ranged between 5.8 and 11 days for 2,4- and 2,6-TDA. The differences in exposure were reflected by the P-TDA concentrations. The mean half life in plasma was 21 (range 14-34) days for 2,4-TDA and 21 (16-26) days for 2,6-TDA. The TDI air concentrations varied between 0.4 and 4 micrograms/m3 in one plant and in the other between 10 and 120 micrograms/m3. CONCLUSIONS: The half life in plasma of chronically exposed workers for 2,4-and 2,6-TDA was twice as long as for volunteers with short term exposure. An indication of a two phase elimination pattern in urine was found. The first phase was related to the more recent exposure and the second, much slower one was probably related to release of TDA in urine from TDI adducts in the body.

Air Pollution↗

Immunohistochemical diagnosis of systemic bovine zygomycosis by murine monoclonal antibodies.

Murine monoclonal antibodies (Mabs) against water-soluble somatic antigens (WSSA) and the wall fraction (WF) from Rhizopus arrhizus (Rhizopus oryzae) were produced in vitro by fusion of splenocytes from immunized BALB/c mice with mouse myeloma X63-Ag 8.653 cells. Supernatants reacting only with homologous antigens in an enzyme-linked immunosorbent assay were subsequently screened for reactivity with homologous fungi in immunohistochemical techniques. All four Mabs raised against the WF of A. arrhizus failed to react on tissues. However, four of the Mabs raised against the WSSA of R. arrhizus (Mab-WSSA-RA-1 through Mab-WSSA-RA-4) revealed a high homologous reactivity on tissues and the cross-reactivity of these were subsequently evaluated on tissues containing other members of the family Mucoraceae and other unrelated fungi. On tissues and on immunoblots all four Mabs reacted identically and specifically with members of the family Mucoraceae, i.e., Absidia corymbifera, R. arrhizus, and Rhizomucor pusillus. The Mabs were all isotyped as IgM antibodies, were nonprecipitating, and reacted with homologous antigens with molecular masses from I4 to 110 kDa. With WSSA from A. corymbifera and R. pusillus the four Mabs were bound to antigens from 14 to 52 kDa and from 20 to 28 kDa, respectively. The diagnosis of 145 bovine lesions obtained by one of the specific Mabs (Mab-WSSA-RA-1) were compared to results obtained by heterologously absorbed polyclonal antibodies. In most lesions (n = 140 [approximately 97%]) the Mab and the polyclonal antibodies reacted in a similar pattern, i.e., positively for zygomycosis in 89 lesions, negatively in 41 aspergillosis lesions, and negatively in 10 undiagnosed lesions. Hyphae within two of four lesions in lymph nodes, which were not stained by the polyclonal antibodies, reacted with the specific Mab. However, in another three lesions of lymph nodes stained by the polyclonal antibodies no reactivity was seen with the Mab-WSSA-RA-1. The immunoreactivity of the Mabs (Mab-WSSA-RA-1 through Mab-WSSA-RA-4) raised against WSSA of R. arrhizus justify their application for the in situ diagnosis of systemic bovine zygomycosis.

Animals↗

Development of murine monoclonal antibodies for the immunohistochemical diagnosis of systemic bovine aspergillosis.

Murine monoclonal antibodies (MAbs) against water-soluble somatic antigens (WSSA) and the wall fraction (WF) from Aspergillus fumigatus were produced by fusion of splenocytes from immunized BALB/c mice with mouse myeloma X63-Ag 8.653 cells. The supernatants of in vitro cultured hybridomas were initially screened for reactivity with the WSSA and the WF from A. fumigatus and WSSA of other fungi in an enzyme-linked immunosorbent assay (ELISA). Supernatants reacting only with A. fumigatus antigens were subsequently screened for homologous and heterologous reactivity with immunohistochemical techniques using formalin-fixed, paraffin-embedded tissues from experimentally infected mice. Because of a high immunohistochemical reactivity with homologous fungi, 4 MAbs raised against A. fumigatus WSSA and WF were selected for a further evaluation of cross-reactivity (diagnostic specificity) in immunohistochemical and immunoblotting assays. In immunohistochemical assays, all MAbs raised against WSSA cross-reacted heavily with a number of other fungal species. All 4 MAbs (MAb-WF-AF-1-4) raised against the WF reacted strongly with hyphae of Aspergillus spp.; hyphae of Scedosporium apiospermum were also strongly labeled by MAb-WF-AF-3 and -4. The 2 specifically reacting MAbs (MAb-WF-AF-1 and -2) were of the IgM biotype and were precipitating, and in immunoblotting experiments both bound to a 106-kD antigen of the WF, whereas they did not bind to WSSA of A. fumigatus. One of the 2 aspergillosis-specific MAbs (MAb-WF-AF-1) was used to screen 145 mycotic lesions of cattle. The diagnoses on bovine lesions obtained by MAb-WF-AF-1 were compared with results based on reactivity with heterologously absorbed polyclonal antibodies and, for some lesions, to culture results. In the vast majority of lesions (n = 133), the MAb-WF-AF-1 and the polyclonal anti-Aspergillus antibodies reacted in a similar pattern, i.e., positively in 41 aspergillosis lesions and negatively in 92 zygomycotic lesions. Hyphae in 3 of 12 lesions that were not stained by the polyclonal antibodies reacted with the specific MAb-WF-AF-1; i.e., aspergillosis was diagnosed. The characteristics of the 2 MAbs (MAb-WF-AF-1 and -2) raised against the WF of A. fumigatus in ELISA and immunoblotting and immunohistochemical assays justify their application for the in situ diagnosis of systemic aspergillosis of cattle.

