Journal of Labelled Compounds and Radiopharmaceuticals

In the interest of developing efficient methods for tritium labelling peptides, we here demonstrate the successful labelling of PACAP-38 (pituitary adenylate cyclase-activating polypeptide), a 38-mer peptide, using a synthetic diiodinated PACAP-38 precursor. In this example, we employ standard hydrogenation chemistry with the use of a heterogeneous palladium catalyst and carrier-free tritium gas on a tritium manifold system.

The positron emitting radionuclide ⁶³Zn was produced from the irradiation of copper targets with protons. Short purification times were achieved by selective elution of zinc ions from cationic resins, and the final product was obtained in high chemical and radiochemical purities.

In an attempt to develop RGD-based radiopharmaceutical, a novel GluDTPA-cyclo(RGDfK) possessing eight coordination sites was synthesized and radiolabeled with ¹⁷⁷Lu as a model radionuclide. The ¹⁷⁷Lu-labeled GluDTPA-cyclo(RGDfK) was formulated with a high yield (>98%) and sustained its radiochemical purity. The radiolabeled complex showed its proper biological affinity as a targeting agent for non-invasive imaging and detection of integrin α_νβ₃-positive tumors.

Microfluidic reactors enable higher radiochemical yields for labeling bifunctional chelates and a protein conjugate with technetium-99m relative to similarly formulated conventional methods.

We report a stereospecific route for the radiofluorination of (2S,4R)-N-tert-butoxycarbonyl-4-(p-toluenesulfonyloxy)proline methyl ester to produce diastereomerically pure cis-4-[¹⁸F]fluoro-l-proline. This work illustrates the effect of temperature on stereospecificity of nucleophilic radiofluorination and proves it to be a determining factor in the production of diastereomerically pure products. Two hydrolysis routes are also discussed for the deprotection of the fluorinated intermediate, providing a critical analysis on the choice of acid or acid/base hydrolysis for production of diastereomerically pure cis-[¹⁸F]4-fluoro-l-proline.

A gramme-scale catalytic synthesis of the deuterated silanes SiEt₃D, SiMe₂PhD and SiPh₂D₂ is reported, utilizing D₂ (0.5 bar) as the hydrogen isotope source and low catalyst loadings (0.01 mol%). The catalytic activity that rhodium complex 1 exhibits also toward hydrosilylation reactions has allowed us to develop a simple and proficient one-flask, two-step procedure for the deuterosilylation of various ketones, aldehydes and α,β-unsaturated nitriles.

A rapid procedure was developed for labeling the plant signaling molecule, azelaic acid (1,9-nonandioic acid), and related acids with ¹¹C or ¹⁴C. Labeling was in two steps via reaction of the bromonitrile with ¹¹C or ¹⁴C-cyanide, respectively, followed by alkaline hydrolysis.

A simple and effective method for synthesis of glucose-d-¹³C₆ via two steps is described. Firstly, the α,α-trehalose-¹³C₁₂ can be obtained by fermentation using the methylotrophic yeast Hansenula polymorpha with 99% abundance methanol-¹³C and then be hydrolysed to give glucose-d-¹³C₆ with 98.5% abundance ¹³C.

A method for the preparation of [³H]levetiracetam with a high specific activity of 98 Ci/mmol (3.6 TBq/mmol) is described. The radioligand proved to be highly useful for the labeling of specific levetiracetam binding sites in rat brain membrane preparations.

This article presents the design and preparation of a single-chain variable fragment (scFv) of an antibody comprising an auxiliary polypeptide segment that is rich in tyrosine. This protein shows a higher capacity to bind iodine radionuclide, as compared with the parental scFv. The tyrosine-rich segment of the tailored protein is less hydrophobic (i.e. more solvent exposed) and can thus contribute to a redirection of the label from potentially sensitive scFv tyrosine residues.