Diagnostic and Therapeutic Radiopharmaceuticals

Lindsley, Craig W.; Müller, Christian; Bongarzone, Salvatore

doi:10.1021/acs.jmedchem.2c01403

Cited by 5 publications

(2 citation statements)

References 49 publications

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“…2022 ; Sgouros 2019 ; Lindsley et al. 2022 ; Sgouros 2023 ; Pallares and Abergel 2022 ). This vastly emerging paradigm has led to significant excitement, while there is a significant number of phenomena that need to be better understood towards optimal, personalized, and precision RPTs (Siebinga et al.…”

Section: Introductionmentioning

confidence: 98%

Physiologically based radiopharmacokinetic (PBRPK) modeling to simulate and analyze radiopharmaceutical therapies: studies of non-linearities, multi-bolus injections, and albumin binding

Fele-Paranj,

Saboury,

Uribe

et al. 2024

EJNMMI radiopharm. chem.

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Background We aimed to develop a publicly shared computational physiologically based pharmacokinetic (PBPK) model to reliably simulate and analyze radiopharmaceutical therapies (RPTs), including probing of hot-cold ligand competitions as well as alternative injection scenarios and drug designs, towards optimal therapies. Results To handle the complexity of PBPK models (over 150 differential equations), a scalable modeling notation called the “reaction graph” is introduced, enabling easy inclusion of various interactions. We refer to this as physiologically based radiopharmacokinetic (PBRPK) modeling, fine-tuned specifically for radiopharmaceuticals. As three important applications, we used our PBRPK model to (1) study the effect of competition between hot and cold species on delivered doses to tumors and organs at risk. In addition, (2) we evaluated an alternative paradigm of utilizing multi-bolus injections in RPTs instead of prevalent single injections. Finally, (3) we used PBRPK modeling to study the impact of varying albumin-binding affinities by ligands, and the implications for RPTs. We found that competition between labeled and unlabeled ligands can lead to non-linear relations between injected activity and the delivered dose to a particular organ, in the sense that doubling the injected activity does not necessarily result in a doubled dose delivered to a particular organ (a false intuition from external beam radiotherapy). In addition, we observed that fractionating injections can lead to a higher payload of dose delivery to organs, though not a differential dose delivery to the tumor. By contrast, we found out that increased albumin-binding affinities of the injected ligands can lead to such a differential effect in delivering more doses to tumors, and this can be attributed to several factors that PBRPK modeling allows us to probe. Conclusions Advanced computational PBRPK modeling enables simulation and analysis of a variety of intervention and drug design scenarios, towards more optimal delivery of RPTs.

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Section: Introductionmentioning

confidence: 98%

Physiologically based radiopharmacokinetic (PBRPK) modeling to simulate and analyze radiopharmaceutical therapies: studies of non-linearities, multi-bolus injections, and albumin binding

Fele-Paranj,

Saboury,

Uribe

et al. 2024

EJNMMI radiopharm. chem.

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“…3 ) [ 55 ]. Radiopharmaceuticals are biologically active molecules labelled by radionuclides that provide a source of ionizing radiation mainly applied in diagnostic imaging and therapy [ 56 ]. The radiopharmaceutical is administered to the patient before surgery, temporarily making the body a source of radiation to detect with a specific instrument, an intraoperative probe sensitive to the emissions released by the drug [ 55 ].…”

Section: Intraoperative Imaging Modalities To Improve Surgical Precisionmentioning

confidence: 99%

Image-guided cancer surgery: a narrative review on imaging modalities and emerging nanotechnology strategies

et al. 2023

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Surgical resection is the cornerstone of solid tumour treatment. Current techniques for evaluating margin statuses, such as frozen section, imprint cytology, and intraoperative ultrasound, are helpful. However, an intraoperative assessment of tumour margins that is accurate and safe is clinically necessary. Positive surgical margins (PSM) have a well-documented negative effect on treatment outcomes and survival. As a result, surgical tumour imaging methods are now a practical method for reducing PSM rates and improving the efficiency of debulking surgery. Because of their unique characteristics, nanoparticles can function as contrast agents in image-guided surgery. While most image-guided surgical applications utilizing nanotechnology are now in the preclinical stage, some are beginning to reach the clinical phase. Here, we list the various imaging techniques used in image-guided surgery, such as optical imaging, ultrasound, computed tomography, magnetic resonance imaging, nuclear medicine imaging, and the most current developments in the potential of nanotechnology to detect surgical malignancies. In the coming years, we will see the evolution of nanoparticles tailored to specific tumour types and the introduction of surgical equipment to improve resection accuracy. Although the promise of nanotechnology for producing exogenous molecular contrast agents has been clearly demonstrated, much work remains to be done to put it into practice. Graphical Abstract

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An Upgraded Solid‐Phase Assembly of Chelators (DOTA and NOTA) Enabled Bacterial Uptake Studies of Radiolabeled Peptide

Pati,

Kumar,

Chowdhury

et al. 2024

ChemBioChem

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Among popular radio metal chelators, DOTA and NOTA have been remarkably considered in radionuclide therapy and imaging studies due to several advantages in pharmacology. Here, we developed a practical and general method for assembling DOTA and NOTA in the solid phase peptide (pseudo‐dilute conditions) with a wide range of solvents using easily accessible and economical feedstocks, which mitigated unprecedented challenges faced by previously reported methods. This upgraded approach enabled an efficient installation of these two chelators on various bioactive peptide sequences. Finally, we assessed the antimicrobial activity of the DOTA‐ and NOTA‐attached Combi peptides to B. subtilis, which was found to be intact. The authenticity of the assembled DOTA framework was assessed by labeling 177Lu and in vitro bacterial uptake in E. coli and S. aureus. 177Lu‐labeled DOTA‐Combi peptide exhibited promising uptake for developing a bacterial infection imaging agent while negligible hemolysis activity even at > 200 µM. This contribution will be valued for developing peptide radiopharmaceuticals with operational simplicity and economic approaches.

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Diagnostic and Therapeutic Radiopharmaceuticals

Cited by 5 publications

References 49 publications

Physiologically based radiopharmacokinetic (PBRPK) modeling to simulate and analyze radiopharmaceutical therapies: studies of non-linearities, multi-bolus injections, and albumin binding

Physiologically based radiopharmacokinetic (PBRPK) modeling to simulate and analyze radiopharmaceutical therapies: studies of non-linearities, multi-bolus injections, and albumin binding

Image-guided cancer surgery: a narrative review on imaging modalities and emerging nanotechnology strategies

An Upgraded Solid‐Phase Assembly of Chelators (DOTA and NOTA) Enabled Bacterial Uptake Studies of Radiolabeled Peptide

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