scholarly journals Biological behavior of a new 68Ga-labelled glucose derivative as a potential agent for tumor imaging

2021 ◽  
Vol 2058 (1) ◽  
pp. 012037
Author(s):  
V K Tishchenko ◽  
V M Petriev ◽  
K A Kuzenkova ◽  
I N Zavestovskaya ◽  
P V Shegai ◽  
...  
Keyword(s):  
Tumor Imaging ◽  
Biological Behavior ◽  
Tumor Uptake ◽  
Aseptic Inflammation ◽  
Promising Alternative ◽  
Tumor Bearing ◽  
Pet Tracer ◽  
Biodistribution Studies ◽  
Positron Emitter ◽  
Glucose Derivative

Abstract Glucose analogs and derivatives labeled with positron emitter 68Ga are considered to be a promising alternative to widely used radiotracer 18F-FDG for tumor PET imaging. In this study a biodistribution of a new glucose derivative labeled with 68Ga (68Ga-NODA-thioglucose) was investigated. All biodistribution studies were carried out in Balb/c mice with experimental model of tumor or aseptic inflammation. The tumor uptake of 68Ga-NODA-TG decreased throughout the study from 3.00±0.08 % ID/g to 1.06±0.04 %ID/g. The peak amount of 68Ga-NODA-TG in muscle with inflammation reached 4.33±0.12 % ID/g, decreasing to 0.23±0.08 % ID/g. In other organs and tissues the biodistribution of 68Ga-NODA-TG was similar in tumor-bearing mice and mice with aseptic inflammation. In conclusion, the obtained results suggest that 68Ga-NODA-TG has the potential for clinical application as a PET tracer.

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.

Effect of lipophilicity on biological properties of 109Pd-porphyrin complexes: a preliminary investigation

2012 ◽  
Vol 16 (01) ◽  
pp. 64-71 ◽  
Author(s):  
Sudipta Chakraborty ◽  
Tapas Das ◽  
Haladhar D. Sarma ◽  
Sharmila Banerjee
Keyword(s):  
Specific Activity ◽  
Tumor Therapy ◽  
Preliminary Investigation ◽  
Biological Properties ◽  
Biological Behavior ◽  
High Yield ◽  
Tumor Uptake ◽  
Background Ratio ◽  
Biodistribution Studies ◽  
Pd Complexes

The present study is designed to investigate the effect of lipophilicity of 109Pd-porphyrin complexes on their biological properties which were evaluated in tumor-bearing animal model. The insight obtained could be utilized to develop other radiometalated porphyrin complexes with optimum tumor uptake and tumor to background ratio as potential agents for targeted tumor therapy. 109Pd was produced by thermal neutron bombardment on enriched (in 109Pd) metallic palladium target at a flux of 3 × 1013 n/cm2.s for 3 d. 109Pd complexes of three different porphyrin derivatives, namely, 5,10,15,20-tetrakis[3,4- bis(carboxymethyleneoxy)phenyl]porphyrin(I), 5,10,15,20-tetrakis[3,4-bis(carboethoxymethyleneoxy)phenyl]porphyrin(II) and 5,10,15,20-tetrakis[4-carboxymethyleneoxyphenyl]porphyrin(III), which differ in their peripheral substituents, were synthesized. The biological behavior of the complexes was studied in Swiss mice bearing fibrosarcoma tumors. 109Pd was produced with a specific activity of ~1.85 GBq/mg (50 mCi/mg) and radionuclidic purity of 100%. All the 109Pd complexes were obtained in high yield (>97%) and they exhibited satisfactory in vitro stability at room temperature. The lipophilicity of the complexes follows the order 109Pd-II ≫ 109Pd-III > 109Pd-I. Biodistribution studies revealed that the most lipophilic 109Pd-II complex exhibited highest initial tumor uptake but poor tumor/liver ratio, while 109Pd-III complex exhibited the best tumor/liver ratio with reasonably good tumor accumulation. The lipophilicity of 109Pd-porphyrin complexes was found to have considerable effect on their biological characteristics and radiometal-porphyrin complexes with optimum tumor uptake and adequately high tumor to background ratio could be synthesized by optimization of the lipophilicity through proper selection of peripheral substituents.

