Design and Challenges of Radiopharmaceuticals

Vermeulen, Koen; Vandamme, Mathilde; Bormans, Guy; Cleeren, Frederik

doi:10.1053/j.semnuclmed.2019.07.001

Cited by 100 publications

(71 citation statements)

References 114 publications

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“…Though, the tumor uptake vs A m may be bell shaped when targeting tumors with diagnostic radiopeptides. If too few molecules are administered (high A m ), a large fraction of the radiotracer can be trapped during its first pass effect by high-affinity low-capacity binding sites in non-target organs such as the liver, and will not reach their target (Vermeulen et al 2019). Therefore, we opted to perform a cartridge purification instead of an HPLC purification.…”

Section: Radiochemistrymentioning

confidence: 99%

Automated GMP compliant production of [18F]AlF-NOTA-octreotide

Tshibangu

Cawthorne

Serdons

et al. 2020

EJNMMI radiopharm. chem.

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Background: Gallium-68 labeled synthetic somatostatin analogs for PET/CT imaging are the current gold standard for somatostatin receptor imaging in neuroendocrine tumor patients. Despite good imaging properties, their use in clinical practice is hampered by the low production levels of 68 Ga eluted from a 68 Ge/ 68 Ga generator. In contrast, 18 F-tracers can be produced in large quantities allowing centralized production and distribution to distant PET centers. [ 18 F]AlF-NOTA-octreotide is a promising tracer that combines a straightforward Al 18 F-based production procedure with excellent in vivo pharmacokinetics and specific tumor uptake, demonstrated in SSTR2 positive tumor mice. However, advancing towards clinical studies with [ 18 F]AlF-NOTA-octreotide requires the development of an efficient automated GMP production process and additional preclinical studies are necessary to further evaluate the in vivo properties of [ 18 F]AlF-NOTA-octreotide. In this study, we present the automated GMP production of [ 18 F]AlF-NOTA-octreotide on the Trasis AllinOne® radio-synthesizer platform and quality control of the drug product in accordance with GMP. Further, radiometabolite studies were performed and the pharmacokinetics and biodistribution of [ 18 F]AlF-NOTA-octreotide were assessed in healthy rats using μPET/MR. Results: The production process of [ 18 F]AlF-NOTA-octreotide has been validated by three validation production runs and the tracer was obtained with a final batch activity of 10.8 ± 1.3 GBq at end of synthesis with a radiochemical yield of 26.1 ± 3.6% (dc), high radiochemical purity and stability (96.3 ± 0.2% up to 6 h post synthesis) and an apparent molar activity of 160.5 ± 75.3 GBq/μmol. The total synthesis time was 40 ± 3 min. Further, the quality control was successfully implemented using validated analytical procedures. Finally, [ 18 F]AlF-NOTA-octreotide showed high in vivo stability and favorable pharmacokinetics with high and specific accumulation in SSTR2expressing organs in rats. Conclusion: This robust and automated production process provides high batch activity of [ 18 F]AlF-NOTA-octreotide allowing centralized production and shipment of the compound to remote PET centers. Further, the production process and quality control developed for [ 18 F]AlF-NOTA-octreotide is easily implementable in a clinical setting and the tracer is a potential clinical alternative for somatostatin directed 68 Ga labeled peptides obviating the need for a 68 Ge/ 68 Ga-generator. Finally, the favorable in vivo properties of [ 18 F]AlF-NOTA-octreotide in rats, with high and specific accumulation in SSTR2 expressing organs, supports clinical translation.

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Section: Radiochemistrymentioning

confidence: 99%

Automated GMP compliant production of [18F]AlF-NOTA-octreotide

Tshibangu

Cawthorne

Serdons

et al. 2020

EJNMMI radiopharm. chem.

