Purpose: Immuno^positron emission tomography (PET), the combination of PET with monoclonal antibodies (mAb), is an attractive option to improve tumor detection and to guide mAb-based therapy. The long-lived positron emitter zirconium-89 ( 89 Zr) has ideal physical characteristics for immuno-PET with intact mAbs but has never been used in a clinical setting. In the present feasibility study, we aimed to evaluate the diagnostic imaging performance of immuno-PET with 89 Zr-labeled-chimeric mAb (cmAb) U36 in patients with squamous cell carcinoma of the head and neck (HNSCC), who were at high risk of having neck lymph node metastases. Experimental Design: Twenty HNSCC patients, scheduled to undergo neck dissection with or without resection of the primary tumor, received 75 MBq 89 Zr coupled to the anti-CD44v6 cmAb U36 (10 mg). All patients were examined by computed tomography (CT) and/or magnetic resonance imaging (MRI) and immuno-PET before surgery. Six patients also underwent PET with 18 F-fluoro-2-deoxy-D-glucose. Immuno-PETscans were acquired up to 144 hours after injection. Diagnostic findings were recorded per neck side (left or right) as well as per lymph node level (six levels per side), and compared with histopathologic outcome. For this purpose, the CT/MRI scores were combined and the best of both scores was used for analysis. Results: Immuno-PETdetected all primary tumors (n = 17) as well as lymph node metastases in 18 of 25 positive levels (sensitivity 72%) and in 11of 15 positive sides (sensitivity 73%). Interpretation of immuno-PET was correct in 112 of 121 operated levels (accuracy 93%) and in 19 of 25 operated sides (accuracy 76%). For CT/MRI, sensitivities of 60% and 73% and accuracies of 90% and 80% were found per level and side, respectively. In the six patients with seven tumorinvolved neck levels and sides, immuno-PETand 18 F-fluoro-2-deoxy-D-glucose PETgave comparable diagnostic results. Conclusion: In this study, immuno-PET with 89 Zr-cmAb U36 performed at least as good as CT/MRI for detection of HNSCC lymph node metastases.

Immuno-PET is an appealing concept in the detection of tumors and planning of antibody-based therapy. For this purpose, the long-lived positron emitter 89 Zr (half-life, 78.4 h) recently became available. The aim of the present first-in-humans 89 Zr immuno-PET study was to assess safety, biodistribution, radiation dose, and quantification of the 89 Zr-labeled chimeric monoclonal antibody (cmAb) U36 in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the performance of immuno-PET for detecting lymph node metastases was evaluated, as described previously. Methods: Twenty HNSCC patients, scheduled to undergo surgical tumor resection, received 75 MBq of 89 Zr-cmAb U36 (10 mg). Immuno-PET scans were acquired at 1, 24, 72, or 144 h after injection. The biodistribution of the radioimmunoconjugate was evaluated by ex vivo radioactivity measurement in blood and in biopsies from the surgical specimen obtained at 168 h after injection. Uptake levels and residence times in blood, tumors, and organs of interest were derived from quantitative immuno-PET studies, and absorbed doses were calculated using OLINDA/EXM 1.0. The red marrow dose was calculated using the residence time for blood. Results: 89 Zr-cmAb U36 was well tolerated by all subjects. PET quantification of blood-pool activity in the left ventricle of the heart showed a good agreement with sampled blood activity (difference equals 0.2% 6 16.9% [mean 6 SD]) except for heavyweight patients (.100 kg). A good agreement was also found for the assessment of mAb uptake in primary tumors (mean deviation, 28.4% 6 34.5%). The mean absorbed red marrow dose was 0.07 6 0.02 mSv/MBq and 0.09 6 0.01 mSv/MBq in men and women, respectively. The normal organ with the highest absorbed dose was the liver (mean dose, 1.25 6 0.27 mSv/MBq in men and 1.35 6 0.21 mSv/MBq in women), thereafter followed by kidneys, thyroid, lungs, and spleen. The mean effective dose was 0.53 6 0.03 mSv/MBq in men and 0.66 6 0.03 mSv/MBq in women. Measured excretion via the urinary tract was less than 3% during the first 72 h. Conclusion: 89 Zr immuno-PET can be safely used to quantitatively assess biodistribution, uptake, organ residence times, and radiation dose, justifying its further clinical exploitation in the detection of tumors and planning of mAbbased therapy. Monocl onal antibodies (mAbs) have been approved for use as diagnostics and therapeutics in a broad range of medical indications, but especially in oncology (1). Immuno-PET, the tracking and quantification of mAbs with PET in vivo, is an exciting novel option to improve diagnostic imaging and to guide mAb-based therapy and has been described previously (2-6).To enable PET of mAbs, an appropriate positron emitterwith a half-life (t 1/2 ) that is compatible with the time needed to achieve optimal tumor-to-nontumor ratios (typically 2-4 d for intact mAbs)-has to be securely coupled to the targeting molecule. 124 I (t 1/2 , 100.3 h) and 89 Zr (t 1/2 , 78.4 h) are particularly suitable in combination with intact mAbs, becaus...

Our observations indicate that body fat composition in IVF children is disturbed. Follow-up of IVF children to monitor body fat pattern and potentially related health problems from adolescence into adulthood is of great importance.

