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Open research questions in Radiopharmaceutical Chemistry and Applications

63 unresolved questions extracted from the limitations and future-work sections of 151 Radiopharmaceutical Chemistry and Applications papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Effective decorporation strategies for internal 137Cs contamination remain essential. The approved commercial countermeasure, Radiogardase-Cs, may not be optimal.

    Prussian Blue Nanoparticles and Their Potential for the Treatment of Internal 137Cs Contamination in Mice · 2026 · DOI

  • The study is limited by the heterogeneity of included studies. The study is also limited by the lack of patient-level or consistently reported variance data. The study highlights the need for more high-quality economic evaluations in the field.

    Assessing Value for Money in Theranostic Nuclear Medicine: A Systematic Review · 2026 · DOI

  • The field of theranostic nuclear medicine lacks comprehensive cost-effectiveness analyses. There is a need for more standardized and transparent reporting of economic evaluations in the field. The study highlights the importance of considering cost-effectiveness in theranostic nuclear medicine.

    Assessing Value for Money in Theranostic Nuclear Medicine: A Systematic Review · 2026 · DOI

  • The debate on the optimal method to select, monitor and follow patients up. The lack of universal consensus on how to define and assess response on PSMA-PET.

    Chrónos and Káiros in theragnostics: re-assessing time toxicity in final-line radiopharmaceutical treatments · 2026 · DOI

  • There is a need for continued optimisation of ELPs as carriers for radiopharmaceutical delivery. There is a need for systematic evaluation of biosafety, immunogenicity, repeat-dose effects, and regulatory requirements.

    Elastin-like polypeptides in radiopharmaceutical delivery: current evidence, design principles, and translational challenges · 2026 · DOI

  • Limited supply of 211At. Regulatory complexity. Insufficient workforce readiness. Technical challenges in 211At processing.

    211At targeted alpha therapy in Europe: overcoming clinical, regulatory, and infrastructure challenges · 2026 · DOI

  • The paper identifies the need to establish reliable distribution networks capable of safe and timely radiopharmaceutical delivery with ability for 'upscaling' to meet rapid increases in demand, but does not specify logistics models, distribution infrastructure requirements, or scalability thresholds needed to ensure access across countries with varying nuclear medicine facility availability.

    Radiopharmaceutical Therapy in Oncology: Perspectives from Transatlantic Experts · 2026 · DOI

  • The paper emphasizes that lessons from PSMA regulation and PET imaging may apply to other emerging theranostic targets in prostate cancer and beyond, but does not specify which target proteins (beyond PSMA) should be investigated, what molecular heterogeneity characteristics should be studied, or what translational validation pathways are required for these emerging targets.

    Radiopharmaceutical Therapy in Oncology: Perspectives from Transatlantic Experts · 2026 · DOI

  • Abstract Background Phenanthroline derivatives are well-known chelators in coordination chemistry, but their potential in the rapidly evolving field of targeted radionuclide therapy (TRT) has not yet been explored.

    Radiolabeling efficiency of FENTA chelators and stability of their terbium-161, lutetium-177 and bismuth-213 complexes · 2026 · DOI

  • The influence of generator aging on radiochemical yields has not been systematically reported. Standardized buffer systems and systematic optimization of ligand concentration have not been described.

    Long-Term Retrospective Evaluation of Radiochemical Yield Reproducibility of ⁶⁸Ga-Radiopharmaceuticals Using an SiO₂-Based ⁶⁸Ge/⁶⁸Ga Generator · 2026 · DOI

  • Current PSMA ligands demonstrate suboptimal binding stability and limited tumor retention. There is a need for next-generation PSMA ligands with improved PSMA affinity and radiometal coordination efficiency.

    In Silico Optimization of Novel PSMA-Targeted Ligands for Actinium-225 Radiotheranostic Therapy · 2026 · DOI

  • Kulkarni; BAMF Health, Grand Rapids, MI Purpose/Objective(s): Post-therapy SPECT/CT after treatment with Lu- 177 PSMA-617 for metastatic prostate cancer (PC) enables a quantitative whole-body assessment of tumor burden and uptake; however, the relative prognostic value of lesion-level metrics for subsequent lesion response remains uncertain.

    64Cu-anti-CEA M5A PET Imaging Pre and Post Neoadjuvant Radiotherapy in Advanced Rectal Cancer · 2026 · DOI

  • The paper does not provide a detailed analysis of the potential limitations of the method, but mentions that the exact thorium content of the original thorium nitrate samples is not required. The paper also mentions that the method has been tested on a limited number of samples, with a total mass of 350 g.

