Novel Bispecific PSMA/GRPr Targeting Radioligands with Optimized Pharmacokinetics for Improved PET Imaging of Prostate Cancer.

A new series of bispecific radioligands (BRLs) targeting prostate-specific membrane antigen (PSMA) and gastrin releasing peptide receptor (GRPr), both expressed on prostate cancer cells, was developed. Their design was based on the bombesin (BN) analogue, H2N-PEG2-[D-Tyr(6),ß-Ala(11),Thi(13),Nle(14)]BN(6-14), which binds to GRPr with high affinity and specificity, and the peptidomimetic urea-based pseudoirreversible inhibitor of PSMA, Glu-ureido-Lys. The two pharmacophores were coupled through copper(I)-catalyzed azide-alkyne cycloaddition to the bis(tetrafluorophenyl) ester of the chelating agent HBED-CC via amino acid linkers made of positively charged His (H) and negatively charged Glu (E): -(HE)n- (n = 0-3). The BRLs were labeled with (68)Ga, and their preliminary pharmacological properties were evaluated in vitro (competitive and time kinetic binding assays) on prostate cancer (PC-3, LNCaP) and rat pancreatic (AR42J) cell lines and in vivo by biodistribution and small animal PET imaging studies in both normal and tumor-bearing mice. The IC50/Ki values determined for all BRLs essentially matched those of the respective monomers. The maximal cellular uptake of the BLRs was observed between 20 and 30 min. The BRLs showed a synergistic ability in vivo by targeting both PSMA (LNCaP) and GRPr (PC-3) positive tumors, whereas the charged -(HE)n- (n = 1-3) linkers significantly reduced the kidney and spleen uptake. The bispecific (PSMA and GRPr) targeting ability and optimized pharmacokinetics of the compounds developed in this study could lead to their future application in clinical practice as more sensitive radiotracers for noninvasive imaging of prostate cancer (PCa) by PET/CT and PET/MRI.

Temporal and spatial distribution of ST-elevation myocardial infarction admissions in a countrywide registry.

BACKGROUND: Current guidelines propose different reperfusion strategies for ST-elevation myocardial infarction (STEMI) depending on the time delay from pain onset, the availability of a catheterization laboratory and the patient's characteristics. In order to implement national strategies to improve reperfusion rates the existing situation must be first analysed. The aim of this report is to provide a description of where and when STEMI patients present in a countrywide registry. METHODS: The Hellenic Infarction Observation Study (HELIOS) was a countrywide registry that enrolled 1096 patients with STEMI from 31 hospitals with a proportional representation of all types of hospitals from all geographical areas. We recorded the proportion of patients that fits within each category of treatment algorithms. RESULTS: The following percentages of the total STEMI population were recorded: a) admitted in invasive hospitals within 12 h 28.7% (with 26% of those not reperfused) and after 12 h 5.9% and b) admitted in non-invasive hospitals within 3 h 34.9% (with 30% of those not reperfused), 3-12 h 19.3% and after 12 h 11%. CONCLUSIONS: A large proportion of STEMI patients are admitted either in an invasive hospital within 12 h or in a non-invasive one within 3 h from pain onset and therefore can be treated locally according to the guidelines. A relatively small percentage of patients are late presenters in non-invasive centres and are candidates for immediate transfer for primary PCI. These data could be useful in planning reperfusion strategies at countrywide level since not all patients may require immediate transfer for primary PCI.

Fatty acids, sterols, phenols and antioxidant activity of Phoenix theophrasti fruits growing in Crete, Greece.

In the present study we report the chemical composition of the Cretan Phoenix theophrasti Gr. fruits, in comparison with dates, from its close relative Phoenix dactylifera L. for their nutritional value and their potential exploitation as a source of bioactive components such as phytosterols, lipids and polyphenols. The non polar dichloromethane (CH2Cl2) extract of the fruits was analysed by several techniques (TLC, CC, GC and GC-MS) and was found to consist mainly from fatty acids, hydrocarbons and phytosterols. Palmitic acid was the most abundant fatty acid, 12.49% of total saponifiables, while beta-sitosterol was the most prevalent phytosterol, 29.46% of total unsaponifiable lipid fraction. The polar methanolic extract was examined for its total phenolic content, by the Folin-Ciocalteu assay, as well as for its antioxidant activity through DPPH assay, in comparison with previous studies on the fruits of several Phoenix dactylifera varieties. This fraction was found to possess strong antioxidant activity despite its lower content of phenolic compounds in comparison with previously studied Phoenix dactylifera specimens.