Radiolabeled polymeric NPs are widely used drug delivery systems in cancer therapy and imaging due to their easy and rapid formation. These systems provide several advantages for imaging and therapy of many diseases and cancers, such as increased sensitivity, better image quality, etc. In this study, Tc-99m radiolabeled PLGA nanoparticles were prepared in different conditions and these conditions were investigated. The amount of reducing agent, incubation temperature and time, and pH were investigated to obtain the 99mTc-PLGA nanoparticles with higher RCP (%). NPs were formed well with the nanoprecipitation method between 180-200 nm. Then, the optimum formulation was obtained with 50 mu l SnCl2 at pH 7 and 25 degrees C conditions for 30 minutes of incubation time. This formulation was found stable at 25 degrees C for 12 hours while showing 3 hours of stability at 37 degrees C. The data proved that PLGA NPs can be radiolabeled with Tc-99m at high efficiency and showed relatively high radiolabeling stability.

The kidneys play a vital role in filtration, excretion, and metabolic regulation, making accurate functional assessment essential for diagnosis, monitoring, and management of renal diseases. While conventional imaging modalities such as ultrasonography, computed tomography (CT), and multiparametric magnetic resonance imaging (MRI) provide structural and functional information, nuclear medicine techniques enable more detailed evaluation of renal physiology at the molecular level. This review provides a comprehensive overview of functional renal imaging using both conventional renal scintigraphy and emerging positron emission tomography (PET) radiopharmaceuticals. Established renal scintigraphy radiopharmaceuticals, including 99mTc-DTPA, 99mTc-DMSA, 99mTc-MAG3, and 99mTc-EC, have long been applied to assess glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). PET radiopharmaceuticals, offering higher sensitivity, superior quantification, and molecular insight, are increasingly investigated for similar purposes, with 68Ga-EDTA, 68Ga-DTPA, 68Ga-NOTA, 68Ga-DOTA, and 18F-FDS for GFR assessment and 11C-PABA, 18F-PFH, Re-(CO)3(18F-FEDA), and Al-18F-NODA-butyric acid for ERPF evaluation. Additional PET tracers, including 68Ga-IRDye800-tilmanocept, 18F-FDG, and 68Ga-PSMA-11, have been explored for glomerular mesangial function, renal tumors, and split renal function, respectively. By systematically summarizing both renal scintigraphy and PET approaches, this review highlights current and emerging PET radiopharmaceuticals for renal functional imaging and discusses their potential clinical applications and future perspectives in precision nephrology.

Staphylococcus aureus infection can result in a serious inflammatory condition of bone tissue, osteomyelitis with significant challenges in diagnostics. The cell surface components of the bacteria can serve as binding sites for the precise and targeted delivery of diagnostic imaging agents. We created a novel infection imaging substance using a Gallium 68 (Ga-68) labelled aptamer that specifically targets S. aureus bacteria. The targeting aptamer was selected by cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) procedure with affinity constant at 2260 ± 634 CFU/mL. the linear detection range was between 250 and 2 x 10 4 CFU/mL. the limit of detection for s. aureus was 171 CFU/mL. The aptamer was conjugated to Ga-68 by DOTA procedure. Radioactive assays in vitro were specific for S. aureus between 10 3 and 2x10 4 CFU/mL. The encouraging outcomes indicate that this aptamer probe holds substantial promise for future in vivo experimentation, which might aid in clarifying its suitability for diagnosing S. aureus.

