Editorial Board Spotlights 23 Advances Redefining Radiochemistry and Radiopharmacy

The Editorial Board of EJNMMI Radiopharmacy and Chemistry has released its biannual highlight commentary, a collaborative survey in which each co-authoring board member selected one article from the radiochemistry, radiopharmacy and imaging agent literature published between January and June 2026. The result is a sweeping snapshot of 23 topics spanning novel radiochemistry, proof-of-concept studies, and preclinical and early clinical work with new radiopharmaceuticals, together demonstrating how rapidly the field is progressing across its entire scope.

Among the most chemically striking selections is a systematic study of porphyrins as copper chelators. Using seven structurally distinct porphyrins, researchers compared metalation kinetics and product stability in water at room temperature, conditions directly relevant to radiopharmaceutical preparation, and found that copper inserts into porphyrin macrocycles more readily and forms more persistent complexes than many competing biologically relevant metal ions. The finding gives a fundamental coordination chemistry rationale for why copper-porphyrin systems can be robust radiopharmaceutical platforms, and it supports further development of copper-64-labelled porphyrins for PET imaging and copper-67 analogues for targeted radionuclide therapy, particularly as theranostic pairs. The work addresses a central challenge in radiochemistry: maintaining kinetic and thermodynamic stability of radiometal complexes in vivo, where even highly stable complexes may undergo slow trans-chelation to proteins such as albumin.

Diagnostic tracer design also featured prominently. A structure-guided modification of the FAPI-46 scaffold, introducing an N-methyl-benzenesulfonic acid side chain to increase hydrophilicity, produced the radioligand [18F]AlF-NOTA-GL01, which showed rapid urinary and low hepatobiliary excretion, favourable for imaging abdominal FAP-rich tumours. The increased polarity did not compromise binding: the tracer exhibited higher FAP binding affinity, with an IC50 of 2.94 nM, and greater metabolic stability than [18F]FAPI-42. In patients with confirmed solid tumours, tumour uptake remained high up to 120 minutes post-injection and displayed higher target-to-background ratios than both [18F]FDG and [18F]FAPI-42, with high tumour accumulation blocked by FAPI-42 confirming binding specificity.

Infection imaging took a notable step forward with a synthetic enterobactin analogue called TREN-CAM, characterised by the group of Eszter Boros. Siderophores are low molecular weight iron chelators and well-known virulence factors of pathogenic bacteria, and replacing their iron with gallium-68 enables PET imaging of bacterial metabolism. The team demonstrated specific and highly efficient uptake of [68Ga]GaIII-TREN-CAM, better than [68Ga]GaIII-DFO for some gram-negative bacteria, and improved selective targeting of infection in vivo over [68Ga]GaIII-enterobactin. Crucially, the tracer enabled imaging of treatment response after cefiderocol, a novel antibiotic with a siderophore-mediated mechanism, in a mouse model of E. coli infection, showing the concept’s potential for monitoring novel antibiotic treatments.

Radiofluorination methodology advanced on two fronts. A late-stage, transition metal-free radiofluorination method using triarylselenonium triflates exploits selenium’s greater electrophilicity and leaving-group capacity compared with sulfur, avoiding the residual-metal complications that copper, palladium or nickel methods can introduce into HPLC purification and quality assurance. Yields were generally higher for the selenonium triflates than for corresponding triphenylsulfonium triflates in head-to-head comparisons, and the approach was showcased in the radiosynthesis of the mGluR5 radiotracer [18F]FPEB and an 18F-labelled canagliflozin fragment. Separately, a deaminative cross-electrophile coupling strategy uses nickel catalysis to join 18F-labelled fluoro(hetero)aryl iodides with alkyl pyridinium salts derived from amines, delivering radiochemical conversions of up to 86 percent. Applied to a glycogen synthase kinase-3 inhibitor, the method generated six distinct 18F-labelled analogues from a single common precursor, and one analogue was produced at giga-becquerel levels using semi-automated and fully-automated protocols across three commercial radiosynthesis platforms.

Neurodegeneration research gained new tools as well. A first-in-human study of [18F]FSW-100, an HDAC6 PET tracer, showed that the tracer was well tolerated with good brain uptake in a cohort of healthy male volunteers, offering a more accessible alternative to [18F]bavarostat, whose use has been limited by manufacturing complexity. Work is underway to assess test-retest variability in male and female cohorts and to confirm selectivity over the related enzyme MBLAC2. In a separate Nature Communications study, researchers combining SV2A PET imaging, an in vivo marker of synaptic density, with connectome data from amyloid-positive Alzheimer’s participants and controls showed that brain regions with stronger connectivity displayed more similar levels of synaptic loss, and that an epicenter-based model linked connectivity to both greater cross-sectional synaptic loss and faster longitudinal decline, with plasma phosphorylated tau181 associated with stronger connectivity-mediated synaptic loss.

