Concluding remarks. The Window of Opportunity: Pre-Pregnancy to 24 Months of Age.

This symposium focused on the window of opportunity for nutritional interventions to prevent chronic disease. Following a recommendation by the UN Standing Committee on Nutrition, 2006, the window of opportunity was defined as the period from conception to 2 years after birth. We discussed what is known and what needs to be known about (a) growth during this window, (b) critical periods of development, (c) the effects of nutrition, and (d) possible interventions to improve nutrition.

Noncontinuous froude number scaling for the closure depth of a cylindrical cavity.

A long, smooth cylinder is dragged through a water surface to create a cavity with an initially cylindrical shape. This surface void then collapses due to the hydrostatic pressure, leading to a rapid and axisymmetric pinch-off in a single point. Surprisingly, the depth at which this pinch-off takes place does not follow the expected Froude(1/3) power law.

An 86Y-labeled mirror-image oligonucleotide: influence of Y-DOTA isomers on the biodistribution in rats.

A mirror-image oligonucleotide (L-RNA) was radiolabeled with the positron emitting radionuclide (86)Y (t(1/2) = 14.7 h) via the bifunctional chelator approach. DOTA-modification of the L-RNA (sequence: 5'-aminohexyl UGA CUG ACU GAC-3'; MW 3975) was performed using (S)-p-SCN-Bn-DOTA.

Yttrium-86-labelled human serum albumin microspheres: relation of surface structure with in vivo stability.

Introduction: Radiolabelled particles are an attractive tool in the therapy of malignancies of the liver. We consider particles manufactured from denatured human serum albumin (HSA) as useful carriers of therapeutic radionuclides. Covalent attachment of suitable chelators onto the surface of the spheres promises an easy access to radiolabelled HSA microspheres.

Synthesis, Copper(II) Complexation, (64)Cu-Labeling, and Bioconjugation of a New Bis(2-pyridylmethyl) Derivative of 1,4,7-Triazacyclononane.

A new ligand derivative of 1,4,7-triazacyclononane (TACN), 2-[4,7-bis(2-pyridylmethyl)-1,4,7-triazacyclononan-1-yl]acetic acid ( 6), has been synthesized and its complexation behavior toward Cu2+ ions investigated. The ligand 6 has been characterized by spectroscopic methods, and a molecular structure of a corresponding Cu(II) complex has been elucidated by single-crystal X-ray analysis. The suitability of 6 for conjugation to peptide substrates has been shown by amide coupling of 6 to the stabilized derivative of bombesin (BN), beta Ala-beta Ala-[Cha13, Nle14]BN(7-14), to give the conjugate 8.

Undernutrition and growth restriction in pregnancy.

Newborn size is the result of intrauterine growth. Premature, low birthweight of <2,500 g, small for gestational age (SGA, <10th percentile), or intrauterine growth-restricted (IUGR) newborns may have similar weights. Serial fetal biometry (ultrasound), required for the diagnosis, timing and severity of intrauterine growth restriction in the individual infant, is still not common in epidemiological studies.

L-type amino acid transporters LAT1 and LAT4 in cancer: uptake of 3-O-methyl-6-18F-fluoro-L-dopa in human adenocarcinoma and squamous cell carcinoma in vitro and in vivo.

Unlabelled: Expression of system L amino acid transporters (LAT) is strongly increased in many types of tumor cells. The purpose of this study was to demonstrate that (18)F-labeled amino acids, for example, 3-O-methyl-6-(18)F-fluoro-L-dopa ((18)F-OMFD), that accumulate in tumors via LAT represent an important class of imaging agents for visualization of tumors in vivo by PET.

Methods: (18)F-OMFD uptake kinetics, transport inhibition, and system L messenger RNA expression were studied in vitro in human adenocarcinoma (HT-29), squamous cell carcinoma (FaDu), macrophages (THP-1), and primary aortic endothelial cells (HAEC) and in vivo in the corresponding mouse tumor xenograft models.

Modified "4 + 1" mixed ligand technetium-labeled fatty acids for myocardial imaging: evaluation of myocardial uptake and biodistribution.

Our group previously synthesized 99m Tc-labeled fatty acids suitable for myocardial metabolism and flow imaging. In this set of experiments, 29 new analogues were synthesized according to the "4 + 1" mixed ligand approach with some specific differences. Conventional "4 + 1" 99m Tc-fatty acids are built in the sequence: Tc-chelate, alkyl chain, and carboxylic group.

