Radio-enhancement effects by radiolabeled nanoparticles

Gholami, Yaser Hadi; Maschmeyer, Richard; Kuncic, Zdenka

doi:10.1038/s41598-019-50861-2

Cited by 31 publications

(22 citation statements)

References 79 publications

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“…The greatest difference in SSBs and DBSs for the emission profiles occurred at 400 eV where β + demonstrated a 55% integral increase in SSBs compared to electrons, and a 117% increase in DSBs. These results are consistent with our previous study demonstrating the use of 89 Zr and 64 Cu for dose enhancement in nuclear medicine imaging compared to β − therapeutic isotopes such as 67 Cu, by virtue of their higher ionization properties 13 . Another in vivo study demonstrated that both 64 Cu (with 38.5% β − ) and 67 Cu (with 100% β − ) were an effective targeted β − RNT for subcutaneous human colon carcinoma carried in hamster thighs when radiolabeled with a mouse anti-human colorectal cancer 14 .…”

Section: Mainsupporting

confidence: 93%

Overlooked potential of positrons in cancer therapy

Hioki

Gholami

McKelvey

et al. 2021

Sci Rep

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Positron (β+) emitting radionuclides have been used for positron emission tomography (PET) imaging in diagnostic medicine since its development in the 1950s. Development of a fluorinated glucose analog, fluorodeoxyglucose, labelled with a β+ emitter fluorine-18 (18F-FDG), made it possible to image cellular targets with high glycolytic metabolism. These targets include cancer cells based on increased aerobic metabolism due to the Warburg effect, and thus, 18F-FDG is a staple in nuclear medicine clinics globally. However, due to its attention in the diagnostic setting, the therapeutic potential of β+ emitters have been overlooked in cancer medicine. Here we show the first in vitro evidence of β+ emitter cytotoxicity on prostate cancer cell line LNCaP C4-2B when treated with 20 Gy of 18F. Monte Carlo simulation revealed thermalized positrons (sub-keV) traversing DNA can be lethal due to highly localized energy deposition during the thermalization and annihilation processes. The computed single and double strand breakages were ~ 55% and 117% respectively, when compared to electrons at 400 eV. Our in vitro and in silico data imply an unexplored therapeutic potential for β+ emitters. These results may also have implications for emerging cancer theranostic strategies, where β+ emitting radionuclides could be utilized as a therapeutic as well as a diagnostic agent once the challenges in radiation safety and protection after patient administration of a radioactive compound are overcome.

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Section: Mainsupporting

confidence: 93%

Overlooked potential of positrons in cancer therapy

Hioki

Gholami

McKelvey

et al. 2021

Sci Rep

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“…They demonstrated not only radio-enhancement for internal RT by use of NPs, but also the strongest interaction with 20 nm inter-NP distance. 77 One of the most crucial aims of the production of nanocarriers as drug carriers is to develop safer and more effective therapeutic and diagnostic modalities. 78 Imaging can be successfully used for the evaluation of biodistribution and pharmacokinetics of nanomedicine-based drug delivery systems.…”

Section: Drug Delivery Systemsmentioning

confidence: 99%

Targeted Alpha Therapy and Nanocarrier Approach

Silindir-Gunay

Karpuz

Özer

2020

Cancer Biotherapy and Radiopharmaceuticals

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The rates of cancer incidence and mortality are increasing day by day. Although several conventional methods including surgery, chemotherapy, and radiotherapy (RT) exist for cancer treatment, they are insufficient in the eradication of all tumor tissues and have some side-effects such as narrow therapeutic index and serious sideeffects to healthy tissues. Moreover, it may probably recur in time due to the survival and spreading of cancerous cells or any possible metastases. Targeted radionuclide therapy is a promising alternative. a particles are ideal for localized cell killing because of their high linear energy transfer and short ranges. However, upon emission of a particles, the daughter nuclides induce a recoil energy to lead decoupling from any chemical bond that may accumulate in normal tissues. Targeted a therapy can also be performed by targeted delivery systems apart from mAb, mAb fragments, peptides, and small molecules for selective tumor therapy. Targeted drug delivery systems have been developed to overcome the limitations of a therapy. Moreover, drug delivery systems are one of the most searched applications in cancer imaging and/or treatment due to their targeting ability to tumor or biocompatibility properties. The aim of this article is to summarize tumor therapy applications, targeted a RT approach, and to review the role of drug delivery systems in the delivery of a particles for cancer therapy and some instances of targeted a-emitting drug delivery systems from the literature.

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“…Thus, HIR-FH can also potentially offer a unique platform for targeted and selective internal radionuclide therapy, 78 while HIR-FH or in general any HIR radiometal-SPION can serve as metal-based radio-enhancer as we have recently reported. 79 With its simple chemical synthesis procedure, HIR can be potentially utilized in clinical settings without the possible complications of a chelate-based chemistry. 33-35,46,50 (5) While there currently exist both single- 72 or dual-modality 66 nanoparticle platforms, the chelatefree HIR method discussed in this work is also conducive to the development of multimodal imaging probes, allowing for new areas of research.…”

Section: Significance Of Chelate-free Hir Radiolabelingmentioning

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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Radio-enhancement effects by radiolabeled nanoparticles

Cited by 31 publications

References 79 publications

Overlooked potential of positrons in cancer therapy

Overlooked potential of positrons in cancer therapy

Targeted Alpha Therapy and Nanocarrier Approach

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

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