Therapeutic innovation ran through several selections. A stearic acid-modified, PSMA-targeting peptide-drug conjugate named PDC-C18, which carries the cytotoxic payload monomethyl auristatin E via a cathepsin B-cleavable linker, rapidly forms stable nanocomplexes with human serum albumin while maintaining PSMA specificity, demonstrating a greater than 160-fold longer half-life, a 1.92-fold increase in mean residence time, and a 60-fold reduction in clearance compared with PIBA-modified PDCs, with a reported 96.91 percent tumour suppression rate in the study. The PRINCE trial, a single-arm phase 1b/2 study, examined [177Lu]Lu-PSMA-617 combined with pembrolizumab in metastatic castration-resistant prostate cancer, finding the combination safe with a PSA50 response rate of 76 percent, radiographic progression-free survival of 11.2 months, and overall survival of 20.8 months, results the commentary notes must be considered carefully given the study design and patient number, and which appear comparable to previous radioligand monotherapy trials. A phase 0 imaging trial of [203Pb]Pb-VMT-α-NET, a SPECT/CT surrogate for the paired alpha-therapy isotope 212Pb, achieved 94 percent sensitivity for neuroendocrine tumour lesions larger than 1 cm and enabled quantitative dosimetry supporting individualised treatment planning.

Production chemistry and radiotheranostic matching also advanced. An upscaled approach using enriched cobalt selenide targets and dry distillation enabled robust production of bromine-76 and bromine-77 for a radiolabelled PARP inhibitor, with copper-mediated radiolabelling of a Bpin precursor progressing with excellent yields; the relatively long 57-hour half-life of bromine-77 allows long-distance shipping despite production being limited to few sites. For antibody radiotheranostics, researchers overcame the long-standing chemical mismatch between 89Zr-immunoPET agents labelled with deferoxamine and therapeutic radioimmunoconjugates labelled with DTPA or DOTA, using oxalate-free 89ZrCl4 to enable direct labelling of CHX-A″-DTPA-antibody conjugates in a 10-minute reaction accommodating activities up to 3.4 GBq, producing chelator-matched 89Zr/177Lu/161Tb pairs whose biodistribution more closely matched the therapeutic counterpart in a xenograft model. On the supply side, work on palladium-103 showed that using recycled rhodium target material, from which palladium impurities had been removed, achieved the highest molar activity, underscoring that removing stable carrier isotopes before irradiation is essential for no-carrier-added radiochemicals.

Regulatory and conceptual horizons rounded out the commentary. A European Medicines Agency horizon-scanning report highlighted that approximately 70 radiopharmaceuticals are approved by the FDA and around 20 by the EMA, with 75 to 80 percent intended for diagnostic applications, and that most products approaching marketing authorization are labelled with 177Lu, 68Ga or 18F, while key challenges include the lack of harmonised regulation across Europe and radionuclide supply shortages. A Perspective article on covalent radiopharmaceuticals described how electrophilic warheads can irreversibly anchor radioligands to their targets after binding, including a SuFEx-engineered FAP inhibitor that achieved markedly enhanced tumour uptake and retention over its parent tracer in mice, though the field still faces challenges in controlling off-target reactivity, demonstrating long-term safety and establishing regulatory frameworks. From biorthogonally activated MRI probes with a 200-fold turn-on in relaxivity, to beta-hairpin-stabilised PD-L1 peptides with picomolar affinity, to a pre-targeting PET strategy detecting the procoagulant state associated with Alzheimer’s disease, the board’s collective message is clear: radiochemistry and radiopharmacy are advancing on every front at once, from the chelator to the clinic.

Subject of Research: A biannual editorial board commentary highlighting 23 selected advances in radiochemistry and radiopharmacy published between January and June 2026.

Article Title: Highlight selection of radiochemistry and radiopharmacy developments by editorial board

Article References: Spreckelmeyer, S., DaSilva, J., Decristoforo, C., Mach, R. H., Passchier, J., Carlucci, G., Duatti, A., Cornelissen, B. T., Denkova, A., Hendrikx, J., Seimbille, Y., Yang, X., Jia, H., Zhang, M.-R., Perk, L., Caravan, P., Zeevaart, J. R., Leenhardt, J., Pellico, J., … Yang, M. (2026). Highlight selection of radiochemistry and radiopharmacy developments by editorial board. EJNMMI Radiopharmacy and Chemistry, 11(1), Article 74. https://doi.org/10.1186/s41181-026-00505-4

Image Credits: AI Generated

DOI: 10.1186/s41181-026-00505-4

Keywords: radiochemistry, radiopharmacy, PET imaging, radiopharmaceuticals, theranostics, radionuclide therapy, radiofluorination, copper-64, gallium-68, lutetium-177, PSMA, molecular imaging