Study of the labeling of two novel RGD-peptidic derivatives with the precursor [99mTc(H2O)3(CO)3]+ and evaluation for early angiogenesis detection in cancer.

In the initial stages of tumor formation, overexpression of integrins identifying the RGD sequence (Arg-Gly-Asp) is observed. The aim of the present study was the synthesis and labeling of two novel RGD derivatives, via the precursor [99mTc(H2O)3(CO)3]+, as well as the radiochemical and radiopharmacological evaluation of the labeled products. The labeling led to the formation of a single product in each case (>98%), with noteworthy in vitro stability, fast blood clearance and elimination by the hepatobiliary and the urinary systems.     

Prolactin,growth hormone and insulin-like growth factor-l in newborn children of smoking mothers*

OBJECTIVE Since maternal smoking causes fetal circulatory abnormalities, as well as disturbances of the maternal endocrine equilibrium, we measured the PRL, hGH and insulin-like growth factor-l (IGF-I) concentrations in the cord and venous blood of neonates of smoking mothers to determine whether or not the tobacco smoke affects the endocrine status of the neonate. DESIGN The above hormones were measured in the cord blood of the newborns of both smoking and non-smoking mothers. Also, PRL and hGH were determined at 24 and 72 hours after birth in newborns of both groups. PATIENTS Fifty-three newborns of smoking and 47 newborns of non-smoking mothers were investigated. Seventeen of the newborns of the smoking and 21 of the nonsmoking mothers were preterm. The remainder were full-term. MEASUREMENTS PRL was measured with a solid-phase immunoradiometric assay, hGH with a solid-phase two-site immunoradiometric assay and IGF-I with a solid-phase radioimmunoassay after extraction with acid-etha-nol. RESULTS The median value of PRL in the 17 preterm newborns of smoking mothers was 4941 mU/l (range 1322-7230), whereas in the 21 preterm newborns of nonsmoking mothers it was 2013 mU/l (range 243-4740) (P = 0 0002). The median hGH value in the above subjects was 1020 mU/l (range 35 2-208 4) and 59 8 mU/l (range 11 6-134-2), respectively (P = 0 0039). The median IGF-I was 580 7 U/l (range 253 2-4851 1) and 530 6 U/l (range 239 6-3591 5), respectively (P = 0 429). In the 36 full-term newborns of smoking mothers the median PRL value was 5171 mU/l (range 2074-7530), whereas in the 26 full-term newborns of non-smoking mothers it was 5081 (range 244-6540) (P = 0 048). The median hGH was 69 6 mU/l (range 42 3-280 0) and 32 2 mU/l (range 6 2-200 0), respectively (P = 0 0031). Also, the median IGF-I value was 926 3 U/l (range 348 5-5344 7) and 462 1 U/l (range 250 2-1578 7), respectively (P = 00024). On the 3rd day the PRL in the preterm neonates of both smoking and non-smoking mothers showed the same 16-5% drop, and thus the difference between the groups was maintained. A similar reduction in the hormone levels was observed in the full term neonates. CONCLUSIONS The findings indicate that the maternal tobacco-smoking causes disturbances of the endocrine status of the fetus, as shown by the increased levels of PRL, hGH and IGF-I, which are more pronounced between 30 and 37 weeks of gestation than at term.     

Immunolocalization of transitional cell carcinoma of the bladder with intravesically administered technetium-99m labelled HMFG1 monoclonal antibody

The aim of this study was the immunolocalization of transitional cell carcinoma of the bladder with a radiolabelled murine tumour-associated monoclonal antibody and the measurement of the absolute uptake of the antibody by the tumour. Fourteen patients with transitional cell carcinoma of the bladder received 3–6 mCi (111–222 MBq) of technetium-99m labelled HMFG1 monoclonal antibody intravesically and one patient, 2 mCi (74 MBq) of iodine-131 labelled 11.4.1, which is a non-tumour-specific monoclonal antibody. Four of the 15 patients were evaluated with singlephoton emission tomography (SPET) 1 1/2 to 2 h post administration. All patients underwent transurethral resection of the bladder tumour within 12–20 h following intravesical administration of the radiolabelled antibody. The radioactivity of biopsy specimens from normal urothelium and tumour areas were counted in a gamma counter. The mean uptake of the radiolabelled antibodies from normal and tumour sites was expressed as a percentage of the administered dose per kilogram of tissue. Conventional histology and immunohistochemistry using HMFGI monoclonal antibody were performed on paraffin sections of the biopsy specimens. Although our results are preliminary, it can be concluded that: (a) bladder tumours are well imaged by SPET when using^99mTc-HMFG1; (b) intravesically administered radiolabelled antibody remains on the bladder tissue and does not escape into the systemic circulation; (c) the wide range of tumour uptake values (0%–9.3% administered dose/kg) observed probably can be attributed to heterogeneity of the antigenic expression of the tumour; (d) values of^99mTc-HMFGI monoclonal antibody uptake by the tumour do not justify future attempts at radioimmunotherapy.     

Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant

The elimination, disposition and protein binding of ibuprofen (IBU) in premature infants were studied for use in the prevention of intraventricular hemorrhage and closure of patent ductus arteriosus. The kinetic profile of i.v. IBU lysine (10 mg/kg bolus) given within the first 3 h after birth was studied in 21 premature neonates (mean birthweight = 944.7 g, range: 575–1450 g; gestational age: 26.8 weeks, range: 22–31 weeks). Blood samples (0.3 ml/sample) were obtained at time 0 and at 1, 3, 6, 12, 24, 48, and 72 h post-dose for IBU by high-performance liquid chromatography (HPLC). Kinetic analyses assumed applicability of one open-compartment model and calculations from the model-independent areas under the time concentration curve (AUC). Data (mean ± SEM) show that apparent volume of distribution (AVd) was 62.1 ± 3.9 ml/kg, plasma t _1/2 beta was 30.5 ± 4.2 h, elimination rate constant (k_el) was 0.032 ± 0.004 h^-1plasma clearance was 2.06 ± 0.33 ml/kg/h and plasma concentration (Cp) at 1 h was 180.6 ±11.1 mg/1. Gestational age and birthweight were not related to drug elimination. In 10 neonates, IBU maintenance dose of 5 mg/kg once daily on days 2 and 3 generated mean Cp of 116.6 ± 54.5 mg/1 and 113.6 ± 58.2mg/1, respectively. Protein binding by ultrafiltration and capillary electrophoresis showed that the percentage bound IBU was significantly lower in full term cord plasma (94.98 ± 0.39%, n = 26) compared to adult plasma protein (mean ± SE = 98.73 ± 0.31%, n = 8, p < 0.0001). Compared to data from adults and older children, IBU elimination is markedly prolonged in neonates and protein binding is slightly lower. Thus, investigational and clinical therapeutic regimens should be adjusted to account for decreased drug disposition to ensure safe and effective therapy.     

Technetium labeled bombesin-like peptide: preliminary report on breast cancer uptake in patients

Bombesin-like peptides are neurotransmitters and cancer growth factors. Several tumors, breast cancer among them, show one or more than one of the three known bombesin receptors. We have synthesized and labeled with technetium 99m a new pentadecapeptide, analogue to the leu13 amphibian bombesin (99mTc BN). Labeling yield was 83 +/- 4%. Prone Scintimammography was performed on five patients affected by breast cancers (T categorization: two T1b and three T1c), after injecting 0.7 mg, 185 to 296 MBq (5 to 8 mCi) of the peptide. Total body scan did not show free technetium biodistribution. No adverse reaction was observed. Prone Scintimammography with 99mTc Sestamibi (99mTc SM) was also performed few days later. 99mTc BN detected all 5 cancers, whereas 99mTc SM only four: all the T1c and one T1b cancer. Two of them showed axillary node invasion that was detected by both the radiotracers. A fibroadenoma present on contralateral breast to the one with cancer, was not detected neither by 99mTc SM nor by 99mTc BN. Tumor/breast normal tissue ratio (T/B) was constantly higher with 99mTc BN than with 99mTc SM. Maximal T/B was measured as 1.79 with 99mTc SM and 2.25 with 99mTc BN 5 min after fast i.v. administration. In conclusion our 99mTc BN is taken up by primary breast cancer showing higher T/B than 99mTc SM (p < 0.01). In our limited scale, 99mTc BN appears to be safe and, in our limited scale, even more accurate than 99mTc SM for detecting breast cancer.     

