Positronium is abundantly produced within the molecular voids of a patient’s body during positron emission tomography (PET). Its properties dynamically respond to the submolecular architecture of the tissue and the partial pressure of oxygen. Current PET systems record only two annihilation photons and cannot provide information about the positronium lifetime. This study presents the in vivo images of positronium lifetime in a human, for a patient with a glioblastoma brain tumor, by using the dedicated Jagiellonian PET system enabling simultaneous detection of annihilation photons and prompt gamma emitted by a radionuclide. The prompt gamma provides information on the time of positronium formation. The photons from positronium annihilation are used to reconstruct the place and time of its decay. In the presented case study, the determined positron and positronium lifetimes in glioblastoma cells are shorter than those in salivary glands and those in healthy brain tissues, indicating that positronium imaging could be used to diagnose disease in vivo.

The development of diagnostic methods in medicine as well as the progress in the synthesis of biologically active compounds allows the use of selected radioisotopes for the simultaneous diagnosis and treatment of diseases, especially cancerous ones, in patients. This approach is called theranostic. This review article includes chemical and physical characterization of chosen theranostic radioisotopes and their compounds that are or could be useful in nuclear medicine.

The rapid increase in applications of scandium isotopes in nuclear medicine requires new efficient production routes for these radioisotopes. Recently, irradiations of calcium in cyclotrons by α, deuteron, and proton beams have been used. Therefore, effective post-irradiation separation and preconcentration of the radioactive scandium from the calcium matrix are important to obtain the pure final product in a relatively small volume. Nobias resin was used as a sorbent for effective separation of ⁴⁴Sc from calcium targets. Separation was performed at pH 3 using a column containing 10 mg of resin. Scandium was eluted with 100 μL of 2 mol L⁻¹ HCl. Particular attention was paid to the reduction of calcium concentration, presence of metallic impurities, robustness and simple automation. ⁴⁴Sc was separated with 94.9 ± 2.8% yield, with results in the range of 91.7–99.0%. Purity of the eluate was confirmed with ICP-OES determination of metallic impurities and >99% chelation efficiency with DOTATATE, followed by >36 h radiochemical stability of the complex. A wide range of optimal conditions and robustness to target variability and suspended matter facilitates the proposed method in automatic systems for scandium isotope separation and synthesis of scandium-labeled radiopharmaceuticals.

Pathological angiogenesis, resulting from an imbalance between anti- and pro-angiogenic factors, plays a pivotal role in tumor growth, development and metastasis. The inhibition of the angiogenesis process by the VEGF/VEGFR-2/NRP-1 pathway raises interest in the search for such interaction inhibitors for the purpose of the early diagnosis and treatment of angiogenesis-dependent diseases. In this work we designed and tested peptide-based radiocompounds that selectively bind to the neuropilin-1 co-receptor and prevent the formation of the pro-angiogenic VEGF-A₁₆₅/NRP-1 complex. Three biomolecules, A7R and retro-inverso ^DR7A peptides, and the branched peptidomimetic Lys(hArg)-Dab-Pro-Arg (K4R), conjugated with macrocyclic chelator through two linkers’ types, were labeled with theranostic scandium-44 radionuclide, and studied in vitro as potential targeted radiopharmaceuticals. ELISA (enzyme-linked immunosorbent assay) studies showed no negative effect of the introduced biomolecules’ changes and high NRP-1 affinity in the case of A7R- and K4R-radiocompounds and a lack affinity for ^DR7A-radiocompounds. All radiopeptides showed a hydrophilic nature as well as high stability against ligand exchange reactions in cysteine/histidine solutions. Unfortunately, all radiocompounds showed unsatisfactory nano-scale stability in human serum, especially for use as therapeutic radioagents. Further work is ongoing and focused on the search for angiogenesis inhibitors that are more human serum stable.

Positronium, an unstable atom consisting of an electron and a positron, is abundantly produced within the molecular voids of a patient’s body during positron emission tomography (PET) diagnosis. Its properties, such as its average lifetime between formation and annihilation into photons, dynamically respond to the submolecular architecture of the tissue and the partial pressure of oxygen molecules. However, the diagnostic information that positronium may deliver about early molecular alterations remains unavailable in clinics with state-of-the-art PET scanners. This study presents the first in vivo images of positronium lifetime in humans. We developed a dedicated J-PET system with multiphoton detection capability for imaging. The measurements of positronium lifetime were performed on a patient with a glioblastoma tumor in the brain. The patient was injected intratumorally with the ⁶⁸ Ga radionuclide attached to Substance-P, which accumulates in glioma cells, and intravenously with ⁶⁸ Ga attached to the PSMA-11 ligand, which is selective to glioma cells and salivary glands. The ⁶⁸ Ga radionuclide is routinely used in PET for detecting radiopharmaceutical accumulation and was applied for positronium imaging because it can emit an additional prompt gamma. The prompt gamma enables the determination of the time of positronium formation, while the photons from positronium annihilation were used to reconstruct the place and time of its decay. The determined positronium mean lifetime in glioblastoma cells is shorter than in salivary glands, which in turn is shorter than in healthy brain tissues, demonstrating for the first time that positronium imaging can be used to diagnose disease in vivo . This study also demonstrates that if current total-body PET systems were equipped with multiphoton detection capability and the ⁴⁴ Sc radionuclide was applied, it would be possible to perform positronium imaging at 6500 times greater sensitivity than achieved in this research. Therefore, it is anticipated that positronium imaging has the potential to bring a new quality of cancer diagnosis in clinics.