Advanced multifunctional nano-lipid carrier loaded gel for targeted delivery of 5-flurouracil and cannabidiol against non-melanoma skin cancer.

Non-melanoma skin cancer is one of the most common malignancies reported around the globe. Current treatment therapies fail to meet the desired therapeutic efficacy due to high degree of drug resistance. Thus, there is prominent demand in advancing the current conventional therapy to achieve desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells. Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The current investigation has been designed to evaluate the safety and efficacy of developed 5-Flurouracil and cannabidiol loaded combinatorial lipid-based nanocarrier (FU-CBD NLCs) gel for the effective treatment of skin cancer. Initially, confocal microscopy study results showed excellent uptake and deposition at epidermal and the dermal layer. Irritation studies performed by IR camera and HET cam shows FU-CBD NLCs was much more tolerated and less irritant compared to conventional treatment. Furthermore, gamma scintigraphy evaluation shows the skin retention behavior of the formulation. Later, in-ovo tumor remission studies were performed, and it was found that prepared FU-CBD NLCs was able to reduce tumor volume significantly compared to conventional formulation. Thus, obtained results disclosed that permeation and disposition of 5-FU and CBD into different layers of the skin FU-CBD NLCs gel could be more potential carrier than conventional gel. Furthermore, prepared formulation showed greater tumor remission, better survival rate, reduction in tumor number, area, and volume with improved biochemical profile. Thus, prepared gel could serve as a promising formulation approach for the skin cancer treatment.

Alpha-ketoglutarate mediated hepatoprotection against alcohol induced toxicity: in vivo functional observation studies in Sprague Dawley rats using gamma scintigraphy.

Alcohol is the most abused psychoactive substance and known hepatotoxicant. Present study elucidates possible therapeutic effect of oral alpha-ketoglutarate (AKG) supplementation against alcohol induced hepatic dysfunction, using biochemical, histopathological and most importantly, in vivo functional imaging approaches. Animals were divided into three groups of 6 animals each. Group-I (control): Normal saline; Group-II: 20% (v/v) solution of ethanol (5 ml/day) intragastrically using oral gavage for 2 months. Group-III: ethanol treatment as in group-II along with AKG supplementation (2g/kg/bw; intragastrically using oral gavage for 2 months). In vivo hepatobiliary scintigraphy was performed in all animals using 99mTc-mebrofenin (99mTc-MEB) as radiotracer to determine changes in (a) Hepatic extraction fraction (HEF), for quantification of radiotracer uptake, (b) Time to reach maximum hepatic uptake (Tpeak), and (c) Time for hepatic uptake to reduce by 50% (T1/2peak). Biochemical (alanine aminotransferase, aspartate aminotransferase, reduced glutathione, superoxide dismutase, catalase, and lipid peroxidation) and histological parameters were also studied. Hepatic uptake and excretion kinetics using 99mTc-MEB scintigraphy showed prompt 99mTc-MEB clearance from liver in control group (HEF: 91.26 ± 2.32; Tpeak: 143 ± 23 sec; T1/2peak: 434 ± 41 sec), while it was significantly abnormal in ethanol group and showed less efficient radiotracer accumulation (HEF: 62.72 ± 5.6; Tpeak: 201 ± 33 sec; T1/2peak: 542 ± 52 sec). Supplementation of AKG along with ethanol significantly improved liver function (HEF: 76.42 ± 5.3; Tpeak: 155 ± 34 sec; T1/2peak: 455 ± 22 sec). Biochemical and histopathology parameters were correlative to findings of functional imaging study. Results strongly indicate hepatoprotective potential of AKG against alcohol-induced hepatic injury. Study further proposes the use of in vivo hepatobiliary scintigraphy for high throughput screening of other hepatoprotectants.

Estimation of radiation dose to patients from (18) FDG whole body PET/CT investigations using dynamic PET scan protocol.