Very stable 188Re-S4 chelates for labelling biomolecules: preparation with highly concentrated perrhenate eluates.

Aim: The preparation and stability of a new (188)Re-S(4)-complex [S(4) = (1-aza-18-crown-6)(O)C-C(SH)-C(SH)-C(O)NH-(CH(2))(3)-NH-(CH(2))(3)-NHC(O)-C(SH)-C(SH)-C(O)(1-aza-18-crown-6] was studied at therapeutic relevant radioactive concentrations. The results were compared with (188)Re-MAG(3) (MAG(3): mercaptoacetyltriglycine) and (188)Re-DMSA preparations (DMSA: dimercaptosuccinic acid) performed with the same highly concentrated [(188)Re]perrhenate solution (12-15 GBq/ml).

Methods: The (188)Re complexes were prepared by direct reduction of perrhenate ((188)Re-S(4)-complex) as well as via the (188)Re-EDTA precursor complex ((188)Re-MAG(3), (188)Re-DMSA).

[Multiple roles and quality of life of mothers two years after the birth of the first child].

Topic: We studied those characteristics of mothers that are related to occupational activity two years after the birth of the first child. Differences in the health-related quality of life between working mothers and mothers who are not working were also analysed, taking other parameters into account, in particular household income.

Methodology: 311 mothers with a first child were given a questionnaire on the quality of life based on WHOQOL-BREF, on depression (also surveyed one year before for 139 mothers), on their work situation, socio-demography and other possible confounders.

Role of air in granular jet formation.

A steel ball impacting on a bed of very loose, fine sand results in a surprisingly vigorous jet which shoots up from the surface of the sand [D. Lohse, Phys. Rev.

Myocardial uptake and biodistribution of newly designed technetium-labelled fatty acid analogues.

Purpose: In an effort to develop 99mTc-labelled fatty acids (FAs) for myocardial metabolism and flow imaging, several Tc analogues according to the '3+1' and the '4+1' mixed-ligand approach were synthesized and myocardial extraction was evaluated in non-working isolated guinea pig hearts. An example of biodistribution patterns in guinea pigs was determined by using one FA analogue.

Methods: The coordination moieties contain a +5, respectively +3, oxidation state metal core attached to the end position of a FA chain.

Fibronectin is elevated in the cerebrospinal fluid of patients suffering from bacterial meningitis and enhances inflammation caused by bacterial products in primary mouse microglial cell cultures.

Toll-like receptors (TLR) play a key role in the recognition of pathogenic organisms. Fibronectin, an extracellular matrix protein, is considered a potent stimulator of the innate immune system through TLR4. In bacterial meningitis, several extracellular matrix proteins and bacterial compounds are elevated in the CSF.

[Perinatal risk factors for long-term health. Results of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS)].

KIGGS is a health survey on 17,641 children and adolescents in 167 communities representative for Germany, conducted between May 2003 and May 2006. Of the perinatal indicators, only a small proportion of data important for long-term outcomes was available for statistical analysis, and is presented here. In the past 20 years the mean weight gain during pregnancy has increased significantly by 2 kg, the mean birth weight has increased significantly by an average of 50 g, there has been no significant time trend for smoking and alcohol consumption in pregnancy.

[Distribution, duration and temporal trend of breastfeeding in Germany. Results of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS)].

Breast milk is the most natural and best type of nutrition for almost all infants. Moreover, breastfeeding is associated with health benefits for mother and child: breast milk supports the development of the infant and protects it against diseases; the health benefits for the mothers also extend beyond the period after birth. Therefore, the WHO recommends exclusive breastfeeding for at least six months.

Effect of increase of radiation dose on local control relates to pre-treatment FDG uptake in FaDu tumours in nude mice.

Objectives: To investigate whether heterogeneity in [(18)F]2-fluoro-2-deoxy-d-glucose (FDG) uptake in a single tumour line, i.e. in tumours with identical genetic background, relates to radiation response.

Synthesis and radiopharmacological characterization of [11C]AL-438 as a nonsteroidal ligand for imaging brain glucocorticoid receptors.

The radiosynthesis and the radiopharmacological characterization of [(11)C]AL-438 as a nonsteroidal ligand for the glucocorticoid receptor (GR) is described. Radiolabeling of the corresponding desmethyl precursor 10 with [(11)C]MeI gave [(11)C]AL-438 in decay-corrected radiochemical yields of 30+/-4% (based upon [(11)C]CO(2)) within 35 min at a specific radioactivity of 10-15 GBq/micromol at the end-of-synthesis. The radiopharmacological evaluation of [(11)C]AL-438 involved biodistribution and small animal PET imaging in rats, and autoradiography studies using rat brain sections.

