An overview of nanoscale radionuclides and radiolabeled nanomaterials commonly used for nuclear molecular imaging and therapeutic functions

Farzin, Leila; Sheibani, Shahab; Moassesi, Mohammad Esmaeil; Shamsipur, Mojtaba

doi:10.1002/jbm.a.36550

Cited by 68 publications

(50 citation statements)

References 237 publications

(554 reference statements)

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“…According to the "magic bullet" ("Zauberkugel") approach proposed by Paul Ehrlich (1900), the cytotoxic payload is delivered selectively to the malignant cells [22]. The vectors can be represented by small molecules, peptides, antibodies, or antibody derivatives, as well as by nanocarriers (as a full review of these would be exceeding the limits of this article, please refer, for instance, to [23][24][25][26][27][28]). [ 223 Ra]RaCl 2 , however, represents an exception due to its intrinsic bone-targeting properties, mimicking the chemical behavior and metabolic pathway of calcium, as both elements belong to the alkali earth metals.…”

Section: Introductionmentioning

confidence: 99%

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

2020

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Atomic in vivo nanogenerators such as actinium-225, thorium-227, and radium-223 are of increasing interest and importance in the treatment of patients with metastatic cancer diseases. This is due to their peculiar physical, chemical, and biological characteristics, leading to astonishing responses in otherwise resistant patients. Nevertheless, there are still a few obstacles and hurdles to be overcome that hamper the broader utilization in the clinical setting. Next to the limited supply and relatively high costs, the in vivo complex stability and the fate of the recoiling daughter radionuclides are substantial problems that need to be solved. In radiobiology, the mechanisms underlying treatment efficiency, possible resistance mechanisms, and late side effect occurrence are still far from being understood and need to be unraveled. In this review, the current knowledge on the scientific and clinical background of targeted alpha therapies is summarized. Furthermore, open issues and novel approaches with a focus on the future perspective are discussed. Once these are unraveled, targeted alpha therapies with atomic in vivo nanogenerators can be tailored to suit the needs of each patient when applying careful risk stratification and combination therapies. They have the potential to become one of the major treatment pillars in modern cancer management.

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Section: Introductionmentioning

confidence: 99%

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

2020

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“…While some studies have been done regarding the application of AuNPs for theranostics, their therapeutic function is mostly based on the photothermal properties of the AuNPs themselves or on the delivery of a payload acting as a cytotoxic drug [40][41][42][43][44][45][46]. There are some examples of AuNPs that have been evaluated in the delivery of medically relevant radionuclides, aiming to obtain "radiotheranostic" agents suitable to provide clear and sensitive tumor detection and selective therapeutic effects [47,48]. This included nanoconstructs decorated with bombesin (BBN) analogues, a bioactive peptide with high affinity towards the Gastrin Releasing Peptide receptor (GRPr) overexpressed in a variety of human cancers, and demonstrated that the AuNPs displayed specificity towards GRPr overexpressing tumors [49][50][51].…”

Section: Introductionmentioning

confidence: 99%

Dual Imaging Gold Nanoplatforms for Targeted Radiotheranostics

et al. 2020

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Gold nanoparticles (AuNPs) are interesting for the design of new cancer theranostic tools, mainly due to their biocompatibility, easy molecular vectorization, and good biological half-life. Herein, we report a gold nanoparticle platform as a bimodal imaging probe, capable of coordinating Gd3+ for Magnetic Resonance Imaging (MRI) and 67Ga3+ for Single Photon Emission Computed Tomography (SPECT) imaging. Our AuNPs carry a bombesin analogue with affinity towards the gastrin releasing peptide receptor (GRPr), overexpressed in a variety of human cancer cells, namely PC3 prostate cancer cells. The potential of these multimodal imaging nanoconstructs was thoroughly investigated by the assessment of their magnetic properties, in vitro cellular uptake, biodistribution, and radiosensitisation assays. The relaxometric properties predict a potential T1- and T2- MRI application. The promising in vitro cellular uptake of 67Ga/Gd-based bombesin containing particles was confirmed through biodistribution studies in tumor bearing mice, indicating their integrity and ability to target the GRPr. Radiosensitization studies revealed the therapeutic potential of the nanoparticles. Moreover, the DOTA chelating unit moiety versatility gives a high theranostic potential through the coordination of other therapeutically interesting radiometals. Altogether, our nanoparticles are interesting nanomaterial for theranostic application and as bimodal T1- and T2- MRI / SPECT imaging probes.