Cancer, having quite high morbidity and mortality rates, has become a significant public health problem in recent years, and it is the second leading cause of death after heart disease in the world. Metastases are one of the most serious complications of cancer, and bone metastases are detected in 2/3 of metastatic cancer cases. General therapy approaches in bone metastases can be classified as surgery, bisphosphonates therapy, radiotherapy, and radionuclide therapy. Radionuclide therapy using alpha and beta emitting radionuclides is more selective and effective than other local and systemic treatment methods, and this feature provide several advantages over existing therapeutic methods. Radionuclide therapy used in bone metastasis for reducing the pain, killing tumor cells, prolonging life span, and improving quality of life. In recent years, alpha-emitting radiopharmaceuticals [such as Radium-223 (Ra-223) chloride] and beta-emitting radiopharmaceuticals [such as Strontium-89 (Sr-89) chloride, Lutetium-177 (Lu-177) labeled Ethylenediamine Tetra Methylene Phosphonic Acid (EDTMP), Samarium-153 (Sm-153) labeled EDTMP] are introduced in the clinic for especially the treatment of painful bone metastases and on the other hand new radiopharmaceutical development studies also continue intensively, like Actinium-225 labeled prostate-specific membrane antigen-617 (Ac-225-PSMA). Many studies have proven that using radiopharmaceuticals in the therapy of bone metastases improves the patient's general health, reduces pain and the risk of pathological fractures, and increases survival. This review presents an overview of radionuclide therapy used in bone metastases. In this context, general information about the radiopharmaceuticals is given, and the importance of the use of radiopharmaceuticals in bone metastases therapy is explained with experimental and clinical studies examples.

Radiotherapy is one of the cancer treatment options in which ionizing radiation is used. While the ionizing radiation used here damages the tumor cells, it also damages the surrounding healthy cells and tissues. One of the approaches used to reduce the undesirable side effects and increase the therapeutic efficacy of radiotherapy is the use of radiosensitizers. Up to now, different radiosensitizers have been investigated for this purpose and recently, nanotechnology-based radiosensitizer research has attracted much attention. In this study, the therapeutic efficacy of tumor-targeted, nano-sized liposomal radiosensitizers containing quantum dots-photosensitizer conjugate was evaluated in vivo. It was aimed to destroy more tumor cells by using same the radiation doses routinely used in cancer treatment in radiation oncology clinics or to destroy about the same amount of tumor cells by using lower radiation doses than the routinely used clinical dose. For this purpose, nano-sized, PEG-coated, and folic acid-modified tumor-specific liposomes loaded with quantum dots (QD = CdSe/ZnS) - photosensitizer (Ce6 = Clorine-e6) conjugate was prepared and their therapeutic efficacy was evaluated in 4T1 murine breast cancer cell tumor-bearing mice. Following the single dose of 10Gy 6 MV X-ray irradiation after administration of liposomal radiosensitizer, changes in animals' weights and tumor volumes were measured and animal survival was monitored to evaluate the efficacy of the treatment. Histopathological studies were also performed to examine possible damage to the tumor and normal tissues. In control groups, only X-ray irradiation was applied or no treatment was applied to mice. The results showed that the liposomal radiosensitizer plus radiotherapy killed more cancer cells than radiotherapy alone. While tumor volumes increased in the control group, approximately a 39% reduction in tumor volumes was observed in mice treated with x-ray irradiation following administration of the liposomal radiosensitizer. The obtained results showed that nano-sized liposomal radiosensitizers could be a promising radiosensitizer to achieve better treatment efficacy in radiotherapy by applying fewer radiation doses compared to clinically used radiation doses.

Abstract This study aims to develop a multifunctional liposomal radiosensitizer to destroy more tumor cells by using lower radiation doses compared to clinically used 6 MV X-ray doses. To achieve this aim, first Chlorine-e6 (Ce6) was covalently bound to functional groups of outer surfaces of quantum dots (QDs) through EDC/NHS reactions. Then, QDs-Ce6 conjugate loaded, nanosized, PEG-coated, and tumor-specific folic acid-modified immunoliposome dispersions were prepared by film method. Enhanced anti-proliferation activity of free and liposomal conjugate against 4T1 (murine breast cancer) cell lines was investigated at different X-ray doses (5, 10, 15, and 20 Gy). As a result, the best radiosensitizer effect was observed at a 5 Gy X-ray dose and it was found that following the X-ray irradiation, immunoliposome dispersions containing QDs-Ce6 conjugate killed 26.8 ± 1.7% more cancer cells than radiation alone.