SHOP: scaffold HOPping by GRID-based similarity searches.

A new GRID-based method for scaffold hopping (SHOP) is presented. In a fully automatic manner, scaffolds were identified in a database based on three types of 3D-descriptors. SHOP's ability to recover scaffolds was assessed and validated by searching a database spiked with fragments of known ligands of three different protein targets relevant for drug discovery using a rational approach based on statistical experimental design.

Synthesis and radiopharmacological characterization of 2beta-carbo-2'-[18F]fluoroethoxy-3beta-(4-bromo-phenyl)tropane ([18F]MCL-322) as a PET radiotracer for imaging the dopamine transporter (DAT).

The fluoroalkyl-containing tropane derivative 2beta-carbo-2'-fluoroethoxy-3beta-(4-bromo-phenyl)tropane (MCL-322) is a highly potent and moderately selective ligand for the dopamine transporter (DAT). The compound was labeled with the short-lived positron emitter (18)F in a single step by nucleophilic displacement of the corresponding tosylate precursor MCL-323 with no-carrier-added [(18)F]fluoride. The positron emission tomography (PET) radiotracer 2beta-carbo-2'-[(18)F]fluoroethoxy-3beta-(4-bromo-phenyl)tropane [(18)F]MCL-322 was obtained in decay-corrected radiochemical yields of 30-40% at a specific radioactivity of 1.

Radiolabeling of multimeric neurotensin(8-13) analogs with the short-lived positron emitter fluorine-18.

Three methods for (18)F-labeling of dimeric and tetrameric neurotensin(8-13) derivatives were evaluated with respect to the labeling yield and the required peptide amounts. Labeling using N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB) gave low radiochemical yield for the dimeric peptides. Coupling of the tetramer with [(18)F]SFB was not successful.

Experimental hypoxia is a potent stimulus for radiotracer uptake in vitro: comparison of different tumor cells and primary endothelial cells.

Hypoxia causes upregulation of vascular endothelial growth factor (VEGF) which is a key regulator in tumor angiogenesis and essential for the proliferation of endothelial cells. Endothelial cells have been described to accumulate radiotracers like (18)F-FDG. However, the contribution of radiotracer uptake by endothelial cells to uptake measured in tumors by positron emission tomography (PET) is still unclear.

Synthesis and biological evaluation of a new type of 99mtechnetium-labeled Fatty Acid for myocardial metabolism imaging.

Technetium-labeled fatty acids intended for myocardial metabolism imaging and the respective rhenium model complexes were synthesized according to the "4 + 1" mixed-ligand approach and investigated in vitro and in vivo. The non-radioactive rhenium model complexes were characterized by NMR, IR, and EA, and the geometrical impact of the chelate unit on the integrity of the fatty acid head structure was determined by single-crystal X-ray analyses. To estimate the diagnostic value of the 99mTc-labeled fatty acids, the compounds were investigated in experiments in vitro and in biodistribution studies using male Wistar rats.

Preparation and biological characterization of isomeric 188Re(V) oxocomplexes with tetradentate S4 ligands derived from meso-dimercaptosuccinic acid for labeling of biomolecules.

A new type of tetradentate S4 ligand has been synthesized by bridging two molecules of meso-2,3-dimercaptosuccinic acid for stable binding and easy conjugation of rhenium-188 to tumor targeting structures. The stereoisomeric tetrathiolato S4 ligands form very robust anionic five-coordinated oxorhenium(V) and oxotechnetium(V) complexes. Two routes for the preparation of the (188)Re(V) oxocomplexes with (iBu)2N(O)C-C(SH)C(SH)C(O)NH(CH2)3NH(CH2)3NHC(O)C(SH)C(SH)C(O)N(iBu)2 (ligand 1) and its hydrophilic crown ether derivative (ligand 2) were tested and optimized.

Neurotensin receptors in adeno- and squamous cell carcinoma.

Background: Peptide receptors seem to be good markers for receptor targeting because of their overexpression in human cancer. Understanding the role of receptors and their cognate ligands, they are currently used for both diagnosis and therapy. Candidates playing a key role in tumor biology are the neurotensin receptors (NTR).