Radiolabeling, quality control and kit formulation of a new 99m Tc-labeled antibiotic: 99m Tc-doxycycline hyclate

Since radiolabeled antibiotics specifically bind to the bacterial components they are promising radiopharmaceuticals for the precise diagnosis and detection of infectious lesions. Doxycycline hyclate (DOX) was chosen to investigate as a new radiolabeled antibacterial agent since its bacteriostatic activity against a wide variety of microorganisms. The aim of the present study is to develop simple and easy formulation of DOX with 99m Tc ready to use kit. 99m Tc-DOX was developed and standardized under varying conditions of reducing and antioxidant agent concentration, pH, radioactivity dose and reducing agent type. Labeling studies were performed by changing the selected parameters one by one and optimum labeling conditions were determined. After observing the conditions for maximum labeling efficiency and stability, lyophilized freeze dry kits were prepared accordingly. Radiochemical purity was determined with RTLC and RHPLC which was found more than >95 %. Two different freeze dry kits were formulated with optimum labeling conditions. The improved kits were found stable up to 6 months. © 2013 Akadémiai Kiadó, Budapest, Hungary.National Council for Scientific Research: Tubitak-110 S 229 09DPT001Acknowledgments This study was supported by The Scientific and Technological Research Council of Turkey (Tubitak-110 S 229). The authors would like to acknowledge the support of T.R. Prime Ministry State Planning Organization Foundation Grant Project Number: 09DPT001 for TLC Scanner. Also the authors thank to Ege University Nuclear Medicine Department technicians for their technical assistance for the animal experiments. -

Comparative bone uptake study of alendronate sodium from vaginal suppositories prepared with polyethylene glycol and massa estarinum bases [Polietilen glikol ve massa estarinum si{dotless}vaglari{dotless} kullani{dotless}larak hazi{dotless}rlanan vajinal supozituvarlardan sali{dotless}nan alendronat sodyumun kemik tutulumunun karşi{dotless}laşti{dotless}rmali{dotless} incelenmesi]

The aim of this study was to compare the bone uptake of alendronate sodium (ALD) from vaginal suppositories prepared with massa estarinum AB (ME) and polyethylene glycol 1500 (PEG) bases. For this purpose, ALD was radiolabeled with 99mTecnetium Pertechnetate (99mTc) by direct method. Radiochemical purity and stability of 99mTc-ALD was performed with chromatographic studies. 99mTc-ALD containing suppositories were prepared with ME and PEG bases. Physical properties of suppositories were evaluated. The physicochemical diffusion study was carried out to compare the release of ALD from different suppository bases. The bone uptake of 99mTc-ALD was observed by gamma scintigraphy studies. 99mTc-ALD containing suppositories were administrated to rabbits via vaginal route. The scintigraphic images were obtained with a gamma camera at different time intervals up to 240 minutes. According to our studies, radiochemical purity of 99mTc-ALD was observed more than 95% up to 6 hours. At 240 minutes of physicochemical diffusion studies, released ALD has 0.620 ± 0.091 mm and 10.465 ± 0.651 mm diameter zone from ME and PEG base suppositories respectively. According to the gamma scintigraphy studies, although no bone uptake observed after ME suppositories application, rabbit's bones were clearly visible after PEG suppositories applied. The results of physicochemical diffusion and gamma scintigraphy studies were found compatible in each other

Preparation of 99mTc-isosulfan blue for lymph node localization in rats 99mTc-isosulfan blue for lymph node localization

PubMed ID: 27756051The sentinel lymph node (SLN) is defined as the first regional lymph node to receive lymphatic drainage from a malignant tumor. Therefore, this node is a “sentinel” for second metastatic lymph node stations and for labeling regional tumor spread. For SLN detection, many surgeons preferred a combination of a preoperative injection of radiolabeled colloid and the intraoperative injection of blue dye. Under this combination protocol, nodes are considered to be “sentinel nodes” if they are radioactive and blue. The aim of this study is to develop a new single agent that combines both detection methods. For this purpose Isosulfan Blue (ISB) was radiolabeled by 99mTc with high labeling yield and stability. In vivo gamma scintigraphy studies were performed with rats. According to the scintigraphic studies, 99mTc-ISB shows rapid and high accumulation in both axillary (ALN) and popliteal lymph node (PLN). After the imaging study, extremity was opened and nodes were scanned for the radioactivity. According to performed study the lymph nodes were clearly seen to become blue and carried compound was sufficient to allow identification with a gamma probe. In conclusion, 99mTc-ISB has the potential to facilitate lymphatic mapping and subsequent sentinel node biopsy for solid malignancies such as breast cancer and melanoma. © 2016 Elsevier Lt

Exploiting the extemporaneousness of radiopharmaceuticals: Radiolabeling stability under diverse conditions

