By using solid targets in medical cyclotrons, it is possible to produce large amounts of ⁶⁸GaCl₃. Purification of Ga³⁺ from metal ion impurities is a critical step, as these metals compete with Ga³⁺ in the complexation with different chelators, which negatively affects the radiolabeling yields. In this work, we significantly lowered the level of iron (Fe) impurities by adding ascorbate in the purification, and the resulting ⁶⁸GaCl₃could be utilized for high-yield radiolabeling of clinically relevant DOTA-based tracers. ⁶⁸GaCl₃ was cyclotron-produced and purified with ascorbate added in the wash solutions through the UTEVA resins. The ⁶⁸Ga eluate was analyzed for radionuclidic purity (RNP) by gamma spectroscopy, metal content by ICP-MS, and by titrations with the chelators DOTA, NOTA, and HBED. The ⁶⁸GaCl₃eluate was utilized for GMP-radiolabeling of the DOTA-based tracers DOTATOC and FAPI-46 using an automated synthesis module. DOTA chelator titrations gave an apparent molar activity (AMA) of 491 ± 204 GBq/µmol. GMP-compliant syntheses yielded up to 7 GBq/batch [⁶⁸Ga]Ga-DOTATOC and [⁶⁸Ga]Ga-FAPI-46 (radiochemical yield, RCY ~ 60%, corresponding to ten times higher compared to generator-based productions). Full quality control (QC) of ⁶⁸Ga-labelled tracers showed radiochemically pure and stable products at least four hours from end-of-synthesis.

The growing need and limited availability of generator produced 68Ga (T1/2 = 68 min) for PET has provided the impetus for alternative, high output, 68Ga production routes such as charge particle activation of enriched 68Zn using PET cyclotrons. The work presents a rapid production method for clinically useful 68Ga for radiolabeling. The focus is also to expand the production capacity of cyclotron solid target-produced 68Ga over generator produced and liquid solutions targets by using enriched 68Zn-foils that minimizes target preparation.

Background: In vivo monitoring of cell biodistribution using positron emission tomography (PET) provides a quantitative non-invasive method to further optimize cell therapies and related new developments in the field. Our group has earlier optimized and evaluated the in vitro properties of two radiotracers,[⁸⁹Zr]Zr-(oxinate)₄ and [⁸⁹Zr]Zr-DFO-NCS, for the radiolabelling of different cell types. Here, we performed a microPET study to assess the in vivo biodistribution of cells in rats using these two radiotracers. Human decidual stromal cells (hDSC) and rat macrophages (rMac) were radiolabelled with [⁸⁹Zr]Zr-(oxinate)₄ or [⁸⁹Zr]Zr-DFO-NCS. Rats were intravenously injected with radiolabelled cells, and the in vivo biodistribution was monitored with microPET/CT imaging for up to day 7. Organ uptake was evaluated and presented as a percentage of injected activity per gram tissue (%IA/g) and total absorbed organ doses (mSv/MBq). Results: The biodistribution in vivo showed an immediate uptake in the lungs. Thereafter, [⁸⁹Zr]Zr-(oxinate)₄ labelled cells migrated to the liver, while the signal from [⁸⁹Zr]Zr-DFO-NCS labelled cells lingered in the lungs. The differences in the in vivo behaviour for the same cell type appeared related to the radiotracer labelling. After 24 h, [⁸⁹Zr]Zr-(oxinate)₄ labelled cells had over 70% higher liver uptake for both hDSC and rMac compared to [⁸⁹Zr]Zr-DFO-NCS labelled cells, whereas [⁸⁹Zr]Zr-DFO-NCS labelled cells showed over 60% higher uptake in the lungs compared to [⁸⁹Zr]Zr-(oxinate)₄ labelled cells. This difference in both lung and liver uptake continued until day 7. Dosimetry calculations showed a higher effective dose (mSv/MBq) for [⁸⁹Zr]Zr-DFO-NCS compared to [⁸⁹Zr]Zr-(oxinate)₄, for both cell types. Although the bone uptake was higher for [⁸⁹Zr]Zr-(oxinate)₄ labelled cells, the prolonged uptake in the lungs contributed to a significant crossfire to bone marrow resulting in a higher bone dose. Conclusion: The [⁸⁹Zr]Zr-DFO-NCS labelled cells suggest a prolonged accumulation in the lungs, while [⁸⁹Zr]Zr-(oxinate)₄ suggests quicker clearance of the lungs followed by accumulation in the liver. Accumulation of radiolabelled cells in the liver corresponds to other cell-tracking methods. Further studies are required to determine the actual location of the [⁸⁹Zr]Zr-DFO-NCS labelled cell.