Animals↗

The use of non-specific tracers in the follow up of differentiated thyroid cancer: results with Tc-99m tetrofosmin whole body scintigraphy.

Since many years TI-201, as non-specific tumor-searching radionuclide, plays a certain although somewhat controversial role in the follow-up of differentiated thyroid carcinoma (DTC). Recently some Tc-99m labeled myocardial perfusion agents were introduced, that might be more important for nuclear oncology in the future. Aim of this study was to evaluate prospectively the reliability of the new non-specific tumor searching tracer tetrofosmin (Myoview) in the post operative follow-up of differentiated thyroid carcinoma during TSH suppressive thyroid hormone treatment and to compare the results in patients with metastasizing DTC to Tc-99m sestamibi (Cardiolite) and TI-201. In a pilot study 12 patients with elevated thyroglobulin (Tg) levels of more than 10 ng/ml and known metastatic disease were examined under TSH suppressive L-Thyroxine treatment comparing TI-201, Tc-99m sestamibi and Tc-99m terofosmin whole body scintigraphy (WBS). Furthermore in 146 consecutive follow up patients tetrofosmin WBS was performed under TSH-suppressive L-T4 treatment. The results were compared to serum thyroglobulin (Tg), ultrasonography (US) of the neck, I-131 whole body scintigraphy (I-131 WBS), transmission computed tomography (TCT) or magnetic resonance imaging (MRI) and bone scintigraphy. Whole body scans were performed with TI-201 (74 MBq; 20 min post injection), Tc-99m sestamibi (370 MBq; 20-60 min post injection) and Tc-99m tetrofosmin (370 MBq; 20-60 min post injection). Tumor/background ratios and optional time/activity analyses (up to 120 min post injection) were evaluated using the region of interest approach. In the pilot study tetrofosmin showed the highest T/BG ratios and detection rates (T/BG: 1.76 +/- 0.345) followed by TI-201 (T/BG: 1.59 +/- 0.396) and sestamibi (1.51 +/- 0.31 p = 0.05). From the 146 patients investigated consecutively with Tc-99m tetrofosmin WBS for the routine follow up of DTC, 88 patients (no thyroid remnants, no history of metastases or tumor recurrence) were tumor free. All of them resulted in negative Tc-99m tetrofosmin WBS. Another 32 patients (papillary carcinoma pT1) were also in complete remission, but had sonographically proven remnants (echonormal). Twenty one of them exhibited certain Tc-99m tetrofosmin accumulation in the thyroid bed. In 9 cases with local recurrence as confirmed by histopathology after reoperation or by cytology after fine needle aspiration, the tetrofosmin scintigraphy clearly revealed relapse of malignancy including 2 patients with tetrofosmin positive additional distant metastases. Seventeen patients had distant metastases (11 pulmonary, 3 bone, 2 bone and pulmonary, 1 bone and soft tissue) detected by different modalities and resulting in a total of 44 lesions to be evaluated. In the 23 radioiodine negative metastases, 17 were also detected by tetrofosmin (74%). In the 21 radioiodine accumulating lesions 19 were Tc-99m tetrofosmin positive (90%). Four cases with radioiodine negative disseminated lung metastases showed diffuse pulmonary tetrofosmin uptake. This prospective study shows that Tc-99m tetrofosmin is a new promising tracer to detect malignant recurrence and distant metastases in the follow up of DTC without the necessity of thyroid hormone withdrawl, especially in patients with elevated Tg level and no iodine uptake. Tc-99m tetrofosmin shows slight advantages concerning T/Bg Ratio, background clearance, detection rate and dosimetry compared with TI-201 and Tc-99m sestamibi.

Adenocarcinoma, Follicular↗