This report describes the design and synthesis of a series of a V b 3 integrin-directed monomeric, dimeric and tetrameric cyclo [Arg-Gly-Asp-D-Phe-Lys] dendrimers using "click chemistry". It was found that the unprotected N-e-azido derivative of cyclo[Arg-Gly-Asp-D-Phe-Lys] underwent a highly chemoselective conjugation to amino acid-based dendrimers bearing terminal alkynes using a microwave-assisted Cu(I)-catalyzed 1,3-dipolar cycloaddition. The a V b 3 binding characteristics of the dendrimers were determined in vitro and their in vivo a V b 3 targeting properties were assessed in nude mice with subcutaneously growing human SK-RC-52 tumors. The multivalent RGD-dendrimers were found to have enhanced affinity toward the a V b 3 integrin receptor as compared to the monomeric derivative as determined in an in vitro binding assay. In case of the DOTA-conjugated 111 In-labeled RGD-dendrimers, it was found that the radiolabeled multimeric dendrimers showed specifically enhanced uptake in a V b 3 integrin expressing tumors in vivo. These studies showed that the tetrameric RGD-dendrimer had better tumor targeting properties than its dimeric and monomeric congeners.

PurposeDocetaxel is an important chemotherapeutic agent used for the treatment of several cancer types. As radiolabelled anticancer agents provide a potential means for personalized treatment planning, docetaxel was labelled with the positron emitter 11C. Non-invasive measurements of [11C]docetaxel uptake in organs and tumours may provide additional information on pharmacokinetics and pharmacodynamics of the drug docetaxel. The purpose of the present study was to determine the biodistribution and radiation absorbed dose of [11C]docetaxel in humans.MethodsBiodistribution of [11C]docetaxel was measured in seven patients (five men and two women) with solid tumours using PET/CT. Venous blood samples were collected to measure activity in blood and plasma. Regions of interest (ROI) for various source organs were defined on PET (high [11C]docetaxel uptake) or CT (low [11C]docetaxel uptake). ROI data were used to generate time-activity curves and to calculate percentage injected dose and residence times. Radiation absorbed doses were calculated according to the MIRD method using OLINDA/EXM 1.0 software.ResultsGall bladder and liver demonstrated high [11C]docetaxel uptake, whilst uptake in brain and normal lung was low. The percentage injected dose at 1 h in the liver was 47 ± 9%. [11C]docetaxel was rapidly cleared from plasma and no radiolabelled metabolites were detected. [11C]docetaxel uptake in tumours was moderate and highly variable between tumours.ConclusionThe effective dose of [11C]docetaxel was 4.7 µSv/MBq. As uptake in normal lung is low, [11C]docetaxel may be a promising tracer for tumours in the thoracic region.

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