Bifunctional HPPH-N2S2-99mTc conjugates as tumor imaging agents: synthesis and biodistribution studies

2003 ◽  
Vol 07 (07) ◽  
pp. 500-507 ◽  
Author(s):  
Bing Ma ◽  
Guolin Li ◽  
Peter Kanter ◽  
Dominick Lamonica ◽  
Zachary Grossman ◽  
...  
Keyword(s):  
Half Life ◽  
Tumor Imaging ◽  
Post Injection ◽  
Tumor Uptake ◽  
In Vivo Biodistribution ◽  
Structure Activity ◽  
Biodistribution Studies ◽  
Activity Screening ◽  
Pyropheophorbide A

Pyropheophorbide-a and the corresponding 3-(1'-hexyloxyethyl)-3-devinyl derivative ( HPPH ), the tumor-avid photosensitizers were conjugated with mono- or di-bisaminoethanethiols ( N 2 S 2 ligand). The in vivo biodistribution study of the related 99m Tc complexes was performed in F-344 rats bearing Ward colon tumors at 4 h and 24 h post injection. These data show that the complexes are stable and among four tracers, HPPH di-99 m Tc N 2 S 2 conjugate reaches the highest tumor uptake (%ID/g). The larger tumors reach higher concentrations of the tracer. However, the short 6 h half life of 99 m Tc is incompatible with the 24 h imaging time, suggesting that the use of a longer-lived isotope such as 111 In could still provide a useful scanning agent, or that further structure-activity screening could yield an HPPH analog with more appropriate pharmacokinetics for tumor imaging with 99 m Tc .

scholarly journals Competitive blocking of salivary gland [18F]DCFPyL uptake via localized, retrograde ductal injection of non-radioactive DCFPyL: a preclinical study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jyoti Roy ◽  
Blake M. Warner ◽  
Falguni Basuli ◽  
Xiang Zhang ◽  
Changyu Zheng ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Dose Range ◽  
Systemic Circulation ◽  
Preclinical Study ◽  
Dose Finding ◽  
Tumor Uptake ◽  
Tumor Bearing ◽  
Biodistribution Studies ◽  
Novel Approach ◽  
Dose Levels

Abstract Background PSMA-targeted radionuclide therapy (TRT) is a promising treatment for prostate cancer (PCa), but dose-limiting xerostomia can severely limit its clinical adaptation, especially when using alpha-emitting radionuclides. With [18F]DCFPyL as a surrogate for PSMA-TRT, we report a novel method to selectively reduce salivary gland (SG) uptake of systemically administered [18F]DCFPyL by immediate prior infusion of non-radioactive standard of [18F]DCFPyL (DCFPyL) directly into the SG via retrograde cannulation. Methods A dose-finding cohort using athymic nude mice demonstrated proof of principle that SG uptake can be selectively blocked by DCFPyL administered either locally via cannulation (CAN group) or systemically (SYS group). The experiments were repeated in a validation cohort of 22RV1 tumor-bearing mice. Submandibular glands (SMG) of CAN mice were locally blocked with either saline or DCFPyL (dose range: 0.01× to 1000× molar equivalent of the radioactive [18F]DCFPyL dose). The radioactive dose of [18F]DCFPyL was administered systemically 10 min later and the mice euthanized after 1 h for biodistribution studies. Toxicity studies were done at up to 1000× dose. Results In the dose-finding cohort, the SYS group showed a dose-dependent 12–40% decrease in both the SMG T/B and the kidney (tumor surrogate). Mild blocking was observed at 0.01× , with maximal blocking reached at 1× with no additional blocking up to 1000× . In the CAN group, blocking at the 0.1× and 1× dose levels resulted in a similar 42–53% decrease, but without the corresponding decrease in kidney uptake as seen in the SYS group. Some evidence of “leakage” of DCFPyL from the salivary gland into the systemic circulation was observed. However, experiments in 22RV1 tumor-bearing mice at the 0.1× and 1× dose levels confirm that, at the appropriate blocking dose, SG uptake of [18F]DCFPyL can be selectively reduced without affecting tumor uptake and with no toxicity. Conclusion Our results suggest that direct retrograde instillation of DCFPyL into the SG could predictably and selectively decrease salivary uptake of systemically administered [18F]DCFPyL without altering tumor uptake, if given at the appropriate dose. This novel approach is easily translatable to clinical practice and has the potential to mitigate xerostomia, without compromising the therapeutic efficacy of the PSMA-TRT.

scholarly journals Competitive Blocking of Salivary Gland [18F]DCFPyL Uptake via Localized, Retrograde Ductal Injection of Non-radioactive DCFPyL: A Preclinical Study

2021 ◽  
Author(s):  
Jyoti Roy ◽  
Blake M Warner ◽  
Falguni Basuli ◽  
Xiang Zhang ◽  
Changyu Zheng ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Dose Range ◽  
Systemic Circulation ◽  
Preclinical Study ◽  
Dose Finding ◽  
Tumor Uptake ◽  
Tumor Bearing ◽  
Biodistribution Studies ◽  
Novel Approach ◽  
Dose Levels