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“…Radiolabeling methods yield nanomaterials used for the therapy and diagnosis of cancers [1][2][3][4][5][6][7][8][9][10] including for therapy of liver cancer (microspheres, arterial infusion), [11][12][13][14][15] and for sentinel lymph node delineation. [16][17][18][19][20][21] Here we examine a wide range of metals including many with radioactive isotopes used for diagnostic imaging or radionuclide therapy, for their ability to bind to the superparamagnetic iron oxide (SPION) nanoparticle (NP) known as Feraheme (FH), a drug approved for treating iron anemia and used off label as an MR contrast agent.…”

Section: Introductionmentioning

confidence: 99%

<p>A Chelate-Free Nano-Platform for Incorporation of Diagnostic and Therapeutic Isotopes</p>

Gholami¹,

Josephson²,

Akam³

et al. 2020

IJN

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Purpose: Using our chelate-free, heat-induced radiolabeling (HIR) method, we show that a wide range of metals, including those with radioactive isotopologues used for diagnostic imaging and radionuclide therapy, bind to the Feraheme (FH) nanoparticle (NP), a drug approved for the treatment of iron anemia. Material and methods: FH NPs were heated (120°C) with nonradioactive metals, the resulting metal-FH NPs were characterized by inductively coupled plasma mass spectrometry (ICP-MS), dynamic light scattering (DLS), and r 1 and r 2 relaxivities obtained by nuclear magnetic relaxation spectrometry (NMRS). In addition, the HIR method was performed with [ 90 Y]Y 3+ , [ 177 Lu]Lu 3+ , and [ 64 Cu]Cu 2+ , the latter with an HIR technique optimized for this isotope. Optimization included modifying reaction time, temperature, and vortex technique. Radiochemical yield (RCY) and purity (RCP) were measured using size exclusion chromatography (SEC) and thin-layer chromatography (TLC). Results: With ICP-MS, metals incorporated into FH at high efficiency were bismuth, indium, yttrium, lutetium, samarium, terbium and europium (>75% @ 120 o C). Incorporation occurred with a small (less than 20%) but statistically significant increases in size and the r 2 relaxivity. An improved HIR technique (faster heating rate and improved vortexing) was developed specifically for copper and used with the HIR technique and [ 64 Cu] Cu 2+. Using SEC and TLC analyses with [ 90 Y]Y 3+ , [ 177 Lu]Lu 3+ and [ 64 Cu]Cu 2+ , RCYs were greater than 85% and RCPs were greater than 95% in all cases. Conclusion: The chelate-free HIR technique for binding metals to FH NPs has been extended to a range of metals with radioisotopes used in therapeutic and diagnostic applications. Cations with f-orbital electrons, more empty d-orbitals, larger radii, and higher positive charges achieved higher values of RCY and RCP in the HIR reaction. The ability to use a simple heating step to bind a wide range of metals to the FH NP, a widely available approved drug, may allow this NP to become a platform for obtaining radiolabeled nanoparticles in many settings.

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An overview of nanoscale radionuclides and radiolabeled nanomaterials commonly used for nuclear molecular imaging and therapeutic functions

Abstract: Recent advances in the field of nanotechnology applications in nuclear medicine offer the promise of better diagnostic and therapeutic options.

Cited by 68 publications

References 237 publications

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

Dual Imaging Gold Nanoplatforms for Targeted Radiotheranostics

<p>A Chelate-Free Nano-Platform for Incorporation of Diagnostic and Therapeutic Isotopes</p>

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