An Automated and Putatively Versatile Approach for Labeling Peptides with Fluorine-18 Using the FastlabTM Synthesizer; Exemplified with Glu-the CO-Lys Pharmacophore

Background: Noninvasive molecular imaging using peptides and biomolecules labelled with positron emitters has become important for detection of cancer and other diseases with PET (positron emission tomography). The positron emitting radionuclide fluorine-18 is widely available in high yield from cyclotrons and has favorable decay (t1/2 109.7 min) and imaging properties. 18F-Labelling of biomolecules and peptides for use as radiotracers is customarily achieved in a two-step approach, which can be challenging to automate. 6-[18F]Fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester ([18F]F-Py-TFP) is a versatile 18F-prosthetic group for this purpose, which can be rapidly be produced in an one-step approach on solid support. This work details an automated procedure on the cassette-based GE FASTlabTM platform for the labeling of a peptidomimetic, exemplified by the case of using the Glu-CO-Lys motif to produce [18F]DCFPyL, a ligand targeting the prostate specific membrane antigen (PSMA). Results: From fluorine-18 delivery a fully automated two-step radiosynthesis of [18F]DCFPyL was completed in 56 min with an overall end of synthesis yield as high as 37% using SPE purification on the GE FASTlabTM platform. Conclusions: Putatively, this radiolabeling methodology is inherently amenable to automation with a diverse set of synthesis modules, and it should generalize for production of a broad spectrum of biomolecule-based radiotracers for use in PET imaging.

Production of scandium radionuclides for theranostic applications: towards standardization of quality requirements

In the frame of “precision medicine”, the scandium radionuclides have recently received considerable interest, providing personalised adjustment of radiation characteristics to optimize the efficiency of medical care or therapeutic benefit for particular groups of patients. Radionuclides of scandium, namely scandium-43 and scandium-44 (43/44Sc) as positron emitters and scandium-47 (47Sc), beta-radiation emitter, seem to fit ideally into the concept of theranostic pair. This paper aims to review the work on scandium isotopes production, coordination chemistry, radiolabeling, preclinical studies and the very first clinical studies. Finally, standardized procedures for scandium-based radiopharmaceuticals have been proposed as a basis to pave the way for elaboration of the Ph.Eur. monographs for perspective scandium radionuclides.

Infection imaging using [18F]FDG-labelled white blood cell positron emission tomography–computed tomography

Localizing the sites of infection in the body is possible in nuclear medicine using a variety of radiopharmaceuticals that target different components of the infective and inflammatory cascade. Gamma(γ)-emitting agents such as [67Ga]gallium citrate were among the first tracers used, followed by development of positron-emitting tracers like 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). Though these tracers are quite sensitive, they have limited specificity for infection due to their concentration in sites of non-infective inflammation. White blood cells (WBC) labelled with γ or positron emitters have higher accuracy for differentiating the infective processes from the non-infective conditions that may show positivity with tracers such as 18F-FDG. We present a pictorial review of potential clinical applications of PET/CT using 18F-FDG labelled WBC.

The Metamorphosis of Radionuclide Production and Development at Paul Scherrer Institute

Radionuclide production and development has a long history at the Paul Scherrer Institute (PSI) and dates back to the founding times of its forerunner institutions: the Federal Institute for Reactor Research and the Swiss Institute for Nuclear Research. The facilities used for this purpose have evolved substantially over the last five decades. Many radiometals in use today, as radiopharmaceuticals, are for the diagnosis and treatment of disease, with the most popular means of detection being Positron Emission Tomography. These positron emitters are easily produced at low proton energies using medical cyclotrons, however, developments at these facilities are lacking. Currently, the fixed 72 MeV proton beam at PSI is degraded at IP2 irradiation station to provide the desired energy to irradiate targets to produce the likes of 44Sc, 43Sc and 64Cu as a proof of principle, which are of great interest to the nuclear medicine community. This development work can then be implemented at facilities containing medical cyclotrons. A history of the development of radionuclides at PSI, along with current development and projects with partner institutions, is described.

An Update on Extemporaneous Preparation of Radiopharmaceuticals Using Freeze-Dried Cold Kits

Abstract:: The field of nuclear medicine is rapidly evolving due to the high demand of radiopharmaceuticals for diagnostic and therapeutic applications. The availability of a vast array of radioisotopes, improvement in radiolabeling strategies, and advancements in detection systems have also contributed to the progress in this field. Radiopharmaceuticals are mainly classified based on their application as diagnostic or therapeutic radiopharmaceuticals. These are available either as ready to use preparations or prepared at hospital radiopharmacy either using automated synthesis modules or by using freeze-dried cold kit formulations. Availability of freeze-dried cold kits for preparation of varied radiopharmaceuticals for targeting various organs and tissues played an essential role in the extensive use of 99mTc radiopharmaceuticals for diagnostic imaging by single-photon emission computed tomography (SPECT) imaging. Cold kits are especially suitable for the preparation of radiopharmaceuticals labeled with isotopes like 177Lu with relatively long half-life or radionuclides produced by radioisotope generators. A simplified procedure for the preparation of positron emission tomography (PET) radiopharmaceuticals is also desired to achieve images with higher resolution and sensitivity offered by PET. Robust kit formulations will simplify the preparation of PET radiopharmaceuticals and will contribute to extensive applications of positron emitters such as 68Ga. Several therapeutic radiopharmaceuticals are also being made using cold kits of the ligands. This review provides an update on diagnostic and therapeutic radiopharmaceuticals prepared using cold kits.

Evaluation of image quality with four positron emitters and three preclinical PET/CT systems

Background We investigated the image quality of 11C, 68Ga, 18F and 89Zr, which have different positron fractions, physical half-lifes and positron ranges. Three small animal positron emission tomography/computed tomography (PET/CT) systems were used in the evaluation, including the Siemens Inveon, RAYCAN X5 and Molecubes β-cube. The evaluation was performed on a single scanner level using the national electrical manufacturers association (NEMA) image quality phantom and analysis protocol. Acquisitions were performed with the standard NEMA protocol for 18F and using a radionuclide-specific acquisition time for 11C, 68Ga and 89Zr. Images were assessed using percent recovery coefficient (%RC), percentage standard deviation (%STD), image uniformity (%SD), spill-over ratio (SOR) and evaluation of image quantification. Results 68Ga had the lowest %RC (< 62%) across all systems. 18F had the highest maximum %RC (> 85%) and lowest %STD for the 5 mm rod across all systems. For 11C and 89Zr, the maximum %RC was close (> 76%) to the %RC with 18F. A larger SOR were measured in water with 11C and 68Ga compared to 18F on all systems. SOR in air reflected image reconstruction and data correction performance. Large variation in image quantification was observed, with maximal errors of 22.73% (89Zr, Inveon), 17.54% (89Zr, RAYCAN) and − 14.87% (68Ga, Molecubes). Conclusions The systems performed most optimal in terms of NEMA image quality parameters when using 18F, where 11C and 89Zr performed slightly worse than 18F. The performance was least optimal when using 68Ga, due to large positron range. The large quantification differences prompt optimization not only by terms of image quality but also quantification. Further investigation should be performed to find an appropriate calibration and harmonization protocol and the evaluation should be conducted on a multi-scanner and multi-center level.