Abstract BACKGROUNDPSMA-targeted radionuclide therapy (TRT) is a promising treatment for prostate cancer (PCa) but dose-limiting xerostomia can severely limit its clinical adaptation, especially when using alpha-emitting radionuclides. With [18F]DCFPyL as a surrogate for PSMA-TRT, we report a novel method to selectively reduce salivary gland (SG) uptake of systemically administered [18F]DCFPyL by immediate prior infusion of non-radioactive standard of [18F]DCFPyL (DCFPyL) directly into the SG via retrograde cannulation. METHODSA dose-finding cohort using athymic nude mice demonstrated proof-of-principle that SG uptake can be selectively blocked by DCFPyL administered either locally via cannulation (CAN group) or systemically (SYS group). The experiments were repeated in a validation cohort of 22RV1 tumor-bearing mice. Submandibular glands (SMG) of CAN mice were locally blocked with either saline or DCFPyL (dose range: 0.01x to 1000x molar equivalent of the radioactive [18F]DCFPyL dose). The radioactive dose of [18F]DCFPyL was administered systemically 10 minutes later and the mice euthanized after 1 hour for biodistribution studies. Toxicity studies were done at up to 1000x dose. RESULTSIn the dose-finding cohort, the SYS group showed a dose-dependent 12-40% decrease in both the SMG T:B and the kidney (tumor surrogate). Mild blocking was observed at 0.01x, with maximal blocking reached at 1x with no additional blocking up to 1000x. In the CAN group, blocking at the 0.1x and 1x dose levels resulted in a similar 42-53% decrease, but without the corresponding decrease in kidney uptake as seen in the SYS group. Some evidence of “leakage” of DCFPyL from the salivary gland into the systemic circulation was observed. However, experiments in 22RV1 tumor-bearing mice at the 0.1x and 1x dose levels confirm that, at the appropriate blocking dose, SG uptake of [18F]DCFPyL can be selectively reduced without affecting tumor uptake and with no toxicity.CONCLUSIONOur results suggest that direct retrograde instillation of DCFPyL into the SG could predictably and selectively decrease salivary uptake of systemically administered [18F]DCFPyL without altering tumor uptake, if given at the appropriate dose. This novel approach is easily translatable to clinical practice and has the potential to mitigate xerostomia, without compromising the therapeutic efficacy of the PSMA-TRT.

scholarly journals Development of68Ga-Glycopeptide as an Imaging Probe for Tumor Angiogenesis

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Ning Tsao ◽  
Chau-Hui Wang ◽  
Li-Jane Her ◽  
Kai-Yuan Tzen ◽  
Jing-Yi Chen ◽  
...  
Keyword(s):  
New Zealand ◽  
Tumor Angiogenesis ◽  
Half Life ◽  
Tumor Imaging ◽  
In Vivo Studies ◽  
Blood Clearance ◽  
Tumor Uptake ◽  
Tumor Bearing ◽  
New Zealand White Rabbits

Objective. This study was aimed to study tissue distribution and tumor imaging potential of68Ga-glycopeptide (GP) in tumor-bearing rodents by PET.Methods. GP was synthesized by conjugating glutamate peptide and chitosan. GP was labeled with68Ga chloride for in vitro and in vivo studies. Computer outlined region of interest (counts per pixel) of the tumor and muscle (at the symmetric site) was used to determine tumor-to-muscle count density ratios. To ascertain the feasibility of68Ga-GP in tumor imaging in large animals, PET/CT imaging of68Ga-GP and18F-FDG were conducted in New Zealand white rabbits bearing VX2 tumors. Standard uptake value of tumors were determined by PET up to 45 min. To determine blood clearance and half-life of68Ga-GP, blood samples were collected from 10 seconds to 20 min.Results. Radiochemical purity of68Ga-GP determined by instant thin-layer chromatography was >95%. Tumor uptake values (SUV) for68Ga-GP and18F-FDG in New Zealand white rabbits bearing VX2 tumors were 3.25 versus 7.04. PET images in tumor-bearing rats and rabbits confirmed that68Ga-GP could assess tumor uptake. From blood clearance curve, the half-life of68Ga-GP was 1.84 hr.ConclusionOur data indicate that it is feasible to use68Ga-GP to assess tumor angiogenesis.

Copper-64 labeled sulfophthalocyanines for positron emission tomography (PET) imaging in tumor-bearing rats

2008 ◽  
Vol 12 (01) ◽  
pp. 49-53 ◽  
Author(s):  
Anton Soucy-Faulkner ◽  
Jacques A. Rousseau ◽  
Réjean Langlois ◽  
Véronique Berard ◽  
Roger Lecomte ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Photodynamic Therapy ◽  
Emission Tomography ◽  
Tumor Uptake ◽  
Tissue Samples ◽  
Metal Free ◽  
Tumor Bearing ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Tumor Selectivity

Sulfonated metallophthalocyanines ( PcS ) are second generation photosensitizers for photodynamic therapy (PDT) of cancer. Metal-free H 2 PcS are readily labeled with 64 Cu ++ to yield a mixture of sulfonated [64 Cu ] CuPcS suitable for biodistribution studies in tumor-bearing rats by positron emission tomography (PET). Most of the 64 Cu activity was sequestrated within the kidneys (20%ID/g) and liver (12%ID/g) while tumor uptake values remained low (0.2%ID/g). Dissection and counting of individual tissue samples after the 24 h scan confirmed the uptake values derived from the PET images. The procedure can be applied to series of novel PcS to evaluate structure-tumor selectivity relationships as a parameter to select potential agents for photodynamic therapy.

