Fatma Yurt Lambrecht

Synthesis and biological evaluation of radiolabeled photosensitizer linked bovine serum albumin nanoparticles as a tumor imaging agent

In this study, we reported on the synthesis and biological evaluation of radiolabeled fluorescent dye conjugated bovine serum albumin nanoparticles within the size range 190-210 nm. The bovine serum albumin nanoparticles (BSANPs) were prepared using a desolvation method, and chemical cross-linking was performed using gluteraldehyde. Furthermore, pheophorbide-a (PH-A) was loaded on the BSANPs. The results obtained from dynamic light scattering and electron microscopy have proved that nanoparticles are highly monodisperse and near-spherical shaped. The photo-physical properties of the PH-A-BSANPs were obtained using the spectrophotometric techniques. According to the results, PH-A and BSANPs show high non-covalent interaction. PH-A loaded nanoparticles were labeled with (99m)Tc and the radio-labeling efficiency was determined as 90 ± 1.2%. Biodistribution studies of (99m)Tc labeled PH-A-BSANPs and PH-A were carried out using female Albino Wistar rats, and (99m)Tc-PH-A-BSANPs showed a significantly higher uptake in the breast and uterus than (99m)Tc-PH-A. Cell culture study was carried out in MCF-7 cell line (human breast adenocarcinoma cell line). According to the cell culture studies, (99m)Tc-PH-A-BSANPs showed a higher uptake than (99m)Tc-PH-A. Moreover, PH-A-BSANPs demonstrated good photo-physical properties and BSANPs increased the uptake of PH-A on to the MCF-7 cell line. These results confirm that (99m)Tc labeled PH-A-BSANPs could be utilized for radioimaging.

Evaluation of 99mTc-labeled antibiotics for infection detection

One of the fields of research in nuclear medicine is the development of new radiopharmaceuticals for imaging infection and inflammation in humans. For this development, several antimicrobial peptides, antibiotics, antibiotic peptide and chemotactic peptides, etc., have been radiolabeled with different radionuclides (67Ga, 99mTc, 111In, 18F, 131I, etc.) and their imaging potentials studied. Actually, it is very important to distinguish between infection and inflammation. In this respect, radiolabeled antibiotics have advantages because many of the properties of the ideal infection-specific agent through antibiotics localizes in infection site. In this review, only 99mTc-labeled antibiotics are evaluated and discussed.

Design and synthesis of 99mTc-citro-folate for use as a tumor-targeted radiopharmaceutical

Folate conjugates exhibit high affinity for folate receptor (FR) positive cells and tissues, such as those in tumors, making them attractive candidates and of interest in diagnostic tumor imaging. The aim of study was to synthesize a novel radiopharmaceutical based folate conjugate, (99m)Tc-citro-folate, and to evaluate its efficiency as a targeted agent for imaging tumors that over express FR. TLC, HPLC (1)H NMR and LC-MS/MS methods were used to check and confirm the synthesized citro-folate. Citro-folate was labeled with Tc-99m with high labeling efficiency (97±1.0%). Biodistribution of the radiolabeled conjugate (99m)Tc-citro-folate was investigated in vivo using two groups of rats: FR saturated and unsaturated. These experiments showed high uptake of (99m)Tc-citro-folate in FR rich tissues and demonstrated its sensitivity and specificity in imaging ovary and uterus. Based on the demonstrated good radiolabeling and biodistribution properties, the compound (99m)Tc-citro-folate may potentially be used as a radiopharmaceutical agent for imaging the FR-positive tumors.

131I-Zn-Chlorophyll derivative photosensitizer for tumor imaging and photodynamic therapy.

In recent years, the photodynamic therapy studies have gained considerable attention as an alternative method to surgery, chemotherapy and radiotherapy which is commonly used to fight cancer. In this study, biological potentials of a benzyloxy bearing zinc(II) pheophorbide-a (Zn-PH-A) were investigated via in vivo and in vitro experiments. Zn-PH-A was labeled with (131)I with high efficiency (95.3 ± 2.7%) and its biodistribution studies were investigated on female Albino Wistar rats. The radiolabeled photosensitizer had been intravenously injected into the tail vein, and then the animals were sacrificed at 30, 60 and 120 min post injection. The percent of radioactivity per gram of organs (%ID/g) was determined. The radiolabeled Zn-PH-A showed high uptake in ovary. In addition, photodynamic therapy studies of the photosensitizer were conducted in EMT6, murine mammary carcinoma and HeLa, human cervix carcinoma cell lines. For the photodynamic therapy studies, the cells with Zn-PH-A were exposed to red light (650 nm) at the doses of 10-30 J/cm(2). The results showed that Zn-PH-A has stronger PDT effect in EMT6 than HeLa cell. Our present work demonstrates (131)I-labeled photosensitizer as a bifunctional agent (PDT and nuclear imaging) which could be improved in future by using EMT6 growing tumor in nude mice.

Evaluation of 99mTc-Pheophorbide-a use in infection imaging: a rat model.

