Pharmacodynamics of [D-Ser (t-Bu)6,Des-Gly10]GnRH ethylamide (Buserelin) in 6 normal volunteers. Its usefulness to monitor treatment of central precocious puberty

The disappearance rate of [D-Ser(t-bu)6,des-Gly10]GnRH ethylamide (Buserelin, HOE 766) was studied in plasma and urine after intranasal (300 micrograms) or sc (10 micrograms/kg) administration. A radioimmunoassay for HOE 766 was developed using 125I[D-Trp6,Des-Gly10]GnRH ethylamide as tracer and an antiserum raised against HOE 766. Cross-reaction with native GnRH was only 1.7%. Sensitivity was 1 pg/tube. In 6 male adolescents, the mean plasma HOE 766 concentration (+/- SEM) was 0.46 +/- 0.08, 0.50 +/- 0.10, 0.28 +/- 0.04, 0.24 +/- 0.04, 0.13 +/- 0.03, and 0.08 +/- 0.02 micrograms/l 30, 60, 90, 120 and 180 min after the intranasal administration, respectively. Concomitant urinary excretion of HOE 766-like material was 9.43 +/- 1.96 micrograms/4 h. There was a good correlation between integrated plasma levels and urinary excretion (r = 0.92). In the same 6 volunteers, the plasma HOE 766 levels were 21.2 +/- 3.0, 25.9 +/- 0.8, 21.2 +/- 0.9, 17.1 +/- 0.7, 12.8 +/- 1.1, 8.9 +/- 0.4, and 5.9 +/- 0.8 micrograms/l 20, 40, 60, 90, 120, 180 and 240 min after sc injection, respectively. The mean urinary excretion was 543 +/- 61 micrograms/4 h. In two girls with precocious puberty treated during 12 to 15 months with intranasal administration of HOE 766, urinary excretion of HOE 766-like material was shown to correlate well with the degree of inhibition of plasma 17 beta-E2 and of plasma LH and FSH responses to a GnRH challenge. Thus, monitoring of HOE 766 in urine appears to be helpful for evaluating of intranasal therapy with a GnRH analog in precocious puberty.     

Kinetics and 28-day test–retest repeatability and reproducibility of [11C]UCB-J PET brain imaging

[¹¹C]UCB-J is a novel radioligand that binds to synaptic vesicle glycoprotein 2A (SV2A). The main objective of this study was to determine the 28-day test–retest repeatability (TRT) of quantitative [¹¹C]UCB-J brain positron emission tomography (PET) imaging in Alzheimer’s disease (AD) patients and healthy controls (HCs). Nine HCs and eight AD patients underwent two 60 min dynamic [¹¹C]UCB-J PET scans with arterial sampling with an interval of 28 days. The optimal tracer kinetic model was assessed using the Akaike criteria (AIC). Micro-/macro-parameters such as tracer delivery (K₁) and volume of distribution (V_T) were estimated using the optimal model. Data were also analysed for simplified reference tissue model (SRTM) with centrum semi-ovale (white matter) as reference region. Based on AIC, both 1T2k_V_B and 2T4k_V_B described the [¹¹C]UCB-J kinetics equally well. Analysis showed that whole-brain grey matter TRT for V_T, DVR and SRTM BP_ND were –2.2% ± 8.5, 0.4% ± 12.0 and –8.0% ± 10.2, averaged over all subjects. [¹¹C]UCB-J kinetics can be well described by a 1T2k_V_B model, and a 60 min scan duration was sufficient to obtain reliable estimates for both plasma input and reference tissue models. TRT for V_T, DVR and BP_ND was <15% (1SD) averaged over all subjects and indicates adequate quantitative repeatability of [¹¹C]UCB-J PET.     

Therapy-Induced Changes in CXCR4 Expression in Tumor Xenografts Can Be Monitored Noninvasively with N-[11C]Methyl-AMD3465 PET

Molecular Imaging and Biology - Chemokine CXCL12 and its receptor CXCR4 are constitutively overexpressed in human cancers. The CXCL12-CXCR4 signaling axis plays an important role in tumor...     

Growth and pubertal development of young female gymnasts and swimmers: a correlation with parental data

Whereas intensive and regular physical training is known to alter female reproductive function, its potential role in growth is still controversial. At the beginning of a longitudinal growth study of young elite female gymnasts (n = 34, 15-25 h/wk training) and moderately trained swimmers (n = 19, 5-15 h/wk), patterns of recalled parental growth and pubertal maturation were compared with those of parents of 25 sedentary school girls. These data were also correlated to the height, weight, pubertal development as well as adult height prognosis of their daughters. Bone age was estimated using the methods of Greulich-Pyle and Tanner (RUS score) and adult height prognosis using the methods of Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT), and Tanner et al. (TW2). Parents of gymnasts were significantly lighter (fathers: P = 0.027; mothers: P = 0.038) and shorter (fathers: P = 0.034; mothers: P less than 0.001) than those of swimmers and controls. Consequently, target heights of gymnasts were also significantly shorter (P less than 0.001). Recalled menarche occurred significantly later (P = 0.030) in mothers of gymnasts who, in turn, grow much alike their mothers. At the first visit, the gymnasts were shorter and lighter for age than swimmers and controls. Their bone age (11.0 +/- 1.3 years, mean +/- SD) was retarded (P less than 0.001) when compared with chronological age (12.6 +/- 1.2 years). Adult height prognosis was lower for gymnasts than for other girls (BP: P less than 0.001; RWT: P = 0.023, TW2: P less than 0.001), but adequate for target height range.(ABSTRACT TRUNCATED AT 250 WORDS)