Evaluation studies of technetium-99m-porphyrin (T3,4BCPP) for tumor imaging

2001 ◽  
Vol 05 (12) ◽  
pp. 824-828 ◽  
Author(s):  
MURUGESAN SUBBARAYAN ◽  
S. J. SHETTY ◽  
T. S. SRIVASTAVA ◽  
O. P. D. NORONHA ◽  
A. M. SAMUEL
Keyword(s):  
Mammary Tumor ◽  
Gamma Camera ◽  
Tumor Imaging ◽  
Evaluation Studies ◽  
Water Soluble ◽  
Tumor Bearing ◽  
Biodistribution Studies ◽  
Distribution Studies ◽  
Water Soluble Porphyrin

A water-soluble porphyrin, 5,10,15,20-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl] porphyrin (T3,4BCPP), was successfully labeled with 99 m Tc and biodistribution studies were performed in Wistar rats. Scintiimaging and in vivo distribution studies were also carried out in C 6-gliomas and mammary tumor-bearing animals using a gamma camera. Tumor-to-muscle (T/M) ratios were calculated and compared with those obtained with the known tumor-seeking radiopharmaceuticals 99 m Tc (V)- DMSA (DMSA = dimercaptosuccinic acid), 99 m Tc -citrate and 201 TlCl . In the case of C 6-gliomas, the ratios were 4.2, 2.2, 4.00 and 3.0; while in the case of C 3 H / J mammary tumor, the ratios were 9.4, 8.8, 8.1 and 8.5 for T3,4BCPP, 99 m Tc ( V )- DMSA , 99 m Tc -citrate and 201 TlCl , respectively. Similar studies were carried out in N-methyl-N-nitrosourea ( NMU )-induced mammary tumor animals and the T/M ratios obtained were 5.9, 2.0, 5.3 and 3.3 for T3,4BCPP, 99 m Tc ( V )- DMSA , 99 m Tc -citrate and 201 TlCl , respectively. The radiolabeled photosensitizer could perhaps be used to detect cancer non-invasively and could even prove useful in monitoring the progression/regression of tumors before, during, and after chemotherapy, radiation therapy or photodynamic therapy (PDT).

Evaluation of New 99mTc(CO)3 + Radiolabeled Glycylglycine In Vivo

2019 ◽  
Vol 19 (11) ◽  
pp. 1382-1387
Author(s):  
Ahmet M. Şenışık ◽  
Çiğdem İçhedef ◽  
Ayfer Y. Kılçar ◽  
Eser Uçar ◽  
Kadir Arı ◽  
...  
Keyword(s):  
High Performance ◽  
The Body ◽  
Biological Behavior ◽  
In Vivo Evaluation ◽  
Radiolabeled Peptides ◽  
Tumor Bearing ◽  
Biodistribution Data ◽  
Good Accordance ◽  
Rapid Clearance

Background: Peptide-based agents are used in molecular imaging due to their unique properties, such as rapid clearance from the circulation, high affinity and target selectivity. Many of the radiolabeled peptides have been clinically experienced with diagnostic accuracy. The aim of this study was to investigate in vivo biological behavior of [99mTc(CO)3(H2O)3]+ radiolabeled glycylglycine (GlyGly). Methods: Glycylglycine was radiolabeled with a high radiolabeling yield of 94.69±2%, and quality control of the radiolabeling process was performed by thin layer radiochromatography (TLRC) and High-Performance Liquid Radiochromatography (HPLRC). Lipophilicity study for radiolabeled complex (99mTc(CO)3-Gly-Gly) was carried out using solvent extraction. The in vivo evaluation was performed by both biodistribution and SPECT imaging. Results: The high radiolabelling yield of 99mTc(CO)3-GlyGly was obtained and verified by TLRC and HPLRC as well. According to the in vivo results, SPECT images and biodistribution data are in good accordance. The excretion route from the body was both hepatobiliary and renal. Conclusion: This study shows that 99mTc(CO)3-GlyGly has the potential to be used as a peptide-based imaging agent. Further studies, 99mTc(CO)3-GlyGly can be performed on tumor-bearing animals.

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