Our data suggest that bone metabolism markers are good predictors of bone mass in boys and of bone mass increase in both sexes. In early puberty, sex steroids stimulate the pubertal growth spurt in conjunction with GH and IGF-1. The fast increase in height gives rise to an increase in bone turnover and bone mineral apposition. It is known that at the end of puberty high levels of oestradiol inhibit chondrocyte proliferation. This leads to a decline in height velocity and bone turnover. Bone mass still increases under the influence of sex steroids and IGF-1. The data in our study confirm previous reports that markers of bone turnover relate positively to height velocity.

The mat-forming cyanobacterium Phormidium murrayi West and West isolated from a meltwater pond on the McMurdo Ice Shelf was grown in unialgal batch cultures to evaluate the temperature dependence of ultraviolet radiation (UVR) effects on pigment composition, growth rate, and photosynthetic characteristics. Chlorophyll a concentrations per unit biomass were generally reduced in cells grown under UVR (low UV-A plus UV-B). In vivo absorbance spectra showed that the carotenoid/chlorophyll a ratio increased as a function of photosynthetically available radiation (PAR) and UVR exposure and varied inversely with temperature. Ultraviolet inhibition of growth (percentage reduction of max at each temperature) increased linearly with decreasing temperature, consistent with the hypothesis that net inhibition represents the balance between temperature-independent photochemical damage and temperaturedependent biosynthetic repair. There was no significant effect of UVR on photosynthesis over the first hour of exposure, but significant UV inhibition was observed after 5 days. Unlike growth, however, there was no apparent effect of temperature on the magnitude of UV inhibition of photosynthesis. These results imply that assays of UVR effects on photosynthesis are not an accurate guide to growth responses and that low ambient temperatures can have a major influence on the UV sensitivity of polar organisms. In a set of assays at 20Њ C (preacclimation under 300 mol photons·m Ϫ2 ·s Ϫ1 and 20Њ C), growth was strongly depressed by UVR over the first day of exposure but then gradually increased over the subsequent 4 days, approaching the growth rates in the minus UVR control. This evidence of acquired tolerance indicates that the damaging effects of UVR will be most severe in environments where there is a mismatch between the timescale of change in exposure and the timescale of UV acclimation.

This study aimed to assess the relative importance of several determinants of bone mineral density (BMD) and to examine to what extent these potential determinants influence total hip BMD through body composition. The study population consisted of 522 participants (264 women and 258 men) of the Longitudinal Aging Study Amsterdam (LASA), aged 65 years and over, and living in Amsterdam and its vicinity. BMD of the total hip was measured using dual-energy X-ray absorptiometry (DXA). Potential determinants of BMD were age, weight change since age 25 years, lifestyle factors, chronic diseases, medication use, and hormonal factors. Potential mediators between the possible determinants and BMD were two measures of body composition: fat mass (FM) and appendicular muscle mass (AMM). Multiple regression analyses including all potential determinants in one model without body composition identified age, weight change, walking activity, and sex hormone-binding globulin (SHBG) as independent determinants for total hip BMD in women. In men, current smoking, participation in sports, and parathyroid hormone (PTH) concentration were independently associated with total hip BMD. When total hip BMD was regressed on the potential determinants and each measure of body composition, it appeared that FM, and to a lesser extent, muscle mass (MM), were independently related to BMD. In women, adjustment for FM reduced the strength of the associations of weight change, walking activity, and SHBG with total hip BMD. Adjustments for MM did not influence the associations between the determinants and BMD. In men, neither FM nor MM appeared to play a mediating role between the determinants and BMD. It can be concluded that (1) FM and MM are strong independent determinants of total hip BMD and that (2) FM possibly plays a mediating role in the association of weight change, walking activity, and SHBG with total hip BMD in women.

SUMMARY Twenty-three patients with different degrees of renal insufficiency were studied after equilibration on two levels of salt intake. Blood pressure was found to increase after increased salt intake. This blood pressure increase, when related to sodium excretion increase (salt sensttirity index), tended to be larger in patients with a greater loss of kidney function. In fact, the salt sensitivity of blood pressure rose exponentially with tbe decline of the kidney function, which resulted In a linear negative relationship between tbe log of salt sensitivity index and creatinine clearance (r -0.89, p < 0.0001). After increased salt intake, plasma renin activity (PRA) decreased, whereas body-fluid volumes Increased. Concotnitantly, the products of log PRA and extracellular-fluid volume or blood volume decreased (p < 0.005). Weak interrelations were found between increases of body fluid volumes and blood pressure (r -0.49, p < 0.05). When the patients were divided into two groups according to creatinine clearance, Group 2 (creatinlne clearance < 22 ml/mln, n • 13) showed a significantly greater increase of blood pressure for any given expansion of extracellular fluid volume than Group 1 (creatinine clearance > 32 ml/mln, n -9). Moreover, for any given increase in sodium excretion blood volume increased more in Group 2 than in Group 1 (p < 0.03), whereas the increase of extracellular fluid volume was similar in the two groups. Consequently, after increase of salt intake the plasma volume/interstitial fluid volume ratio (PV/IF) tended to decrease in Group 1 and to increase in Group 2. This difference In PV/IF ratio behavior was significant (p < 0.01). A significant interrelation was also found between the salt sensitivity index and change of PV/IF ratio (r =• 0.60, p < 0.01). It is concluded that, with decrease in functioning renal mass, the salt sensitivity of tbe blood pressure increases. This increase in salt sensitivity is accompanied by an increased intra/extravascular-fluld volume ratio after salt loading, which suggests a change of tissue-capillary filtration forces in patients with renal insufficiency.

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