BACKGROUND & OBJECTIVES: There is a growing concern over the radiation exposure of patients from undergoing 18FDG PET/CT (18F-fluorodeoxyglucose positron emission tomography/computed tomography) whole body investigations. The aim of the present study was to study the kinetics of 18FDG distributions and estimate the radiation dose received by patients undergoing 18FDG whole body PET/CT investigations. METHODS: Dynamic PET scans in different regions of the body were performed in 49 patients so as to measure percentage uptake of 18FDG in brain, liver, spleen, adrenals, kidneys and stomach. The residence time in these organs was calculated and radiation dose was estimated using OLINDA software. The radiation dose from the CT component was computed using the software CT-Expo and measured using computed tomography dose index (CTDI) phantom and ionization chamber. As per the clinical protocol, the patients were refrained from eating and drinking for a minimum period of 4 h prior to the study. RESULTS: The estimated residence time in males was 0.196 h (brain), 0.09 h (liver), 0.007 h (spleen), 0.0006 h (adrenals), 0.013 h (kidneys) and 0.005 h (stomach) whereas it was 0.189 h (brain), 0.11 h (liver), 0.01 h (spleen), 0.0007 h (adrenals), 0.02 h (kidneys) and 0.004 h (stomach) in females. The effective dose was found to be 0.020 mSv/MBq in males and 0.025 mSv/MBq in females from internally administered 18FDG and 6.8 mSv in males and 7.9 mSv in females from the CT component. For an administered activity of 370 MBq of 18FDG, the effective dose from PET/CT investigations was estimated to be 14.2 mSv in males and 17.2 mSv in females. INTERPRETATION & CONCLUSIONS: The present results did not demonstrate significant difference in the kinetics of 18FDG distribution in male and female patients. The estimated PET/CT doses were found to be higher than many other conventional diagnostic radiology examinations suggesting that all efforts should be made to clinically justify and carefully weigh the risk-benefit ratios prior to every 18FDG whole body PET/CT scan.

Differential diagnosis of parkinsonian syndromes using F-18 fluorodeoxyglucose positron emission tomography.

INTRODUCTION: Positron emission tomography (PET) imaging with F-18 fluorodeoxyglucose (FDG) has been used to identify characteristic patterns of regional glucose metabolism in patients with idiopathic Parkinson's disease (IPD) and the atypical parkinsonian syndromes of progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). We undertook this study to assess the utility of fluorodeoxyglucose-PET in the differential diagnosis of individual patients with clinical parkinsonism. "Visual" and "computer-supported" reading of the fluorodeoxyglucose-PET scans were used for image interpretation and compared with each other. METHODS: One hundred thirty-six parkinsonian patients were referred from movement disorder clinics in specialty neurology centers for the fluorodeoxyglucose-PET study. Imaging-based diagnosis was obtained by visual assessment of individual scans by a PET physician blinded to the clinical diagnosis and also by computer-assisted interpretation using statistical parametric mapping (SPM) analysis. The results were compared with a 2-year follow-up clinical assessment made by a movement disorder specialist. RESULTS: Concordance of visual evaluation of fluorodeoxyglucose-PET with clinical diagnosis was achieved in 91.7% of patients scanned, 97.6% IPD, 80% MSA, 76.6% PSP, and 100% CBS. Blinded computer assessment using SPM was concordant with the clinical diagnosis in 91% of cases evaluated (90.4% IPD, 80% MSA, 93.3% PSP, and 100% CBS). CONCLUSIONS: Fluorodeoxyglucose-PET performed at the time of initial referral for parkinsonism is useful for the differential diagnosis of IPD, PSP, MSA, and CBS. Computer-assisted methods can be used for objective evaluation especially when expert readers are not available.

Evaluation of three different 99mTc-based mock-venom agents for lymphoscintigraphy studies in preclinical models of peripheral snakebite envenomation.