Background: Beyond the use of conventional short-lived PET radionuclides, there is a growing interest in tracking larger biomolecules and exploring radiotheranostic applications. One promising option for imaging medium-sized molecules and peptides is ⁵⁵Co (T₁/₂ = 17.5 h, β⁺ = 76%), which enables imaging of new and already established tracers with blood circulation of several hours. Additionally, ⁵⁵Co can be paired with the Auger-Meitner emitter ^58mCo (T₁/₂ = 9 h, 100% IC) for radiotheranostic applications. Here we report on ⁵⁵Co production via the ⁵⁸Ni(p,α)⁵⁵Co reaction channel using pressed ⁵⁸Ni and Mg matrix targets. Results: This set up is capable to produce and isolate 240 ± 20 MBq [⁵⁵Co]Co^+ 2 (80% RCY) with 4 ml 0.25 M HEPES at 35 min post End Of Bombardment for 3 h, 25 µA protons irradiation. The RNP of the eluate is 99.98 ± 0.014% as measured 2 h & 17 h post EOB. AMA was determined to 1.5 ± 0.5 GBq/µmol [⁵⁵Co]Co-DOTA at EOB. Mg dissolves rapidly in the acid mixture, leaving behind a porous, sponge-like Ni matrix increasing the surface area of the Ni and therefore accelerating the dissolution. Conclusion: We present a novel, simple, and rapid method to produce ⁵⁵Co with pressed ⁵⁸Ni/Mg matrix targets enabling faster target fabrication and dissolution. By using a simple hydraulic press, mechanically stable target coins useful for solid target irradiation are fabricated within 5 min and can be dissolved in 10 min at room temperature. The foils remain intact after irradiation and can endure irradiation conditions providing sufficient activity (> 200 MBq) for clinical doses. The method presented here using Mg as a support metal for fixation of the actual target material into target coins is applicable for other target combinations as well. Using Mg as a support metal is suitable due to its thermal conductivity, low activation, minimal impact on purification chemistry, softness, ductility, and rapid dissolution in acid.

Background: Antibody-drug conjugates (ADCs) are gaining rapidly expanding clinical utility, with a growing number of approved indications across compounds that differ in target antigen, payload mechanism, and linker design. However, treatment response remains heterogeneous, and predictive biomarkers to identify patients most likely to benefit are limited. Given that ADC efficacy depends on sufficient target antigen expression and distribution across tumor lesions, positron emission tomography (PET) imaging offers a unique opportunity to non-invasively assess whole-body target availability. We therefore conducted a systematic literature review to evaluate the relationship between PET-measured tumor antigen expression and the therapeutic response to ADCs targeting the same antigen. Method: A systematic comprehensive search of PubMed, EMBASE and Web of Science databases was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using terms related to targeted PET, ADC treatment and response assessment. Article screening, eligibility assessment, and data extraction were performed independently using predefined criteria by two reviewers. Disagreements were resolved by consensus. Results: A total of 5628 records were identified. After removing duplicates, 4323 records were screened by title and Fifty-eight underwent full-text review and seven were included in the final review. Four trials investigated human epidermal growth factor receptor 2 (HER2)-targeted therapy, one Nectin-4, one mesothelin and one STEAP1. In all HER2- and Nectin-4-related trials, patients with a higher uptake on targeted PET had a higher probability of responding to targeted treatment. Included trials were generally small and had a moderate risk of bias. Conclusion: Targeted PET imaging showed potential to predict treatment response in trials evaluating clinically active agents. Additional clinical trials across a broader range of targets, along with standardized acquisition protocols and harmonized study designs, are needed to enable the integration of this technique into clinical practice and ultimately translate its benefits to patients.