Cancer is the major burden of disease worldwide. The folate receptor, as a specific tumor target, is over-expressed in many types of cancer including ovarian carcinomas, breast, colon, renal, and lung tumors. Nuclear medicine hybrid imaging modalities, such as SPECT/CT, provide both metabolic and anatomic information. Therefore, specific contrast agents are essentially needed. Liposomes are favorable systems with many advantages. The aim of this study was to formulate liposomal imaging agents for molecular tumor imaging by SPECT or SPECT/CT and evaluate their efficacy. Nanosized, polyethyleneglycolated, folate-conjugated and unmodified, diethylenetriaminepentaacetic acid-phosphatidylethanolamine containing, neutral and positively charged liposomes were formulated and characterized by mean particle size, zeta potential, and quantitative determination of the phospholipids in the liposomes. The binding of the synthetized imaging agents to 4T1 breast tumor cells was evaluated by fluorescence microscopy and radioactivity counting. Folate-conjugated neutral and positively charged liposomes were found to be effective as tumor imaging agents exhibiting an almost 3-fold increased uptake and brighter fluorescence microscopy images than unmodified ones in in vitro experiments using 4T1 breast tumor cells. These results could be considered as an important step towards the development of folate-specific agents for tumor imaging by SPECT and SPECT/CT.

Parkinson's disease (PD) is characterized by the degeneration of the dopamine-producing cells in the substantia nigra. Early diagnosis and therapy is essential at the molecular level before initiation of symptomatic changes. Blood-brain barrier (BBB) penetration still remains a major challenge. Increased brain penetration and targeting can be achieved by formulating nanosized drug delivery systems using liposomes and niosomes. Other studies have been performed using pramipexole, but our study is novel in evaluating the penetration and antiparkinsonian effect of nanosized, polyethylene glycol (PEG) ylated pramipexole-encapsulated liposomes and niosomes. Nanosized, PEGylated, neutral and positively charged pramipexole-encapsulated liposomes and niosomes were formulated, characterized, and the release kinetics were evaluated. In vitro penetration of all formulations was evaluated using the BBB cell co-culture model. In vivo effectiveness of neutral, pramipexole-encapsulated liposomes and niosomes was evaluated in 6-hydroxydopamine (6-OHDA) lesioned rats by rotometer testing and autoradiography. All formulations exhibited approximately 10% encapsulation efficiency and around 100 nm particle sizes and fitted first-order release kinetics. All formulations were BBB permeable in vitro as determined by fluorescent images and fluorospectroscopy. Therefore, nanosized, neutral pramipexole-encapsulated niosomes showed better effects at a dosage approximately 9 times less than that administered using conventional pramipexole tablets for human in routine treatment. Nanosized PEGylated pramipexole liposomes and niosomes were blood brain barrier permeable. Nanosized pramipexole-encapsulated neutral niosomes showed potential therapeutic effects in a Parkinson's disease animal model depending on the nanosize and non-ionic surfactant properties of the niosomes. Further experiments are currently being performed to improve the therapeutic effects.

Magnetic resonance (MR) is one of the most widely used imaging modalities in contemporary medicine to obtain images of pathological areas. Still, there is a big effort to facilitate the accumulation of contrast in the required zone and further increase a local spatial concentration of a contrast agent for better imaging. Certain particulate carriers able to carry multiple contrast moieties can be used for an efficient delivery of contrast agents to areas of interest and enhancing a signal from these areas. Among those carriers, liposomes draw special attention because of their easily controlled properties and good pharmacological characteristics. To enhance the signal intensity from a given reporter metal in liposomes, one may attempt to increase the net quantity of carrier-associated reporter metal by using polylysine (PLL)-based polychelating amphiphilic polymers (PAP). In addition to heavy load of reporter metal onto the pharmaceutical nanocarrier (liposome), the accumulation of the contrast nanoparticles in organs and tissues of interest (such as tumors) can be significantly enhanced by targeting such particles both "passively," via the so-called enhanced permeability and retention (EPR) effect, or "actively," using various target-specific ligands, such as monoclonal antibodies. Combining three different properties-heavy load with gadolinium (Gd) via the liposome membrane-incorporated PAP and tumor specificity mediated by the liposome-attached mAb 2C5-in a single nanoparticle of long-circulating (PEGylated) liposomes could provide a new contrast agent for highly specific and efficient tumor MRI.

