Biodistribution and pharmacokinetics of the alphavbeta3-selective tracer 18F-galacto-RGD in cancer patients.

(18)F-Galacto-RGD has been developed for PET of alpha(v)beta(3) integrin expression, a receptor involved in, for example, angiogenesis and metastasis. Our aim was to study the kinetics and biodistribution of (18)F-Galacto-RGD in cancer patients. METHODS: Nineteen patients with metastases of malignant melanoma (n = 7), sarcomas (n = 10), or osseous metastases (n = 2) were examined. After injection of 133-200 MBq (18)F-Galacto-RGD, 3 consecutive emission scans from the pelvis to the thorax or dynamic emission scans of the tumor over 60 min, followed by 1 static emission scan of the body, were acquired. Time-activity curves and standardized uptake values (SUVs) were derived by image region-of-interest analysis with image-based arterial input functions. Compartmental modeling was used to derive the distribution volume for muscle tissue and tumors. RESULTS: (18)F-Galacto-RGD showed rapid blood clearance and primarily renal excretion. SUVs in tumors ranged from 1.2 to 9.0. Tumor-to-blood and tumor-to-muscle ratios increased over time, with peak ratios of 3.1 +/- 2.0 and 7.7 +/- 4.3, respectively, at 72 min. The tumor kinetics were consistent with a 2-tissue compartment model with reversible specific binding. Distribution volume values were, on average, 4 times higher for tumor tissue (1.5 +/- 0.8) than those for muscle tissue (0.4 +/- 0.1). The data suggest that there was only minimal free and bound (specific or nonspecific) tracer in muscle tissue. CONCLUSION: (18)F-Galacto-RGD demonstrates a highly favorable biodistribution in humans with specific receptor binding. Most important, this study shows that (18)F-Galacto-RGD allows visualization of alpha(v)beta(3) expression in tumors with high contrast. Consequently, this tracer offers a new strategy for noninvasive monitoring of molecular processes and may supply helpful information for planning and controlling of therapeutic approaches targeting the alpha(v)beta(3) integrin.     

Chronic multifocal non-bacterial osteomyelitis in hypophosphatasia mimicking malignancy

Background  

Hypophosphatasia (HP) is characterized by a genetic defect in the tissue-nonspecific alkaline phosphatase (TNSALP) gene and predominantly an autosomal recessive trait. HP patients suffer from reduced bone mineralization. Biochemically, elevated concentrations of substrates of TNSALP, including pyridoxal-5'-phosphate and inorganic pyrophosphate occur in serum, tissues and urine. The latter has been associated with chronic inflammation and hyperprostaglandinism.     

The hazards to practitioners of obstetric and gynecological ultrasound.

OBJECTIVES: To investigate the specific complaints of physicians and technicians performing obstetric and gynecological ultrasound. METHODS: This was a cross-sectional retrospective survey. Questionnaires were distributed to members of the Israeli Society of Gynecological Ultrasound, including questions on gender and profession, number and type of scans performed, pain related to profession and any therapy undergone. Statistical analysis included chi-square or Fisher's exact test, Student's t-test, Pearson's correlation coefficient and logistic regression. RESULTS: Joint pain was reported by 51.7% (30/58) of the technicians compared with 25.3% (19/75) of the physicians (P = 0.002). It was more common in females than in males (P = 0.05) and it was more common among those who performed transabdominal sonography more frequently than they did transvaginal sonography (P = 0.004). There was a significant association between performing transabdominal ultrasound and back pain (P = 0.05). Although females reported pain more frequently, the rate of surgical procedures was higher among males (P < 0.05). CONCLUSIONS: A technician is 3.5 times more likely to report joint pain than is a physician. Transabdominal sonography is a risk for both joint and back pain. There may be gender differences in pain perception.     

Solitary ganglioneuroma of the rectum: report of two cases.