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“…Nuclear medicine plays an important role in the diagnosis, follow-up, and treatment of cancer patients. Radiopharmaceuticals consist conceptually up to three functional elements: 1) a vector (or carrier) molecule with high affinity and selectivity for the target; 2) a radionuclide and 3) a linker or chelator to attach the former to the latter [1][2][3][4] (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Bismuth-213 for Targeted Radionuclide Therapy: From Atom to Bedside

Ahenkorah¹,

Cassells²,

Deroose³

et al. 2021

Preprint

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Besides external high-energy photon or proton beam therapy, targeted radionuclide therapy (TRNT) is an alternative approach to deliver radiation to cancer cells. TRNT is distributed within the body by the vascular system and allows targeted irradiation of a primary tumor and all its metastases, resulting in substantially less collateral damage to normal tissues as compared to ex-ternal beam radiotherapy (EBRT). It is a systemic cancer therapy, tackling systemic spread of the disease, which is the cause of death in most cancer patients. The α-emitting radionuclide bis-muth-213 (213Bi) has interesting properties and can be considered as a magic bullet for TRNT. The benefits and drawbacks of targeted alpha therapy with 213Bi are discussed in this review, covering the entire chain from radionuclide production to bedside. First, the radionuclide properties and production of 225Ac and its daughter 213Bi are discussed, followed by the fundamental chemical properties of bismuth. Next, an overview of available acyclic and macrocyclic bifunctional chelators for bismuth, and general considerations for designing a 213Bi-radiopharmaceutical are provided. Finally, we will provide an overview of preclinical and clinical studies involving 213Bi-radiopharmaceuticals, as well as the future perspectives of this promising cancer treatment option.

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“…The nanobeads were radiolabelled by reacting eluent from a 99 Mo/ 99m Tc generator with the polymer prefunctionalized with magnetite in presence of SnCl 2 , as shown in Figure 5B. Similarly, 99m Tc‐, 68 Ga‐, or 18 F‐labelled MAA particles of 10–100 mm, trapped in the first downstream capillary from site of administration, are used for lung perfusion and shunt estimation 138,139 . 64 Cu‐labelled poly(aspartic acid)‐coated iron oxide conjugated to RGD peptide nanoparticles have been developed for integrin recognition 140 .…”

Section: Different Nanoparticle Systems Used For Delivery Of Radiophamentioning

confidence: 99%

“…Presently, scant consideration is given to develop reliable 3D models for comparative preclinical testing of nanoparticle radiopharmaceuticals. Different countries have different dossier and GMP instructions; however, a common document for practical guidance can be obtained from the International Atomic Energy Agency (IAEA) 139 . However, it appears certain that if the fundamental behaviour of nanoparticles in human body is standardized, they can contribute immensely to radiopharmaceutical development.…”

Section: Current Challenges and Future Perspectivesmentioning

confidence: 99%

Nanoparticulate formulations of radiopharmaceuticals: Strategy to improve targeting and biodistribution properties

Datta

Ray

2020

Labelled Comp Radiopharmac

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Application of nanotechnology principles in drug delivery has created opportunities for treatment of several diseases. Nanotechnology offers the advantage of overcoming the adverse biopharmaceutics or pharmacokinetic properties of drug molecules, to be determined by the transport properties of the particles themselves. Through the manipulation of size, shape, charge, and type of nanoparticle delivery system, variety of distribution profiles may be obtained. However, there still exists greater need to derive and standardize definitive structure property relationships for the distribution profiles of the delivery system. When applied to radiopharmaceuticals, the delivery systems assume greater significance. For the safety and efficacy of both diagnostics and therapeutic radiopharmaceuticals, selective localization in target tissue is even more important. At the same time, the synthesis and fabrication reactions of radiolabelled nanoparticles need to be completed in much shorter time. Moreover, the extensive understanding of the several interesting optical and magnetic properties of materials in nanoscale provides for achieving multiple objectives in nuclear medicine. This review discusses the various nanoparticle systems, which are applied for radionuclides and analyses the important bottlenecks that are required to be overcome for their more widespread clinical adaptation.

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Design and Challenges of Radiopharmaceuticals

Cited by 100 publications

References 114 publications

Automated GMP compliant production of [18F]AlF-NOTA-octreotide

Automated GMP compliant production of [18F]AlF-NOTA-octreotide

Bismuth-213 for Targeted Radionuclide Therapy: From Atom to Bedside

Nanoparticulate formulations of radiopharmaceuticals: Strategy to improve targeting and biodistribution properties

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