OP03 Selective extraction of medically-related radionuclides from proton-irradiated thorium targets

Theranostic liposomes carry both the therapeutic active ingredients and the contrast agent into one delivery system. Codelivery of imaging contrast agent and chemotherapeutic drugs can provide real-time validation of the targeting strategy, resulting in an another step forward for individual-based therapy. The aim of this study was the incorporation of different drugs used in the diagnosis and treatment of tumors into one delivery system to develop nanosized, polyethylene glycol (PEG)-coated, different charged theranostic liposomes. Different charged liposomes consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or Phospholipon (R) 90G (PL 90G; Phospholipid GmbH, Cologne, Germany), cholesterol, poly(ethylene glycol)2000/phosphatidyl ethanolamine (PEG(2000)-PE), stearylamine (SA) or dicetyl phosphate (DCP), and diethylenetriamine pentaacetate/PE (DTPA-PE) as bilayer ingredients and 5-florouracil (5-FU) as active substance were prepared by the film technique. Characterization, 5-FU in vitro release, cytotoxicity, and physical stability studies were performed. Particle size of all liposomes was 100-150 nm. Difference was not noted between encapsulation efficiency (EE%) of neutral DPPC and PL 90G liposomes containing 5-FU. EE% of charged DPPC liposomes was higher than that of charged PL 90G liposomes. PL 90G containing liposomes had a higher phospholipid amount than the same formulation of DPPC liposomes. DPPC containing different charged liposomes were selected for cytotoxicity studies. Different charged DPPC liposomes had the same antitumoral activity with the free 5-FU solution on MCF-7 cell lines. Liposome dispersions were more stable from the point of particle-size change and 5-FU leakage during storage at refrigerated temperature. The results of this study are very encouraging for the development of theranostic liposome formulations as a targeted delivery system for drugs, such as 5-FU, used both in therapy and imaging.

Molecular imaging is a relatively new discipline with a crucial role in diagnosis and treatment tracing of diseases through characterization and quantification of biological processes at cellular and sub-cellular levels of living organisms. These molecular targeted systems can be conjugated with contrast agents or radioligands to obtain specific molecular probes for the purpose of diagnosis of diseases more accurately by different imaging modalities. Nowadays, an interesting new approach to molecular imaging is the use of stealth nanosized drug delivery systems such as liposomes having convenient properties such as biodegradability, biocompatibility and non-toxicity and they can specifically be targeted to desired disease tissues by combining with specific targeting ligands and probes. The targeted liposomes as molecular probes in molecular imaging have been evaluated in this review. Therefore, the essential point is detection of molecular target of the disease which is different from normal conditions such as increase or decrease of a receptor, transporter, hormone, enzyme etc, or formation of a novel target. Transport of the diagnostic probe specifically to targeted cellular, sub-cellular or even to molecular entities can be performed by molecular imaging probes. This may lead to produce personalized medicine for imaging and/or therapy of diseases at earlier stages.

Among currently used cancer imaging methods, nuclear medicine modalities provide metabolic information, whereas modalities in radiology provide anatomical information. However, different modalities, having different acquisition times in separate machines, decrease the specificity and accuracy of images. To solve this problem, hybrid imaging modalities were developed as a new era, especially in the cancer imaging field. With widespread usage of hybrid imaging modalities, specific contrast agents are essentially needed to use in both modalities, such as single-photon emission computed tomography/computed tomography (SPECT/CT). Liposomes are one of the most desirable drug delivery systems, depending on their suitable properties. The aim of this study was to develop a liposomal contrast agent for the diagnosis and molecular imaging of tumor by SPECT/CT. Liposomes were prepared nanosized, coated with polyethylene glycol to obtain long blood circulation, and modified with monoclonal antibody 2C5 for specific tumor targeting. Although DTPA-PE and DTPA-PLL-NGPE (polychelating amphilic polymers; PAPs) were loaded onto liposomes for stable radiolabeling for SPECT imaging, iopromide was encapsulated into liposomes for CT imaging. Liposomes [(DPPC:PEG2000-PE:Chol:DTPA-PE), (PL 90G:PEG2000-PE:Chol:DTPA-PE), (DPPC:PEG2000-PE:Chol:PAPs), (PL 90G:PEG2000-PE:Chol:PAPs), (60:0.9:39:0.1% mol ratio)] were characterized in terms of entrapment efficiency, particle size, physical stability, and release kinetics. Additionally, in vitro cell-binding studies were carried out on two tumor cell lines (MCF-7 and EL 4) by counting radioactivity. Tumor-specific antibody-modified liposomes were found to be effective multimodal contrast agents by designating almost 3–8 fold more uptake than nonmodified ones in different tumor cell lines. These results could be considered as an important step in the development of tumor-targeted SPECT/CT contrast agents for cancer imaging.

