Radiopharmaceutical Encapsulated Liposomes as a Novel Radiotracer Im - aging and Drug Delivery Protocol.

Nuclear medicine specialty involves the administration of unsealed radioactive substances to patients to allow specific diagnostics and treatments using radiopharmaceuticals, radiotracers, and materials. Developing a radiopharmaceutical must involve considering and addressing some limitations such as its retention by unintended organs, which can influence patient and worker safety, imaging findings, and diagnostic and therapeutic accuracy. This paper presents data on the changing biodistribution, localization, stability, and accuracy patterns of radiopharmaceuticals by liposome encapsulation. METHODS: Data are presented for 5 male New Zealand white rabbits. They were injected intravenously with the 99mTc-liposomes encapsulated MIBI through a marginal ear vein, and whole-body images were acquired using a dual-head gamma camera. Cationic PEGylated liposomes were prepared using the conventional thin-film-hydration method. The liposomes were tested for particle size, zeta potential, high-performance-liquid-chromatography (HPLC), and toxicity. RESULTS: The liver activity was slightly greater than or equivalent to heart uptake, using 99mTcsestamibi, MIBI, without liposome as a reference. The absorbed doses in myocardium cells after injecting rabbits with 99mTc-MIBI labeled with free positive lower pH liposomes was greater than in the liver, whereas 99mTc labeled with encapsulated MIBI within positive liposomes showed a significantly higher heart-to-liver ratio. The heart-to-spleen activity uptake ratio in 99mTc-MIBI was higher than or equal to one but increased in 99mTc labeled with MIBI and free positive liposomes. Injecting rabbits with 99mTc labeled with encapsulated MIBI raised myocardium uptake to 2-4 times more than the spleen. Heart-to-bowel activity began to rise with 99m Tc-labeld-MIBI and liposomes. CONCLUSION: This study provides findings in radiopharmaceutical biodistribution using liposomal agents. Adding free liposomes using a pH gradient technique enhanced the uptake and localization of the radiotracer. However, tracer encapsulation during the formation of the liposomes showed even better specificity.

Enhanced Efficacy of Radiopharmaceuticals When Using Technetium-99m-Labeled Liposomal Agents: Synthesis and Pharmacokinetic Properties.

Challenges posed by the retention of radiopharmaceuticals in unintended organs affect the quality of patient procedures when undergoing diagnostics and therapeutics. The aim of this study was to formulate a suitable tracer encapsulated in liposomes using different techniques and compounds to enhance the stability, uptake, clearance, and cytotoxic effect of the radiopharmaceutical. Cationic liposomes were prepared by a thin-film method using dipalmitoyl phosphatidylcholine (DPPC) and cholesterol. Whole-body gamma camera images were acquired of intravenously injected New Zealand rabbits. Additionally, liposomes were assessed using stability, toxicity, zeta potential, and particle size tests. In the control cases, Technetium-99m (99mTc)-sestamibi exhibited the lowest heart uptake the blood pool and delayed images compared to both 99mTc-liposomal agents. Liver and spleen uptake in the control samples with 99mTc-sestamibi increased in 1-h-delayed images, unlike with 99mTc-liposomal agents, which were decreased in delayed images. The mean maximum count in the bladder for 99mTc-sestamibi loaded liposomes 1 h post-injection was 2354.6 (±2.6%) compared to 178.4 (±0.54%) for 99mTc-sestamibi without liposomes. Liposomal encapsulation reduced the cytotoxic effect of the sestamibi. 99mTc-MIBI-cationic liposomes exhibited excellent early uptake and clearance compared to 99mTc-MIBI without liposomes. Adding cholesterol during liposome formation enhanced the stability and specificity of the targeted organs.

Impact of 18F-2-fluoro-2-deoxy-D-glucose PET/computerized tomography on the initial staging and changing the management intent in head and neck squamous cell carcinoma.