Two cases of solitary rectal ganglioneuromas are reported, one in a patient with several previously resected colorectal adenomas, the other in a patient with no known predisposing pathology. No prior reports of cases of solitary rectal ganglioneuroma have been published as far as is known, and the origin of similar lesions which have been reported at other sites in the gastrointestinal tract is a subject for speculation.     

Cellular Distribution of G Protein Goa in Pituitary Lactotrophs: Effects of Dopamine

Membrane-bound GTP-binding (G) proteins mediate signal transduction in a variety of cell systems. The exact mechanisms of G proteins action are still under investigation but they appear to involve effectors located in the plasma membrane as well as in other parts of the cell. With this study, we investigated the cellular and ultrastructural localization of G protein subunits, and particularly of Goa, in normal rat anterior pituitaries and in estrone-induced rat adenomatous lactotrophs. We also evaluated the effects of Goα cellular redistribution in rat adenomatous lactotrophs following short-term exposure to dopamine (DA). Using the Protein A-gold (PAG) methodology, Goα was found to be present in the cysternae of the endoplasmic reticulum of normal pituitary cells and of adenomatous lactotrophs. In the latter, Goα could be co-localized with prolactin (PRL). By immunoblots, using specific antisera, significant amounts of Goα and Gs42α, together with smaller amounts of Giα, Gs47α and Gβ were found to be present in the uncontaminated supernatant fraction of adenomatous lactotrophs. Unexpectedly, exposure of the cells to DA induced a rapid and short-lived decrease in the cytosolic fraction of Goα and Gβ associated with a decrease of PRL release. Since cytosolic Goα can be ADP-ribosylated by pertussis toxin (PT) and is therefore in a heterotrimeric form, our data suggest that the soluble Go protein may play a role during lactotrophs' exposure to an inhibitor of PRL release, perhaps through its relocalization after being internalized with the D₂ receptor or by being used for interaction with intracellular and/or membrane-bound effectors.     

Acute exacerbation of bronchial asthma in children associated with afternoon weather changes

We studied the effect of the weather on acute exacerbations of bronchial asthma in children by comparing records of 8,657 admissions for five acute respiratory diseases (3,064 for asthma) with concurrent meteorologic data. These diseases were classified according to their interrelations and distinct meteorologic patterns into two groups: (1) acute asthma and acute laryngitis, which are correlated with the afternoon gradients of air temperature, heat content (the thermal energy of the ambient air), and modified heat content factor (the energy required to heat the air water vapor to the ambient temperature), but not correlated with the absolute values of air temperature and water content: and (2), bronchopneumonia/pneumonia and upper respiratory infections, which are correlated only with the absolute values of the meteorologic parameters (air temperature, water content, heat content, and modified heat content factor), but not with their afternoon gradients. Admissions for bronchiolitis revealed an age-related pattern: up to 1 yr they resembled Group 2 and from 1 to 2 yr, Group 1. It follows that the admission rates of acute exacerbation of bronchial asthma in childhood are linked both to the afternoon weather gradients and to some of the acute respiratory infections.     

Retinoic acid induced heparin-binding protein expression and localization during gastrulation,neurulation, and organogenesis