Among different imaging modalities, Positron Emission Tomography (PET) gained importance in routine hospital practice depending on ability to diagnose diseases in early stages and tracing of therapy by obtaining metabolic information. The combination of PET with Computed Tomography (CT) forms hybrid imaging modality that gives chance to obtain better images having higher resolution by fusing both functional and anatomical images in the same imaging modality at the same time. Therefore, better contrast agents are essentially needed. The advance in research about developing drug delivery systems as specific nanosized targeted systems gained an additional importance for obtaining better diagnosis and therapy of different diseases. Liposomes appear to be more attractive drug delivery systems in delivering either drugs or imaging ligands to target tissue or organ of diseases with higher accumulation by producing in nano-scale, long circulating by stealth effect and specific targeting by modifying with specific ligands or markers. The combination of positron emitting radionuclides with liposomes are commonly in research level nowadays and there is no commercially available liposome formulation for PET imaging. However by conjugating positron emitter radionuclide with liposomes can form promising diagnostic agents for improved diagnosis and following up treatments by increasing image signal/contrast in the target tissue in lower concentrations by specific targeting as the most important advantage of liposomes. More accurate and earlier diagnosis of several diseases can be obtained even in molecular level with the use of stable and effectively radiolabeled molecular target specific nano sized liposomes with longer half-lived positron emitting radionuclides.

Currently used imaging modalities such as scintigraphy, computed tomography, magnetic resonance imaging and ultrasonography require the sufficient intensity of a corresponding signal from an area of interest to differentiate this area from the surrounding tissues. Targeting of various reporter moieties directly to the specific organs, tissues or tumors provide the highest dose of drug directly where it is needed. Many different types of nanoparticles are currently being studied for applications in nanomedicine. Among particulate drug carriers, liposomes are one of the most extensively studied and possess the most suitable characteristics for encapsulation of many drugs, genes, and diagnostic (imaging) agents. Among the many potential targets for such nanocarriers, tumors have been most often investigated. This review attempts to summarize the currently available information regarding liposomal nanocarriers for cancer imaging.

Recent research into the complex and varied components of rheumatoid arthritis (RA) is leading to the development of more effective targets for pharmaceutical approach than even before. Current treatment of RA frequently includes the use of nonsteroidal anti-inflammatory drugs, such as Diclofenac sodium (DFNa) in spite of the severe adverse effects. Local application and incorporation of the drugs in liposome based formulations may reduce those side effects and improve the efficacy of drugs by reducing the availability of them in systemic circulation and increasing accumulation and retention time in the sites of inflammation. Herein, anti-inflammatory efficacy of the DFNa containing lipogelosome formulations (L1J1) was evaluated and found that L1J1 elicits a better anti-inflammatory efficacy after a single dose i.a. administration in comparison with commercial product, VE-CP, which is used topically. Histopathological examination of the opened joints showed that joints treated with L1J1, had significantly (p < 0.05) lower scores than contra lateral control joints for inflammatory changes in the synovium. These results were also confirmed by biodistribution studies.

To further increase the therapeutic activity of drugs known to act on intracellular target sites, in vivo drug delivery approaches must actively mediate the specific delivery of drug molecules to the subcellular site of action. We show here that surface modification of nanocarriers with mitochondriotropic triphenylphosphonium cations facilitates the efficient subcellular delivery of a model drug to mitochondria of mammalian cells and improves its activity in vitro and in vivo.