Development of technetium-99m labeled ultrafine gold nanobioconjugates for targeted imaging of folate receptor positive cancers

Kumar, Dheeraj; Sakhare, Navin; Das, Soumen; Kale, Pooja; Mathur, Anupam; Mirapurkar, Shubhangi; Muralidharan, Sheela; Chaudhari, Pradip; Mohanty, Bhabani; Ballal, Anand; Patro, P.K.

doi:10.1016/j.nucmedbio.2020.11.001

Cited by 8 publications

(3 citation statements)

References 33 publications

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“…Looking beyond 99m Tc-sestamibi, the only radiotracer routinely used for clinical MBI preferentially localized in mitochondria of malignant cancer cells but also localized in varying levels within benign breast tissues, there are many new 99m Tc-labelled radiotracers are actively under development and are being designed to more specifically target and even differentiate breast cancers. 1,18 A PubMed search of "molecular breast imaging technetium-99 m" manuscripts published since 2020 reveals on-going in vitro, pre-clinical, and even some initial human trials using 99m Tc-labelled antibodies and affibodies, gold and silicon nanoparticles, and peptides and proteins to visualize, for example, general breast tumors, [19][20][21] human epidermal growth factor receptor 2 and folate receptor expression in breast tumors, [22][23][24][25][26] epithelial cell adhesion molecules expression in triple negative breast cancers, 27 and even angiogenesis via α v β 3 -integrin receptor targets. 28,29 Thanks to improvements in MBI system sensitivity and resolution, largely due to the optimization of the detector and collimator design, 18 MBI with proper quantification techniques may be uniquely positioned to become an alternative modality to whole-body SPECT/CT to image these new 99m Tc-labelled tracers.…”

Section: Discussionmentioning

confidence: 99%

Monte Carlo‐derived ^99mTc uptake quantification with commercial planar MBI: Tumor and breast activity concentrations

López

Kappadath

2023

Medical Physics

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Background Current molecular breast imaging (MBI) images are limited to qualitative evaluation, not absolute measurement, of 99mTc uptake in benign and malignant breast tissues. Purpose This work assesses the accuracy of previously‐published and newly‐proposed tumor and normal breast tissue 99mTc uptake MBI measurements using simulations of a commercial dual‐headed planar MBI system under typical clinical and acquisition protocols. Methods Quantification techniques were tested in over 4000 simulated acquisitions of spherical and ellipsoid tumors with clinically relevant uptake conditions using a validated Monte Carlo application of the GE Discovery NM750b system. The evaluated techniques consisted of four tumor total activity methodologies (two single‐detector‐based and two geometric‐mean‐based), two tumor MBI volume methodologies (diameter‐based and ROI‐based), and two normal tissue activity concentration methodologies (single‐detector‐based and geometric‐mean‐based). The most accurate of these techniques were then used to estimate tumor activity concentrations and tumor to normal tissue relative activity concentrations (RC). Results Single‐detector techniques for tumor total activity quantification achieved mean (standard deviation) relative errors of 0.2% (4.3%) and 1.6% (4.4%) when using the near and far detector images, respectively and were more accurate and precise than the measured 8.1% (5.8%) errors of a previously published geometric‐mean technique. Using these activity estimates and the true tumor volumes resulted in tumor activity concentration and RC errors within 10% of simulated values. The precision of tumor activity concentration and RC when using only MBI measurements were largely driven by the errors in estimating tumor MBI volume using planar images (± 30% inter‐quartile range). Conclusions Planar MBI images were shown to accurately and reliably be used to estimate tumor total activities and normal tissue activity concentrations in this simulation study. However, volumetric tumor uptake measurements (i.e., absolute and relative concentrations) are limited by inaccuracies in MBI volume estimation using two‐dimensional images, highlighting the need for either tomographic MBI acquisitions or anatomical volume estimates for accurate three‐dimensional tumor uptake estimates.

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Section: Discussionmentioning

confidence: 99%

Monte Carlo‐derived ^99mTc uptake quantification with commercial planar MBI: Tumor and breast activity concentrations

López

Kappadath

2023

Medical Physics

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“…This solution allows the migration of free 99m TcO 4 - to the front of the strips (RF: 1.0 for 99m TcO 4 − ), while NaCl 0.9% as the mobile phase allows the migration to the front of both free 99m TcO 4 - and 99m Tc-EDDA/tricine (RF: 1.0 for 99m TcO 4 - and 99m Tc-EDDA/tricine). In this way, it is possible to discriminate the percentage of the radioactive EDDA/tricine complex in solution [ 40 , 41 ].…”

Section: Radiolabelling Of Nps For Spect Imagingmentioning

confidence: 99%

Methods for Radiolabelling Nanoparticles: SPECT Use (Part 1)

et al. 2022

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The use of nanoparticles (NPs) is rapidly increasing in nuclear medicine for diagnostic and therapeutic purposes. Their wide use is due to their chemical–physical characteristics and possibility to deliver several molecules. NPs can be synthetised by organic and/or inorganic materials and they can have different size, shape, chemical composition, and char. These factors influence their biodistribution, clearance, and targeting ability in vivo. NPs can be designed to encapsulate inside the core or bind to the surface on several molecules, including radionuclides, for different clinical applications. Either diagnostic or therapeutic radioactive NPs can be synthetised, making a so-called theragnostic tool. To date, there are several methods for radiolabelling NPs that vary depending on both the physical and chemical properties of the NPs and on the isotope used. In this review, we analysed and compared different methods for radiolabelling NPs for single-photon emission computed tomography (SPECT) use.