Snakebite envenomation is one of the major public health concerns across many countries; with the WHO designating it as a 'priority neglected tropical disease' and stressing for a need to develop novel therapeutic strategies to reduce death and disability rate by end of 2030. Since a major component of venom; the high molecular weight (HMw) toxins enter the bloodstream through lymphatic system, research is focusing on modulating the lymphatic flow rate after topical application of suitable drug candidates. Present study compared the suitability of three radiopharmaceutical agents, namely 99mTc-Sulfur colloid (SC), 99mTc-Phytate (Phy) and 99mTc-Human serum albumin (HSA), to be used as mock-venom agent in studying modulation in lymphatic flow rate in preclinical models of peripheral snakebite envenomation using lymphoscintigraphy studies. The study was performed in 72 Sprague Dawley rats; divided into six groups of 12 rats each. Control groups were given intradermal injection (1.29-1.48 MBq in 100 µl normal saline) of either 99mTc-Phy/ 99mTc-SC/ 99mTc-HSA into the tail as 'mock-venom'. In respective test groups, commercially available topical formulation (Anobliss® Cream) containing Nifedipine (Nif; 0.3% w/w) and Lidocaine (Lid; 1.5% w/w) was applied topically over the animals' lower body (tail and hind limbs) immediately within 20s of administering intradermal injection of the radiopharmaceutical. Any modulation in lymph transit time from periphery to systemic circulation was assessed using lymphoscintigraphy by taking dynamic gamma-scintigraphy images of 60s each till 1 h post-injection of the test radiopharmaceuticals. Significant difference in movement of the three radiopharmaceuticals was noted in terms of their lymphatic movement. 99mTc-Phy did not show significant travel through the lymphatics and the liver was faintly visualized in control as well as test intervention groups. In case of 99mTc-SC, significant changes in movement of the radiotracer after topical application of Nif/Lid in the test intervention groups were clearly noted in comparison to control (P < 0.05). Multiple numbers of lymph nodes (LNs) could be clearly visualized in control (5 ± 1 LNs) and test intervention groups (3 ± 1 LNs). Liver uptake was more prominent in control animals and it reduced significantly in test intervention groups. On the other hand, 99mTc-HSA showed lesser number of lymph nodes and higher accumulation in liver as compared to 99mTc-SC, suggesting very fast movement of this radiopharmaceutical. Results indicates that 99mTc-SC could be used as a suitable agent to mimic lymphatic transit behavior of HMw toxin components of snake venom and could therefore be used as a model in studying the effect of any test pharmacological intervention in modulating lymphatic transit rate. Additional advantage could be a significant reduction in the need for sacrificing large number of animals, particularly during initial screening phase of drug development cycle.

Fabrication, characterization and evaluation of the efficacy of gelatin/hyaluronic acid microporous scaffolds suffused with aloe-vera in a rat burn model.

Burn induced injuries are commonly encountered in civilian and military settings, leading to severe morbidity and mortality. Objective of this study was to construct microporous bioactive scaffolds of gelatin-hyaluronic acid suffused with aloe-vera gel (Gela/HA/AvG), and to evaluate their efficacy in healing partial-thickness burn wounds. Scaffolds were characterized using Fourier transform-infrared spectroscopy, Scanning electron microscopy, and Thermo-gravimetric analysis to understand intermolecular interactions and morphological characteristics. In-vitro fluid uptake ability and hemolytic index of test scaffolds were also determined. In-vitro collagenase digestion was done to assess biodegradability of scaffolds. Wound retraction studies were carried out in Sprague Dawley rats inflicted with partial-thickness burn wounds to assess and compare efficacy of optimized scaffolds with respect to negative and positive control groups. In-vivo gamma scintigraphy using Technetium-99m labeled Immunoglobulin-G (99mTc-IgG) as imaging agent was also performed to validate efficacy results. Histological and immunohistochemical comparison between groups was also made. Scaffolds exhibited mircoporous structure, with pore size getting reduced from 41.3 ± 4.3 µm to 30.49 ± 5.7 µm when gelatin conc. was varied from 1% to 5%. Optimized test scaffolds showed sustained in-vitro swelling behavior, were biodegradable and showed hemolytic index in range of 2.4-4.3%. Wound retraction study along with in-vivo gamma scintigraphy indicated that Gela/HA/AvG scaffolds were not only able to reduce local inflammation faster but also accelerated dermis regeneration. Immunohistochemical analysis, in terms of expression levels of epidermal growth factor and fibroblast growth factor-2 also corroborated in-vivo efficacy findings. Gela/HA/AvG scaffolds, therefore, can potentially be developed into an effective dermal regeneration template for partial-thickness burn wounds.

