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Open research questions in Radiopharmaceutical Chemistry and Applications

111 gap statements mined from Radiopharmaceutical Chemistry and Applications papers in our 4.5M-paper local library, which holds 570 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Future research can focus on improving the energy resolution of the MMC detector. The detector can be used for other applications in nuclear medicine.

    Advancing towards cancer theragnostic by probing the 225Ac decay chain with ultra-high-resolution metallic magnetic calorimeter based detectors · 2026 · DOI

  • Quantitative detection of 225Ac and its daughter radionuclides by γ-spectroscopy has been unattainable. The paper aims to address this gap by using an MMC detector.

    Advancing towards cancer theragnostic by probing the 225Ac decay chain with ultra-high-resolution metallic magnetic calorimeter based detectors · 2026 · DOI

  • Conventional imaging has significant limitations for post-radiopharmaceutical therapy response evaluation. There is a lack of consensus regarding how best to optimally monitor those individuals with CRPC who receive radiopharmaceutical therapies.

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

  • There is a lack of understanding of the molecular differences and biology of treatment targets on cells. There is a need for improved methods for monitoring patients with CRPC who receive radiopharmaceutical therapies.

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

  • PET uptake should not be interpreted as a direct surrogate for absorbed dose in RPT. Discrepancies between PET uptake and CT anatomy can complicate interpretation. Clinical adoption of biologically guided radiotherapy is limited.

    PET-guided therapy: synergies, strategies, and future directions in external beam radiation therapy and radiopharmaceutical therapy · 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

  • 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

  • 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

  • The gap in understanding the pharmacokinetic and radiation delivery properties of intact antibodies and fragments is addressed.

    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 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 lack of coordinated approaches to overcome production, regulatory, and infrastructure challenges. The limited supply of 211At. The restricted clinical evidence generation and regulatory complexity.

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

  • Limited global availability of highly enriched targets. Management of long-lived radioactive by-products. Need for standardized dosimetry and regulatory pathways to ensure reproducibility and safety.

    Emerging Theranostic Radiometals (149Tb, 44Sc, 52Mn, 203Pb, 55Co)—Decay Diversity, Production Landscape, and Translational Imaging · 2026 · DOI

  • 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 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 need to incorporate both physical and chemical processes in the simulation. The challenge of comparing simulation results with experimental data.

    Evaluation of radiation damage effects of low-energy Auger and conversion electrons emitted by 134Ce decay using a Monte Carlo method · 2026 · DOI

  • 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 only investigated two administration routes. The sample size was limited to 20 rats. The study did not investigate the long-term effects of ruxolitinib.

    Radiosynthesis of a novel carbon-11-labeled ruxolitinib analogue and preliminary evaluation of its biodistribution via different routes of administration · 2026 · DOI

  • In vivo evaluation of FENTA chelators with terbium-161 and lutetium-177. Development of new chelators with improved kinetic inertness and radiolabeling efficiency.

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

  • Exploring individualized RPT dosing and EBRT dose escalation based on PET-defined subregions. Investigating the potential of total-body PET (TB-PET) scanners in molecular imaging.

    PET-guided therapy: synergies, strategies, and future directions in external beam radiation therapy and radiopharmaceutical therapy · 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 study did not address the diagnostic aspect - The study did not include experimental validation - The study only considered the radiation damage effects…

    Evaluation of radiation damage effects of low-energy Auger and conversion electrons emitted by 134Ce decay using a Monte Carlo method · 2026 · DOI

Most-cited papers in Radiopharmaceutical Chemistry and Applications

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Open questions raised by papers listed on this page include: (1) Future research can focus on improving the energy resolution of the MMC detector (“Advancing towards cancer theragnostic by probing the 225Ac decay chain with…”, 2026); (2) There is a lack of consensus regarding how best to optimally monitor those individuals with CRPC who receive radiopharmaceutical therapies (“Radiopharmaceutical Therapy in Oncology: Perspectives from Transatlantic Experts”, 2026); (3) The use of 228Ac as a substitute for 225Ac in preclinical studies is limited by the lack of a reliable source (“An infinite actinium-228 generator as an indispensable tool for nuclear…”, 2026); (4) The role of Q-values in optimizing radionuclide production is not fully understood (“Nuclear Cross Section Evaluation in Particles Induced Reactions on 87Sr and…”, 2026); (5) The study is also limited by the lack of patient-level or consistently reported variance data (“Assessing Value for Money in Theranostic Nuclear Medicine: A Systematic Review”, 2026). 111 gap statements have been mined from Radiopharmaceutical Chemistry and Applications papers in our 4.5M-paper local library, which holds 570 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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