Employer-Mandated Sleep Apnea Screening and Diagnosis in Commercial Drivers

INTRODUCTION:: Obstructive sleep apnea (OSA) is common among commercial drivers and associated with health/safety risks, leading several trucking firms to mandate OSA screening. METHODS:: A total of 19,371 commercial drivers were screened for OSA with an online questionnaire (Somni-Sage) through employer mandates. Questionnaire and polysomnography results were analyzed retrospectively. RESULTS:: Screening categorized 5908 drivers (30%) as higher risk. To date, employers have sent 2103 higher-risk drivers for polysomnography, demonstrating that 68% of high-risk drivers tested had an apnea-hypopnea index (AHI) greater than 10 and 80% had an AHI of 5 or more. A conservative prevalence estimate for OSA (AHI > 10) was 21% among the drivers studied. CONCLUSIONS:: Online screening followed by polysomnography for high-risk drivers demonstrates as many as 21% of commercial drivers may have OSA. Mandatory screening can have a high yield among commercial drivers.     

Fast cancer uptake of 99mTc-labelled bombesin (99mTc BN1)

In human blood, breakdown of gastrin-releasing peptide and other bombesin-related peptides occurs in less than 15 min. This quick enzymatic cleavage might impair the diagnostic use of labelled bombesin (BN). 99mTc-labelled bombesin (99mTc BN1) was injected intravenously and dynamic uptake data were acquired for diagnosing 26 cancers of different origin: 15 breast, 3 prostate, 5 colo-rectal, 1 pancreas, 2 small cell lung cancers and 1 gastrinoma. Background subtracted tumour uptake data were plotted against time and fitted with known mathematical functions. Twenty-three out of 26 cancers showed rapid increase of radioactivity followed by a radioactivity plateau, with some oscillations around the average plateau value. The time to 80% of max activity (T80) was the reference parameter to measure and to compare the uptake speeds. The slowest T80 was 7 min in one T1b breast cancer, gastrinoma reached T80 in 5 min and node-positive prostate cancers in 2 min. N+ breast cancers showed T80 at 3.62 +/- 0.75 min, N- breast cancers at 5.5 +/- 0.88 min (p < 0.02). When all the tumours were considered, N+ tumours showed T80 at 2.68 +/- 1.03 min and N- cancers at 5.5 +/- 0.82 min. In all the cancer types, the uptake of 99mTc BN was faster than 10 min. This result shows the ability of 99mTc BN to image tumours. The faster uptake by N+ versus N- cancers probably depends on the higher blood flow in N+ cancers.     

Increased cortisol concentrations in the cord blood of newborns whose mothers smoked during pregnancy

AIM: To investigate the effect of tobacco smoke on cord blood cortisol concentrations. METHODS: Cortisol concentrations were measured in cord blood from 211 term newborns of smoking and 211 term newborns of nonsmoking mothers; 48 and 36 newborns were delivered by cesarean section, respectively. In 16 cases, in addition to cord blood, maternal venous blood was obtained at delivery. RESULTS: The median cord blood cortisol concentration in neonates of the smoking and the nonsmoking mothers was 23 and 13 microg/dL, respectively (P<0.0001). Cortisol concentrations were greater in the newborns whose mothers smoked, when compared to corresponding controls, whether they were delivered vaginally or by cesarean section. In the newborns delivered by cesarean section, there was a positive correlation between number of cigarettes smoked/day and cortisol concentrations, as well as a negative correlation between cortisol concentrations and neonatal length. There was no significant correlation between cortisol concentrations and birth weight or head circumference. Cortisol concentrations in the cord blood of neonates whose mothers were smokers and nonsmokers were by 29% and 45% lower from those measured in their mothers, respectively. CONCLUSIONS: Although a causal relationship between maternal smoking and high cortisol concentrations in cord blood was not established, the findings are in accordance with previous reports indicating elevated stress-hormones in newborns whose mothers smoked during pregnancy.     

Specified systems of high spatial resolution for tomographic gamma cameras; their applications and studies in Greece

Imaging with nuclear medicine planar and tomographic gamma cameras, offers information about the function of an organ, the detection and the delineation of a lesion. However, the basic limitations of these cameras are low statistics, the significant noise (background), the relatively low spatial resolution and low sensitivity. Moreover, commercially available systems are large, since they are constructed for general clinical use only and so, small organs such as brain, heart, breast, prostate etc cannot be efficiently imaged. For these reasons a number of dedicated imaging systems have been developed, based on modifications of the existing technology or on novel technology. One important limitation in using such systems routinely is their high cost. The most important applications of these new systems are focused on imaging small animals or small human organs, on scintimammography, on sentinel node detection and for the evaluation of new radiopharmaceuticals. In the present work, the principles of operation of these dedicated SPET imaging systems, results from clinical trials and present Greek studies, are presented.