scholarly journals Tissue distribution and tumor uptake of folate receptor–targeted epothilone folate conjugate, BMS-753493, in CD2F1 mice after systemic administration

2016 ◽  
Vol 6 (5) ◽  
pp. 460-467 ◽  
Author(s):  
Hong Shen ◽  
Lifei Wang ◽  
Weiqi Chen ◽  
Krista Menard ◽  
Yang Hong ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Folate Receptor ◽  
Systemic Administration ◽  
Tumor Uptake ◽  
Folate Conjugate

scholarly journals Therapeutic Potential of 47Sc in Comparison to 177Lu and 90Y: Preclinical Investigations

Pharmaceutics ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 424 ◽  
Author(s):  
Klaudia Siwowska ◽  
Patrycja Guzik ◽  
Katharina A. Domnanich ◽  
Josep M. Monné Rodríguez ◽  
Peter Bernhardt ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Therapeutic Potential ◽  
Folate Receptor ◽  
Tumor Growth Inhibition ◽  
Therapeutic Effects ◽  
Targeted Radionuclide Therapy ◽  
Decay Properties ◽  
Therapeutic Properties ◽  
Folate Conjugate

Targeted radionuclide therapy with 177Lu- and 90Y-labeled radioconjugates is a clinically-established treatment modality for metastasized cancer. 47Sc is a therapeutic radionuclide that decays with a half-life of 3.35 days and emits medium-energy β−-particles. In this study, 47Sc was investigated, in combination with a DOTA-folate conjugate, and compared to the therapeutic properties of 177Lu-folate and 90Y-folate, respectively. In vitro, 47Sc-folate demonstrated effective reduction of folate receptor-positive ovarian tumor cell viability similar to 177Lu-folate, but 90Y-folate was more potent at equal activities due to the higher energy of emitted β−-particles. Comparable tumor growth inhibition was observed in mice that obtained the same estimated absorbed tumor dose (~21 Gy) when treated with 47Sc-folate (12.5 MBq), 177Lu-folate (10 MBq), and 90Y-folate (5 MBq), respectively. The treatment resulted in increased median survival of 39, 43, and 41 days, respectively, as compared to 26 days in untreated controls. There were no statistically significant differences among the therapeutic effects observed in treated groups. Histological assessment revealed no severe side effects two weeks after application of the radiofolates, even at double the activity used for therapy. Based on the decay properties and our results, 47Sc is likely to be comparable to 177Lu when employed for targeted radionuclide therapy. It may, therefore, have potential for clinical translation and be of particular interest in tandem with 44Sc or 43Sc as a diagnostic match, enabling the realization of radiotheragnostics in future.

scholarly journals Synthesis and evaluation of radiolabeled, folic acid-PEG conjugated, amino silane coated magnetic nanoparticles in tumor bearing Balb/C mice

Nukleonika ◽  
2015 ◽  
Vol 60 (3) ◽  
pp. 497-502 ◽  
Author(s):  
Javad Razjouyan ◽  
Hamidreza Zolata ◽  
Omid Khayat ◽  
Fereidoun Nowshiravan ◽  
Nami Shadanpour ◽  
...  
Keyword(s):  
Folic Acid ◽  
Folate Receptor ◽  
Superparamagnetic Iron Oxide ◽  
Fibroblast Cell ◽  
Mouse Fibroblast ◽  
Tumor Uptake ◽  
Mri Imaging ◽  
Tumor Bearing ◽  
Biodistribution Studies

Abstract To design a potent agent for positron emission tomography/magnetic resonance imaging (PET/MRI) imaging and targeted magnetic hyperthermia-radioisotope cancer therapy radiolabeled surface modified superparamagnetic iron oxide nanoparticles (SPIONs) were used as nanocarriers. Folic acid was conjugated for increasing selective cellular binding and internalization through receptor-mediated endocytosis. SPIONs were synthesized by the thermal decomposition of tris (acetylacetonato) iron (III) to achieve narrow and uniform nanoparticles. To increase the biocompatibility of SPIONs, they were coated with (3-aminopropyl) triethoxysilane (APTES), and then conjugated with synthesized folic acid-polyethylene glycol (FA-PEG) through amine group of (3-aminopropyl) triethoxysilane. Finally, the particles were labeled with 64Cu (t1/2 = 12.7 h) using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono (N-hydroxy succinimide ester) DOTA-NHS chelator. After the characterization of SPIONs, their cellular internalization was evaluated in folate receptor (FR) overexpressing KB (established from a HeLa cell contamination) and mouse fibroblast cell (MFB) lines. Eventually, active and passive targeting effects of complex were assessed in KB tumor-bearing Balb/C mice through biodistribution studies. Synthesized bare SPIONs had low toxicity effect on healthy cells, but surface modification increased their biocompatibility. Moreover, KB cells viability was reduced when using folate conjugated SPIONs due to FR-mediated endocytosis, while having little effect on healthy cells (MFB). Moreover, this radiotracer had tolerable in vivo characteristics and tumor uptake. In the receptor blocked case, tumor uptake was decreased, indicating FR-specific uptake in tumor tissue while enhanced permeability and retention effect was major mechanism for tumor uptake.

