The Impact of PET and SPECT on Dosimetry for Targeted Radionuclide Therapy

Background: Radionuclides emitting Auger electrons (AEs) with low (0.02–50 keV) energy, short (0.0007–40 µm) range, and high (1–10 keV/µm) linear energy transfer may have an important role in the targeted radionuclide therapy of metastatic and disseminated disease. Erbium-165 is a pure AE-emitting radionuclide that is chemically matched to clinical therapeutic radionuclide 177Lu, making it a useful tool for fundamental studies on the biological effects of AEs. This work develops new biomedical cyclotron irradiation and radiochemical isolation methods to produce 165Er suitable for targeted radionuclide therapeutic studies and characterizes a new such agent targeting prostate-specific membrane antigen. Methods: Biomedical cyclotrons proton-irradiated spot-welded Ho(m) targets to produce 165Er, which was isolated via cation exchange chromatography (AG 50W-X8, 200–400 mesh, 20 mL) using alpha-hydroxyisobutyrate (70 mM, pH 4.7) followed by LN2 (20–50 µm, 1.3 mL) and bDGA (50–100 µm, 0.2 mL) extraction chromatography. The purified 165Er was radiolabeled with standard radiometal chelators and used to produce and characterize a new AE-emitting radiopharmaceutical, [165Er]PSMA-617. Results: Irradiation of 80–180 mg natHo targets with 40 µA of 11–12.5 MeV protons produced 165Er at 20–30 MBq·µA−1·h−1. The 4.9 ± 0.7 h radiochemical isolation yielded 165Er in 0.01 M HCl (400 µL) with decay-corrected (DC) yield of 64 ± 2% and a Ho/165Er separation factor of (2.8 ± 1.1) · 105. Radiolabeling experiments synthesized [165Er]PSMA-617 at DC molar activities of 37–130 GBq·µmol−1. Conclusions: A 2 h biomedical cyclotron irradiation and 5 h radiochemical separation produced GBq-scale 165Er suitable for producing radiopharmaceuticals at molar activities satisfactory for investigations of targeted radionuclide therapeutics. This will enable fundamental radiation biology experiments of pure AE-emitting therapeutic radiopharmaceuticals such as [165Er]PSMA-617, which will be used to understand the impact of AEs in PSMA-targeted radionuclide therapy of prostate cancer.

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Organs dosimetry in targeted radionuclide therapy

Radiation Physics and Chemistry ◽

10.1016/j.radphyschem.2021.109668 ◽

2021 ◽

pp. 109668

Author(s):

Meshari Alnaaimi ◽

Abdelmoneim Sulieman ◽

Mohammed Alkhorayef ◽

Hasan Salah ◽

Musa Alduaij ◽

...

Keyword(s):

Radionuclide Therapy ◽

Targeted Radionuclide Therapy

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211At-Labeled Polymer Nanoparticles for Targeted Radionuclide Therapy of Glucose-Dependent Insulinotropic Polypeptide Receptor (GIPR)-Overexpressed Cancer

Bioconjugate Chemistry ◽

10.1021/acs.bioconjchem.1c00263 ◽

2021 ◽

Author(s):

Xiumin Shi ◽

Qing Li ◽

Lulu Zhang ◽

Masayuki Hanyu ◽

Lin Xie ◽

...

Keyword(s):

Radionuclide Therapy ◽

Polymer Nanoparticles ◽

Targeted Radionuclide Therapy

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Cellular dosimetry of [177Lu]Lu-DOTA-[Tyr3]octreotate radionuclide therapy: the impact of modeling assumptions on the correlation with in vitro cytotoxicity

EJNMMI Physics ◽

10.1186/s40658-020-0276-5 ◽

2020 ◽

Vol 7 (1) ◽

Cited By ~ 1

Author(s):

Giulia Tamborino ◽

Marijke De Saint-Hubert ◽

Lara Struelens ◽

Dayana C. Seoane ◽

Eline A. M. Ruigrok ◽

...

Keyword(s):

Radionuclide Therapy ◽

In Vitro Cytotoxicity ◽

Cellular Dosimetry ◽

The Impact

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Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

Pharmaceuticals ◽

10.3390/ph14070626 ◽

2021 ◽

Vol 14 (7) ◽

pp. 626

Author(s):

Julie Bolcaen ◽

Shankari Nair ◽

Cathryn H. S. Driver ◽

Tebatso M. G. Boshomane ◽

Thomas Ebenhan ◽

...

Keyword(s):

Tyrosine Kinase ◽

Receptor Tyrosine Kinase ◽

Tyrosine Kinases ◽

Radionuclide Therapy ◽

Kinase Inhibitors ◽

Nuclear Imaging ◽

Therapy Resistance ◽

Targeted Radionuclide Therapy ◽

Therapy Strategy ◽

Dismal Prognosis

Glioblastoma (GB) remains the most fatal brain tumor characterized by a high infiltration rate and treatment resistance. Overexpression and/or mutation of receptor tyrosine kinases is common in GB, which subsequently leads to the activation of many downstream pathways that have a critical impact on tumor progression and therapy resistance. Therefore, receptor tyrosine kinase inhibitors (RTKIs) have been investigated to improve the dismal prognosis of GB in an effort to evolve into a personalized targeted therapy strategy with a better treatment outcome. Numerous RTKIs have been approved in the clinic and several radiopharmaceuticals are part of (pre)clinical trials as a non-invasive method to identify patients who could benefit from RTKI. The latter opens up the scope for theranostic applications. In this review, the present status of RTKIs for the treatment, nuclear imaging and targeted radionuclide therapy of GB is presented. The focus will be on seven tyrosine kinase receptors, based on their central role in GB: EGFR, VEGFR, MET, PDGFR, FGFR, Eph receptor and IGF1R. Finally, by way of analyzing structural and physiological characteristics of the TKIs with promising clinical trial results, four small molecule RTKIs were selected based on their potential to become new therapeutic GB radiopharmaceuticals.

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

Pharmaceutics ◽

10.3390/pharmaceutics13050599 ◽

2021 ◽

Vol 13 (5) ◽

pp. 599

Author(s):

Stephen Ahenkorah ◽

Irwin Cassells ◽

Christophe M. Deroose ◽

Thomas Cardinaels ◽

Andrew R. Burgoyne ◽

...

Keyword(s):

Cancer Treatment ◽

Radionuclide Therapy ◽

Chemical Properties ◽

High Energy ◽

Magic Bullet ◽

Targeted Radionuclide Therapy ◽

Energy Photon ◽

Normal Tissues ◽

Preclinical And Clinical Studies ◽

Alpha Therapy

In contrast to external high energy photon or proton therapy, targeted radionuclide therapy (TRNT) is a systemic cancer treatment allowing targeted irradiation of a primary tumor and all its metastases, resulting in less collateral damage to normal tissues. The α-emitting radionuclide bismuth-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 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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