OBJECTIVE: To assess the role of 18F-FDG PET/CT in initial staging of head and neck squamous cell carcinoma and its impact on changing the management compared to other conventional methods. PATIENTS AND METHODS: A prospective study of 31 patients (21 male and 10 female), mean age 49.3 ± 12.1 years with histologically confirmed squamous cell carcinoma of the head and neck (nasopharynx was the commonest cancer in 15 patients (48.4%), poorly differentiated grade represented 64.5% of all tumors. Initial staging was achieved according to routine physical examination, endoscopy, CT, U/S, MRI. RESULTS: The overall change in TNM staging by 18F-FDG PET/CT in relation to conventional methods was encountered in 15/31 patients (48.4%). PET/CT changed; T staging in three patients (9.6%), upstaging in two patients and downstaging in one patient. PET/CT upstaged all 13/31 patients in N staging (41.9%). 18F-FDG PET/CT changed; M staging in 3/31 (9.6%) patients, upstaging in two and downstaging in one patient. PET/CT results caused radiotherapy modification in 21/31 patients (67.7%). PET/CT detected intra-parotid nodule in four patients, so additional radiation was added to the parotid in the treatment field. Retropharyngeal nodes were detected by PET/CT in three patients that were missed by conventional imaging. 18F-FDG PET/CT detected two patients of thyroid papillary carcinoma and one case of sigmoid neoplasm confirmed by histopathology. CONCLUSION: 18F-FDG-PET/CT is considered a valuable diagnostic test in head and neck squamous cell carcinoma at initial assessment which would change staging and radiotherapy planning and hence proper management.

Preclinical Assessment of 99mTc-Labeled Liposome Agents as an Effective Tracer in Nuclear Medicine.

This study assessed the use of 99mTc-liposome agents for nuclear medicine purposes. Methods: A variety of 99mTc-liposome formulations were compared with common lymphoscintigraphic agents, including 99mTc-labeled regular sulfur colloid and 99mTc-labeled human serum albumin, besides assisting the use of positively charged liposomes in rabbits. Ten male rabbits (2-2.5 kg) were anesthetized with ketamine and xylazine intramuscularly. Then, they were injected with different 99mTc-liposome agents subcutaneously in the dorsum of each hind foot over the region of the metatarsals at the midline, as well as intravenously. Dynamic (1 min) scintigraphic γ-camera images were acquired in a 256 × 1,024 matrix both early and 60 min after injection. Afterward, the tissue biodistribution was determined by calculating the percentage injected dose per organ for each 99mTc agent and studying the heart-to-liver, heart-to-bone marrow, and heart-to-kidney ratios. Results: All agents demonstrated good migration from the injection site to the blood pool but not to lymphatic drainage. Agents were starting to clear out rapidly after 60 min. Conclusion: 99mTc-liposome imaging can be used to develop novel liposome compositions with improved cardiac diagnostic and drug delivery characteristics.

Diagnostic performance of 18F-2-fluoro-2-deoxy-D-glucose PET/computerized tomography in identifying bone marrow infiltration in new patients with diffuse large B-cell lymphoma and Hodgkin lymphoma.

OBJECTIVE: To compare between F-2-fluoro-2-deoxy-D-glucose PET/computerized tomography (F-FDG PET/CT) and routine iliac bone marrow biopsy (BMB) in assessment of bone marrow infiltration (BMI) in Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL) patients at initial presentation. PATIENTS AND METHODS: A retrospective analysis of 138 patients (50 Hodgkin lymphomas, 88 DLBCLs). The study included 70 males and 68 females with median age of 43 years. All patients underwent F-FDG PET/CT and iliac crest BMB before treatment. Any focal or patchy FDG uptake in the bone marrow, superior-to hepatic uptake was interpreted as abnormal with or without corresponding CT changes. Treatment response was evaluated clinically with each cycle of chemotherapy, radiologically after three cycles and at the end of treatment. RESULTS: The overall diagnostic performance showed significant higher sensitivity of F-FDG PET/CT than that of BMB (73.9 versus 62.5%, P = 0.046), while the specificity was higher in BMB than in F-FDG PET/CT (100% in BMB versus 93.5% in F-FDG PET/CT). In Hodgkin lymphoma, sensitivity, negative predictive value (NPV) and accuracy were significantly higher in F-FDG PET/CT compared with BMB, being 87.5, 94.4 and 96% versus 50, 81 and 84% (P = 0.02, 0.03, 0.04, respectively). However, for DLBCL patients, almost comparable results were found between both tests in terms of sensitivity, NPV and accuracy (66.7, 83.9 and 81.8% versus 68.8, 84.9 and 88.6%, respectively). After PET/CT scan, 12 patients (8.6%) were upstaged to stage IV, eight of them were negative by BMB. CONCLUSION: F-FDG PET/CT seemed to be an excellent diagnostic test in assessment of BMI at initial assessment and staging of Hodgkin lymphoma and DLBCL patients.