Retinoic acid induced heparin-binding protein (RIHB) is a highly basic, soluble polypeptide of the chick embryonic extracellular matrix. We have examined the expression and localization of RIHB during very early embryogenesis by in situ hybridization and immunohistochemistry. RIHB mRNA is very weakly detectable above background in the blastodiscs of unincubated eggs. The expression increases greatly over the first 24 hours of incubation, and is observed throughout the blastodisc in all three of the germ layers following gastrulation. As neurulation occurs, the expression becomes more restricted to certain areas, notably the ectoderm, the neural folds, and especially the notochord. After the neural tube has formed the expression in the tube itself decreases dramatically, whereas the expression in the head ectoderm and the notochord persists. After 72 hours of incubation expression remains relatively high throughout most of the embryo, with higher levels of expression in regions undergoing organogenesis and lower levels in organs which have already differentiated. RIHB protein is also weakly detectable in unincubated eggs as patches of immunoreactive material between the blastodisc and the vitelline. After 6 hours of incubation small regions of basement membrane are immunoreactive. RIHB is detected in this matrix, apparently before even fibronectin. The amount of RIHB protein increases dramatically over the first 24 hours of incubation. It is found in basement membrane separating the epiblast from the hypoblast, then later in that separating the ectoderm from the mesoderm. It is also detected surrounding individual cells, especially of the ectodermal layer. During neurulation RIHB is observed in the basement membrane surrounding the neural fold and the notochord, and in the lamina separating the ectodermal, mesodermal, and endodermal layers. Later in development, RIHB is detected in the basement membrane under the epidermis, throughout the developing limbs, and in the lamina of various developing organs, such as the eye, the pulmonary bud, the intestine, and the mesonephros. These results demonstrate that RIHB is highly expressed during the early embryonic period, by all three germ layers, and is an important and very early component of the embryonic extracellular matrix. Its very broad expression and localization argue for a more general role in development than its demonstrated weak neurotrophic activity. © 1994 Wiley-Liss, Inc.     

Cardiotoxicity evaluation in patients treated with a mitoxantrone combination as adjuvant chemotherapy for breast cancer.

Indices of cardiac function were measured in 49 women who received adjuvant treatment for stage II breast cancer. The combination chemotherapy consisted of six monthly courses of cyclophosphamide, 500 mg/m2, mitoxantrone, 10 mg/m2 and fluorouracil, 500 mg/m2 (CNF). Left ventricular function was assessed by echocardiography, systolic time intervals and nuclear angiography. The values of the echocardiographic left ventricular end diastolic diameter (Dd) and end systolic diameter (Ds), and those of the index of preejection period (PEPI) and the ratio of the preejection period to left ventricular ejection time (PEP/LVET), determined in 41 patients before chemotherapy, at midcourse and after chemotherapy by echocardiography and systolic time intervals (STI), showed a slight but significant increase. All these values remained within normal limits. Resting nuclear angiography, performed before and after treatment, showed a decrease in LVEF by 10% or more in four patients; the postchemotherapy values remained within the normal range in all cases. In conclusion, adjuvant treatment of breast cancer patients with 6 cycles of the CNF combination, as judged by its effect on the measured indices, does not appear to be cardiotoxic.     

Hypointense transcerebral veins at T2*-weighted MRI: a marker of hemorrhagic transformation risk in patients treated with intravenous tissue plasminogen activator.

Prediction of hemorrhagic transformation (HT) in patients treated by intravenous recombinant tissue-type plasminogen activator (rt-PA) is a challenging issue in acute stroke management. HT may be correlated with severe hypoperfusion. Signal changes may be observed at susceptibility-weighted magnetic resonance imaging (MRI) within large perfusion defects. A signal drop within cerebral veins at T2*-weighted gradient-echo MRI may be expected in severe ischemia, and may indicate subsequent risk of HT. The authors prospectively searched for an abnormal visibility of transcerebral veins (AVV) within the ischemic area in patients with hemispheric ischemic stroke, before they were treated with intravenous rt-PA therapy. Any correlation between AVV and baseline clinical or MRI findings, or further HT, was noted. An AVV was present in 23 of 49 patients (obvious, n = 8; moderate, n = 15), and was supported by severe hemodynamic changes at baseline MRI. The AVV was correlated with the occurrence of parenchymal hematoma type 2 at computed tomography during the first week (r = 0.44, P = 0.002). Five of six type 2 parenchymal hematomas occurred in association with obvious AVV. At multiple regression analysis, two baseline MRI factors had an independent predictive value for HT risk during the first week: the AVV and the cerebral blood volume ratio (Nagelkerke R2 = 0.48).