This study aims to prepare (99m)Technetium Pheophorbide-a ((99m)Tc-PH-A) complex and evaluate its efficiency as an infection imaging agent. First, PH-A was obtained from Spirulina maxima algae, and the product compound was confirmed using (1)H NMR and MS (ESI) methods. The PH-A was then labeled with (99m)Tc using the tin chloride method and its biological efficacy as a potential radiotracer for Staphylococcus aureus (S. aureus) infection was evaluated in bacterially infected and sterile inflamed rats. The radiochemical stability of the (99m)Tc-PH-A in human serum was determined by thin-layer radiochromatography (TLRC). The radiochemical purity was 87±3.2% and remained constant at more than 80±0.1% even in serum for 120 min after radiolabeling. These experiments indicated that the ratio of (99m)Tc-PH-A uptake in bacterially infected muscle, as compared to normal muscle, [target/non-target (T/NT)=5.6 at 1h] was over four times higher than that in sterile inflamed muscle (T/NT=1.29 at 1h). Disappearance of activity from the kidney and liver indicated that the urinary and hepatobiliary systems were the normal routes of excretion of the complex. (99m)Technetium Pheophorbide prepared with high yield is able to localize well in the bacterially infected muscle of the rats and (99m)Tc-PH-A may be developed as a radiopharmaceutical agent to distinguish infection from inflammation by nuclear imaging.

Intracellular uptake study of radiolabeled anticancer drug and impedimetric detection of its interaction with DNA

Topoisomerase I inhibitor topotecan (TPT) is the only single-agent therapy certified for the remedy of repetitive small cell lung cancer (SCLC). In this study, TPT was labeled with (131)I via iodogen method and its quality control was determined using thin layer radiochromatography and paper electrophoresis methods. Intracellular uptake study was carried out with human lung adenocarcinoma cell line (A-549) and human lung fibroblast cell line (WI-38). The interaction of (131)I-TPT with healthy DNA and cancer DNA was also investigated using single-use sensor technology combined with electrochemical impedance spectroscopy (EIS). The change at the charge transfer resistance (Rct) obtained before/after interaction was evaluated. Similar to the results of intracellular uptake study, it was found that (131)I-TPT could more interact with the cancer DNA than healthy DNA according to the impedimetric results. (131)I-TPT is promising in terms of a new nuclear imaging agent for lung cancer.

In vitro evaluation, biodistribution in rats of radiolabeled raloxifene.

Raloxifene is a selective estrogen receptor modulator that produces both estrogen agonistic effects on bone and lipid metabolism and estrogen-antagonistic effects on uterine endometrium and breast tissue. In the present study, raloxifene was labeled with I-131 by iodogen method and investigated for its radiopharmaceutical potential. Radiolabeling yield is 91+/-0.7%, as determined by radio thin layer chromatography (RTLC). Results of in vitro study indicated (131)I-raloxifene has high stability (4h) in serum. Biodistribution study was carried out with Albino wistar female rats. The result has shown that the radioiodinated raloxifene has higher uptake in uterus than breast and ovarian.

Determination of iodine concentration in urine by isotope dilution analysis and thyroid volume of school children in the west coast of Turkey after mandatory salt iodization

Objective  This study was designed to evaluate iodine deficiency status in children 6–12 years in the west coast (Aegean Region) of Turkey after 5 years of mandatory iodine prophylaxis. A total of 2300 children from 72 populations (rural and urban area) were evaluated with urinary iodine excretion and thyroid volume.

In vitro evaluation of 99mTc-EDDA/tricine-HYNIC-Q-Litorin in gastrin-releasing peptide receptor positive tumor cell lines

Abstract Bombesin and its derivatives exhibit a high affinity for gastrin-releasing peptide receptor (GRPr), which is over-expressed in a variety of human cancers (prostate, pancreatic, lung, etc.). The aim of this study was to investigate the in vitro potential of the hydrazinonicotinamide (HYNIC)-Q-Litorin. 99mTc labeling was performed by using different co-ligands: tricine and ethylenediamine diacetic acid (EDDA). The radiochemical stability of radiolabeled peptide conjugates was checked at room temperature and in cysteine solution up to 24 h. The in vitro cell uptake of 99mTc-EDDA-HYNIC-Q-Litorin and 99mTc-tricine-HYNIC-Q-Litorin were evaluated on pancreatic tumor and control cell lines. Optimum specific activity and incubation time were determined for all the cell lines. The results showed that the cell uptake of the radiolabeled peptide conjugates in tumor cell lines were higher than in the control cell line. The findings of this study indicated the need for further development of in vivo study as a radiopharmaceutical for pancreatic tumor imaging.

Synthesis and biological evaluation of receptor-based tumor imaging agent: 99mTc-folate-glucaric acid

The aim of the present study was to prepare (99m)Tc-folate-glucaric acid and investigate the radiopharmaceutical potential for tumors imaging that over express folate receptor. Folate-glucaric acid was synthesized and the synthesized folate conjugate was confirmed with (1)H NMR and LC-MS/MS methods. Folate-glucaric acid was labeled with (99m)Tc, and its radiolabelling efficiency was found as 96 ± 2.0%. Biodistribution study of (99m)Tc-folate-glucaric acid was carried out in vivo using two groups of female Albino Wistar rats: folate receptor (FR) saturated and unsaturated. Biodistribution study showed that (99m)Tc-folate-glucaric acid indicated high uptake in folate receptor rich tissues such as breast, ovary and uterus. Therefore, (99m)Tc-folate-glucaric acid shows good radiolabeling and biodistribution in FR organs, the radiolabeled conjugate is a reason potentially useful radiopharmaceutical for detection of FR-positive tumors.