Synthesis, tissue distribution and tumor uptake of [99Tc]tetrasulfophthalocyanine

1983 ◽  
Vol 34 (3) ◽  
pp. 571-579 ◽  
Author(s):  
Jacques Rousseau ◽  
Dieter Autenrieth ◽  
Johan E. Van Lier
Keyword(s):  
Tissue Distribution ◽  
Tumor Uptake

Dynamic Contrast-Enhanced Folate-Receptor-Targeted MR Imaging Using a Gd-loaded PEG-Dendrimer–Folate Conjugate in a Mouse Xenograft Tumor Model

2009 ◽  
Vol 12 (2) ◽  
pp. 145-154 ◽  
Author(s):  
Wei-Tsung Chen ◽  
Dhakshanamurthy Thirumalai ◽  
Tiffany Ting-Fang Shih ◽  
Ran-Chou Chen ◽  
Shin-Yang Tu ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Folate Receptor ◽  
Tumor Model ◽  
Xenograft Tumor ◽  
Mouse Xenograft ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced ◽  
Xenograft Tumor Model ◽  
Folate Conjugate

Tissue distribution of enrofloxacin after intramammary or simulated systemic administration in isolated perfused sheep udders

2012 ◽  
Vol 73 (11) ◽  
pp. 1728-1734 ◽  
Author(s):  
Cristina López Cadenas ◽  
Nélida Fernández Martínez ◽  
Matilde Sierra Vega ◽  
Maria J. Diez Liébana ◽  
Jose M. Gonzalo Orden ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Systemic Administration

Folate-receptor-targeted delivery of docetaxel nanoparticles prepared by PLGA–PEG–folate conjugate

2008 ◽  
Vol 16 (5) ◽  
pp. 415-423 ◽  
Author(s):  
Farnaz Esmaeili ◽  
Mohammad Hossein Ghahremani ◽  
Seyed Nasser Ostad ◽  
Fatemeh Atyabi ◽  
Mohammad Seyedabadi ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Folate Receptor ◽  
Folate Conjugate

Folate Receptor Saturation, Recycling, and Release Kinetics in Activated Macrophages

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4655-4655
Author(s):  
Bindu Varghese ◽  
Erina Vlashi ◽  
Philip S. Low
Keyword(s):  
Folic Acid ◽  
Folate Receptor ◽  
Release Kinetics ◽  
Water Soluble ◽  
Imaging Agents ◽  
Activated Macrophages ◽  
Binding Characteristics ◽  
Folate Conjugate ◽  
Made In

Abstract Activated macrophages over-express a receptor for the vitamin, folic acid. Conjugation of folic acid to low molecular weight drugs, genes, liposomes, nanoparticles, and imaging agents does not significantly compromise the vitamin’s affinity for its receptor, thus facilitating both therapeutic and imaging agents to be targeted as folate conjugates to activated macrophages. In these studies the in vivo kinetics and binding characteristics of the folate receptor on macrophages has been characterized with the objective of optimizing targeted drug delivery. Our results show that saturation of the receptor in inflamed tissues can be reached at a dose of 100 nmol/kg. Furthermore, the rapid recycling characteristics of the receptor (every 10–20 minutes) suggests that frequent dosing will allow for maximal uptake of folate conjugates by activated macrophages accumulated in inflamed tissues. Finally, the short circulation half-life (30 minutes) of the water-soluble folate conjugate used in this study minimizes the possibility of nonspecific uptake by receptor-negative tissues. The kinetic observations made in this study can be utilized to optimize the therapeutic efficacy and imaging agent delivery of folate conjugates to activated macrophages in vivo.

scholarly journals Imaging of Folate Receptor Expressing Macrophages in the Rat Groove Model of Osteoarthritis: Using a New DOTA-Folate Conjugate

Cartilage ◽  
2017 ◽  
Vol 9 (2) ◽  
pp. 183-191 ◽  
Author(s):  
Huub M. de Visser ◽  
Nicoline M. Korthagen ◽  
Cristina Müller ◽  
Ruud M. Ramakers ◽  
Gerard C. Krijger ◽  
...  
Keyword(s):  
Computed Tomography ◽  
High Fat Diet ◽  
Folate Receptor ◽  
Cartilage Damage ◽  
Receptor Expression ◽  
Emission Computed Tomography ◽  
Albumin Binding ◽  
High Fat ◽  
Folate Conjugate

Objective To evaluate the presence and localization of folate receptor expressing macrophages in the rat groove model of osteoarthritis and determine the suitability of a new folate conjugate with albumin-binding entity (cm09) for in vivo SPECT (single-photon emission computed tomography) analysis. Design In male Wistar rats, local cartilage damage was induced in addition to a standard ( n = 10) or high-fat diet ( n = 6). After 12 weeks, 111In labeled folate conjugates were administered, and SPECT/CT (computed tomography) imaging was performed after 24 hours. Subsequently, osteoarthritis severity and folate receptor expression were assessed using (immuno)-histological sections. Results In vivo SPECT/CT imaging of the new folate conjugate (cm09) was as useful as a folate conjugate without albumin-binding entity in the groove model of osteoarthritis with less renal accumulation. Induction of cartilage damage on a standard diet resulted in no effect on the amount of folate receptor expressing macrophages compared with the contralateral sham operated joints. In contrast, inducing cartilage damage in the high-fat diet group resulted in 28.4% increase of folate receptor expression as compared with the nondamaged control joints. Folate receptor expressing cells were predominantly present in the synovial lining and in subchondral bone as confirmed by immunohistochemistry. Conclusions Folate receptor expression, and thus macrophage activation, can clearly be demonstrated in vivo, in small animal models of osteoarthritis using the new 111In-folate conjugate with specific binding to the folate receptor. Increased macrophage activity only plays a role in the groove model of osteoarthritis when applied in a high-fat diet induced dysmetabolic condition, which is in line with the higher inflammatory state of that specific model.

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