Journal of Labelled Compounds and Radiopharmaceuticals

Filer, Crist N.; Trevorrow, Paul

doi: 10.1002/jlcr.3935pmid: 34318528

Lockley, William. J. S.; Trevorrow, Paul

doi: 10.1002/jlcr.3936pmid: 34318501

Cai, Le; He, Shuhua; Zheng, Xiaobei; Li, Jie; Wang, Hong; Liu, Yuxia; Zhang, Lan

doi: 10.1002/jlcr.3937pmid: 34330148

Amplification pretargeting has the potential to increase the tracer's accumulation in the tumor. This study aimed to develop a three‐step amplification pretargeting strategy in nuclear medicine with a polymer conjugated with multiple copies of peptide nuclear acid (PNA). In this study, the tracer 18F‐labeled complementary PNA (18F‐cPNA) was prepared by click‐chemistry with high radiochemical purity (>99%) and great stability in vitro. The PAMMA dendrimer generation 4 (G4) was conjugated with multiple copies of PNAs. The average number of PNA groups in the G4‐PNA conjugate was determined by matrix‐assisted laser desorption ionization‐time of flight mass spectrometry (MALDI‐TOF MS) and the accessibility to the 18F‐cPNA was identified by size‐exclusion high‐performance liquid chromatography (SE‐HPLC). There were approximately 11.7 of 64 carboxyl groups modified with PNAs, of which more than 99% were accessible to 18F‐cPNA. 18F‐cPNA was added to a mixture of CC49‐cPNA and G4‐PNA, and the complex exhibited a single peak on high‐performance liquid chromatography (HPLC) as evidence of complete hybridization between 18F‐cPNA and CC49‐cPNA/G4‐PNA. The LS174T tumor cells were incubated with CC49‐cPNA followed by G4‐PNA as an amplification platform before 18F‐cPNA was added to hybridize with CC49‐cPNA/G4‐PNA. Compared with conventional pretargeting without G4‐PNA, the radioactivity signal was amplified about four times, which demonstrated that the dendrimer–PNA conjugate plays a crucial role in signal amplification.

Fouque, Julien; Rusu, Timofei; Huguet, Samuel; Branquinho, Emilie Da Costa; Blondeel‐Gomes, Sandy; Rezaï, Keyvan; Madar, Olivier

doi: 10.1002/jlcr.3938pmid: 34355420

Radiolabelling with short half‐lives radionuclides (e.g., fluorine‐18 and carbon‐11) must be as efficient and as fast as possible. Nucleophilic radiofluorinations and radiomethylations are conducted in polar aprotic solvents, such as dimethylsulfoxyde (DMSO), N,N‐dimethylformamide (DMF) and N,N‐dimethylacetamide (DMA), at high temperature. Those solvents are classified as toxic according to the ICH guidelines and must be evaluated in drug such as radiopharmaceuticals. Headspace gas chromatography is the standard method for the quantification of residual solvents but is not optimized for a rapid quantification of low vapor pressure solvents such as DMSO, DMF and DMA in radiopharmaceuticals. Direct injection gas chromatography is an interesting option without incubation step but the analysis run‐time remains beyond 10 min long. In consequence, we developed a very simple ultra‐high performance liquid chromatography method coupled with UV detection. Following the EMA requirements, we successfully validated a 3‐min run‐time analysis for quantification of three solvents in short half‐lives radiopharmaceuticals. We currently use this method for the quality control of radiopharmaceuticals produced in our PET center.

Rokka, Johanna; Nordeman, Patric; Roslin, Sara; Eriksson, Jonas

doi: 10.1002/jlcr.3932pmid: 34250640

The Suzuki‐type cross coupling reaction is a palladium‐mediated multistep reaction that has been used to synthesize several 11C‐labeled tracers for PET. However, the impact of the selected organoborane reagent and reaction medium on the radiochemical yield (RCY) has not been thoroughly investigated. To bridge this gap, we studied the synthesis of 1‐[11C]methylnaphthalene using four different organoborane precursors in reactions performed in DMF/water and THF/water. In the synthesis of 1‐[11C]methylnaphthalene, the best radiochemical yields (RCYs), approximately 50%, were obtained with boronic acid and pinacol ester precursors, whereas less than 4% RCY was obtained when performing the reaction with the N‐methylimidodiacetic acid boronic ester (MIDA ester) precursor. 1‐[11C]methylnaphthalene was obtained in higher yields in almost all syntheses performed in THF/water as compared to DMF/water. This observation was in line with previously reported results for [11C]UCB‐J, a tracer for the synaptic vesicle glycoprotein 2A (SV2A) receptor, that also was obtained in higher RCY when synthesized in THF/water. The same trend was observed with [11C]cetrozole, where the RCY was more than doubled in THF/water compared to the previously published synthesis performed in DMF. These results suggest that THF/water could be the preferred reaction medium when producing PET tracers via the Suzuki‐type coupling reaction.