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“…The accumulation in the liver and spleen of the drug was ascribed to the macrophages and other antigen-presenting cells of the mononuclear phagocyte system (MPS) 34 and kidney accumulation may be due to the surface functionalization of nanoparticles with folic acid, which is responsible for its affinity towards the kidneys. 35 However, after 12 h post-injection, accumulation in the kidney was markedly less. SPTX or PTX concentration was decreased after 12…”

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confidence: 98%

Optimization, Characterization and in vivo Evaluation of Paclitaxel-Loaded Folate-Conjugated Superparamagnetic Iron Oxide Nanoparticles

Gui¹,

Fan²,

Ning³

et al. 2021

IJN

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Background: Paclitaxel (PTX) has interesting anticancer activity. However, it is insoluble in water, which seriously hinders its use in clinical. Superparamagnetic iron oxide nanoparticles (SPIONs) are used as an ideal drug delivery system. Therefore, we proposed a folic acid (FA) targeting drug-loaded SPIONs to reduce its adverse reaction. Methods: To improve the hydrophilicity of PTX, the structure of PTX was modified by succinic anhydride to obtain 2ʹ-succinate paclitaxel (SPTX). FA conjugated Polyethylene glycol (PEG)/ polyethyleneimine (PEI)-SPIONs SPTX-loaded nanoparticles (SPTX@FA@PEG/PEI-SPIONs) were prepared by solvent volatilization and hydrogen bond adsorption, and the nano-formulation was optimized by response surface methodology (RSM). The characteristics, antitumor effect in vitro, pharmacokinetics, and biodistribution of SPTX@FA@PEG/PEI-SPIONs were evaluated. Results: SPTX was successfully loaded on the surface of FA@PEG/PEI-SPIONs. The formation of SPTX@FA@PEG/PEI-SPIONs was exhibited water-dispersive monodispersity with high stability by RSM, and dynamic light scattering (DLS) was 178.1±3.12 nm, particle size observed in the transmission electron microscope (TEM) was 13.01±1.10 nm, and the encapsulation efficiency (EE) and loading efficiency (LE) were 81.1±1.66% and 14.8±1.46%, respectively. It enhanced the stability in normal physiological condition, accelerated drug release at tumorous pH, and preferentially prolonged the circulation time. In vitro, the SPTX@FA@PEG/PEI-SPIONs significantly targeted to folate receptor (FR) positive cancers cell (HNE-1) via the receptor-ligand mediated pathway, resulting in effective cytotoxic activity. Pharmacokinetic results demonstrated that SPTX@FA@PEG/PEI-SPIONs (t 1/2 =3.41 h) had longer than free SPTX or PTX (t 1/2 =1.67 h) in rats in vivo. Tissue distribution studies showed that SPTX@FA@PEG/PEI-SPIONs were present at high levels in the liver and help in targeting the folate receptors present on the kidneys. Conclusion: These results suggest that SPTX@FA@PEG/PEI-SPIONs offer a highly promising approach to control drug release, improve drug pharmacokinetics and actively target the nasopharyngeal carcinoma.

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Development of technetium-99m labeled ultrafine gold nanobioconjugates for targeted imaging of folate receptor positive cancers

Cited by 8 publications

References 33 publications

Monte Carlo‐derived ^99mTc uptake quantification with commercial planar MBI: Tumor and breast activity concentrations

Monte Carlo‐derived ^99mTc uptake quantification with commercial planar MBI: Tumor and breast activity concentrations

Methods for Radiolabelling Nanoparticles: SPECT Use (Part 1)

Optimization, Characterization and in vivo Evaluation of Paclitaxel-Loaded Folate-Conjugated Superparamagnetic Iron Oxide Nanoparticles

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Development of technetium-99m labeled ultrafine gold nanobioconjugates for targeted imaging of folate receptor positive cancers

Cited by 8 publications

References 33 publications

Monte Carlo‐derived 99mTc uptake quantification with commercial planar MBI: Tumor and breast activity concentrations

Monte Carlo‐derived 99mTc uptake quantification with commercial planar MBI: Tumor and breast activity concentrations

Methods for Radiolabelling Nanoparticles: SPECT Use (Part 1)

Optimization, Characterization and in vivo Evaluation of Paclitaxel-Loaded Folate-Conjugated Superparamagnetic Iron Oxide Nanoparticles

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Product

Resources

About

Monte Carlo‐derived ^99mTc uptake quantification with commercial planar MBI: Tumor and breast activity concentrations

Monte Carlo‐derived ^99mTc uptake quantification with commercial planar MBI: Tumor and breast activity concentrations