Radiopharmaceuticals are radioactive drugs, with a very short shelf life, in most of the cases. The number of proceedings using radiopharmaceuticals increases each day worldwide and for many countries the price of radiopharmaceuticals can represent a limitation in the offer of this drug for more patients. Nonetheless, the shortage of important radionuclides is a serious issue and may also affect the use and distribution of these drugs for more patients globally, especially in low and middle income countries. In this direction, the need to avoid waste of these drugs is crucial. In this study we have evaluated the stability of two radiopharmaceuticals (MDP and DTPA) under different conditions in order to propose the extension of shelf life. The results showed that is possible to have stable radiopharmaceuticals (both MDP and DTPA) even 24hs post labeling process when storage properly. The data may represent an advance in the field of Radiopharmacy, providing news perspectives for radiopharmaceuticals shelf life. © 2022 Elsevier B.V.E-26//211.207/2021, E-26/202.320/2021; E-26/010.002362/2019, E-26/211.269/2021; Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq: 301069/2018-2; Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, FAPERJ: E-26/010.000981/2019, E-26/200.815/2021; Comissão Nacional de Energia Nuclear, CNEN: 01341.011064/2021-71This study was funded by Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State ( FAPERJ ) ( Cientista do Nosso Estado : E-26/200.815/2021 ; Rede NanoSáude : E-26/010.000981/2019 , Pesquisa na UEZO : E-26/010.002362/2019 ; Temáticos : E-26/211.269/2021 , Infraestrutura e Pesquisa na UEZO e UERJ : E-26//211.207/2021 , Bolsa de Pós Doutorado Senior (PDS): E-26/202.320/2021 ); CNPq (Bolsa de Produtividade 1B: 301069/2018-2 ) to Ralph Santos-Oliveira; National Nuclear Energy Commission (Bolsa de Pós-doutorado CNEN: 01341.011064/2021-71 ) to Martha Sahylí Ortega Pijeira

Effect of microemulsion formulation on biodistribution of 99mTc-Aprotinin in acute pancreatitis models induced rats

PubMed ID: 26923781Background: Aprotinin is a monomeric globular polypeptide, which derived from bovine lung tissue and theoretically attractive molecule in ameliorating the effects of acute pancreatitis. Acute pancreatitis is an inflammatory condition of the pancreas that is painful and at times deadly. Over the following two decades Aprotinin therapeutic potential on pancreatitis is proven experimentally, its clinical therapeutic success is limited due to low targeting to pancreas. Objective: The aim of this study was to evaluate the biodistribution of Technetium-99m (99mTc)-Aprotinin solution (99mTc-Aprotinin-S) and 99mTc-Aprotinin loaded microemulsion, which was prepared for the aim of treatment for acute pancreatitis. Method: Aprotinin was radiolabeled with 99mTc. Radiochemical purity was determined with radioactive thin layer chromatography studies. 99mTc-Aprotinin-S and 99mTc-Aprotinin loaded microemulsion (99mTc-Aprotinin-M) was administered to acute edematous, severe necrotizing pancreatitis and air pouch model induced rats. Tissue distribution of Aprotinin was investigated with gamma scintigraphy and biodistribution studies. Results: Aprotinin was radiolabeled by 99mTc with high radiochemical purity (95.430 ± 0.946%). The complex was found to be stable at room temperature up to 6 h. Animal studies have shown that similar to that of other small proteins Aprotinin is accumulated primarily in the kidney. The scintigraphy and biodistribution studies showed that, while i.v. administration of 99mTc-Aprotinin-S distributed mostly in kidneys and bladder, 99mTc-Aprotinin-M, with droplet size of 64.550 ± 3.217 nm, has high uptake in liver, spleen and pancreas. Conclusion: This might be concluding that microemulsions may be suggested as promising formulations for selectively targeting Aprotinin to pancreas inflammation. © 2016 Informa UK Limited, trading as Taylor & Francis Group

Gemcitabine hydrochloride microspheres used for intravesical treatment of superficial bladder cancer: a comprehensive in vitro/ex vivo/in vivo evaluation

Sinem Yaprak Karavana,1 Zeynep Ay Şenyiğit,2 Çağrı Çalışkan,3 Gülnur Sevin,4 Derya İlem Özdemir,2 Yalçın Erzurumlu,5 Sait Şen,6 Esra Baloğlu1 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Ege University, Izmir, Turkey; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Izmir Katip Çelebi University, Izmir, Turkey; 3Department of Radiopharmacy, Faculty of Pharmacy, Ege University, Izmir, Turkey; 4Department of Pharmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey; 5Department of Biochemistry, Faculty of Pharmacy, Ege University, Izmir, Turkey; 6Department of Pathology, Faculty of Medicine, Ege University, Izmir, Turkey Introduction: Bladder cancer is responsible for more than 130,000 deaths annually worldwide. Intravesical delivery of chemotherapeutic agents provides effective drug localization to the target area to reduce toxicity and increase efficacy. This study aimed to develop an intravesical delivery system of gemcitabine HCl (Gem-HCl) to provide a sustained-release profile, to prolong residence time, and to enhance its efficiency in the treatment of bladder cancer. Materials and methods: For this purpose, bioadhesive microspheres were successfully prepared with average particle size, encapsulation efficiency, and loading capacity of 98.4 μm, 82.657%±5.817%, and 12.501±0.881 mg, respectively. For intravesical administration, bioadhesive microspheres were dispersed in mucoadhesive chitosan or in situ poloxamer gels and characterized in terms of gelation temperature, viscosity, mechanical, syringeability, and bioadhesive and rheological properties. The cytotoxic effects of Gem-HCl solution, Gem-HCl microspheres, and Gem-HCl microsphere-loaded gel formulations were evaluated in two different bladder cancer cell lines: T24 (ATCC HTB4TM) and RT4 (ATCC HTB2TM). Results: According to cell-culture studies, Gem-HCl microsphere-loaded poloxamer gel was more cytotoxic than Gem-HCl microsphere-loaded chitosan gel. Antitumor efficacy of newly developed formulations were investigated by in vivo studies using bladder-tumor-induced rats. Conclusion: According to in vivo studies, Gem-HCl microsphere-loaded poloxamer gel was found to be an effective and promising alternative for current intravesical delivery-system therapies. Keywords: gemcitabine HCl, intravesical chemotherapy, superficial bladder cancer microspheres, mucoadhesive gel, in situ ge