    An infinite actinium-228 generator as an indispensable tool for nuclear medicine purposes · 2026 · DOI

  • The production of 225Ac is limited by complexity and scarcity, with an estimated 67 GBq (1.8 Ci) per year. The use of 228Ac as a substitute for 225Ac in preclinical studies is limited by the lack of a reliable source. The paper identifies a need for a simple and effective method for the repeated separation of 228Ac from aged thorium nitrate.

    An infinite actinium-228 generator as an indispensable tool for nuclear medicine purposes · 2026 · DOI

  • Priority directions include cleavable-linker engineering, adaptive dosimetry, immunoradiotherapy combinations, industrial radionuclide scalability, and global workforce training. Alpha-emitter platform evolution and modular click-chemistry pretargeting systems are potential areas of research. Combination immunoradiotherapeutic synergy strategies and global clinical deployment infrastructure are also potential areas of research.

    Radioligand theranostics in oncology: emerging trends in target design and radiochemical innovation · 2026 · DOI

  • The need for precise, patient-specific treatment strategies continues to grow. Conventional treatment modalities often suffer from limitations such as systemic toxicity, therapeutic resistance, and lack of tumor specificity. A unified mechanistic synthesis linking target biology, radiochemistry platform selection, and translational feasibility is lacking.

    Radioligand theranostics in oncology: emerging trends in target design and radiochemical innovation · 2026 · DOI

  • Measuring the uptake in vertebrae located near high-uptake organs is challenging. High noise levels and limited number of vertebral cavities can affect the accuracy of bone marrow absorbed dose estimates. The study's findings are limited by the small sample size and the use of a single SPECT/CT camera.

    Multiple vertebrae improves precision in image-based bone marrow absorbed dose estimation in [177Lu]Lu–DOTATATE treatment · 2026 · DOI

  • The study has a limited sample size of 16 patients. The study only analyzes data from a single SPECT/CT camera. The study does not account for other factors that may affect bone marrow absorbed dose estimates, such as patient anatomy and physiology.

    Multiple vertebrae improves precision in image-based bone marrow absorbed dose estimation in [177Lu]Lu–DOTATATE treatment · 2026 · DOI

  • One challenge is the potential for radiation side effects on bone marrow or other normal organs. Another challenge is the need to optimize the pharmacokinetic and radiation delivery properties of intact antibodies and fragments.

    177Lu-labeled anti-TROP2 antibody and its F(ab’)2 fragment for radioimmunotherapy of lung cancer: preparation and biological evaluation · 2026 · DOI

  • Future studies should investigate the therapeutic efficacy of the 177Lu-labeled anti-TROP2 antibody and its F(ab')2 fragment. Further research is needed to optimize the radioligand therapy strategies.

    177Lu-labeled anti-TROP2 antibody and its F(ab’)2 fragment for radioimmunotherapy of lung cancer: preparation and biological evaluation · 2026 · DOI

  • The production of 86Y and 90Y radionuclides using particle-induced reactions is not well optimized. The role of Q-values in optimizing radionuclide production is not fully understood.

    Nuclear Cross Section Evaluation in Particles Induced Reactions on 87Sr and 89Sr for Optimal Production of 86Y And 90Y Radionuclides · 2026 · DOI

  • The development of additional medium-energy α-beam cyclotrons and coordinated production networks. The investigation of new radiochemistry techniques and automated synthesis modules. The establishment of GMP-compliant clean rooms and qualified QC labs.

    211At targeted alpha therapy in Europe: overcoming clinical, regulatory, and infrastructure challenges · 2026 · DOI

  • The paper identifies a gap in considering the time-toxicity of theragnostic agents. There is a need to identify potential areas to minimize time-toxicity.

    Chrónos and Káiros in theragnostics: re-assessing time toxicity in final-line radiopharmaceutical treatments · 2026 · DOI

  • The production yield of 177Lu using a compact cyclotron is lower than that of reactor production. Cyclotron irradiations can be extended to 24-72 hours, limited primarily by target cooling capacity and radiation damage considerations. The use of a compact cyclotron for the production of 177Lu is limited by the availability of the cyclotron and the expertise required for operation.

    Comparison of TALYS and EMPIRE results for 177Lu production yield assessment using Deuteron Particles from compact cyclotron · 2026 · DOI

  • To optimize the production process of 177Lu using a compact cyclotron. To investigate the use of other radioisotopes for medical applications. To develop new methods for the calculation of cross-section amounts using the TALYS and EMPIRE codes.

    Comparison of TALYS and EMPIRE results for 177Lu production yield assessment using Deuteron Particles from compact cyclotron · 2026 · DOI

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63 open questions have been extracted from the limitations and future-work passages of 151 Radiopharmaceutical Chemistry and Applications papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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