18F-FDG 18F-FDG Positron Emission Tomography Imaging of Cortical Reorganization in Spinal Trauma.

Objective: Spinal cord injury (SCI) extensively impacts the sensorimotor reorganization in the brain. The effects can be both anatomical and functional. To date, not many studies using 18F-Fluoro-2-Deoxyglucose positron emission tomography (18F-FDG PET) to evaluate metabolic changes in the brain are done. Understanding such changes is crucial for developing clinical management and evidence-based rehabilitation strategies for these patients. Subjects and Methods: In this study, we compared 18F-FDG PET imaging of 6 SCI patients with complete paraplegia and 19 controls. Statistical parametric mapping software was utilized to compare the images on a voxel to voxel basis (significance level P < 0.05 and clusters having >50 voxels). Results: The study showed raised metabolism in supplementary motor areas, comprehension centers, some areas in the parietal and temporal lobe, putamen and cerebellum while reduced metabolic uptake in areas like anterior cingulate gyrus, hippocampus and sensory cortical areas when SCI patients were compared against healthy controls. The frontal lobe showed varied results where certain regions showed higher metabolism while the others showed lower in patients compared with controls. Conclusion: Cerebral deafferentation or disuse atrophy can be linked with reduced metabolism while raised uptake can be associated with initiation and planning of movement and cognitive changes in the brain posttrauma.

Genome-wide expression reveals potential biomarkers in breast cancer bone metastasis.

Breast cancer metastases are most commonly found in bone, an indication of poor prognosis. Pathway-based biomarkers identification may help elucidate the cellular signature of breast cancer metastasis in bone, further characterizing the etiology and promoting new therapeutic approaches. We extracted gene expression profiles from mouse macrophages from the GEO dataset, GSE152795 using the GEO2R webtool. The differentially expressed genes (DEGs) were filtered by log2 fold-change with threshold 1.5 (FDR < 0.05). STRING database and Enrichr were used for GO-term analysis, miRNA and TF analysis associated with DEGs. Autodock Vienna was exploited to investigate interaction of anti-cancer drugs, Actinomycin-D and Adriamycin. Sensitivity and specificity of DEGs was assessed using receiver operating characteristic (ROC) analyses. A total of 61 DEGs, included 27 down-regulated and 34 up-regulated, were found to be significant in breast cancer bone metastasis. Major DEGs were associated with lipid metabolism and immunological response of tumor tissue. Crucial DEGs, Bcl3, ADGRG7, FABP4, VCAN, and IRF4 were regulated by miRNAs, miR-497, miR-574, miR-138 and TFs, CCDN1, STAT6, IRF8. Docking analysis showed that these genes possessed strong binding with the drugs. ROC analysis demonstrated Bcl3 is specific to metastasis. DEGs Bcl3, ADGRG7, FABP4, IRF4, their regulating miRNAs and TFs have strong impact on proliferation and metastasis of breast cancer in bone tissues. In conclusion, present study revealed that DEGs are directly involved in of breast tumor metastasis in bone tissues. Identified genes, miRNAs, and TFs can be possible drug targets that may be used for the therapeutics. However, further experimental validation is necessary.

In-vitro and in-vivo functional observation studies to establish therapeutic potential of alpha-ketoglutarate against methotrexate induced liver injury.

BACKGROUND: Methotrexate (MTX) is widely used in chemotherapy but its associated hepatotoxicity is a major complication, limiting its use. This study evaluates possible therapeutic effect of oral alpha-ketoglutarate (AKG) supplementation against MTX-induced hepatotoxicity. METHODS: HepG2 cells were used to evaluate in-vitro cyto-protection conferred by AKG against MTX induced cytotoxicity. For in-vivo animal study, rats were divided into three groups. Group-I served as control. Group-II animals were administered single intraperitoneal injection of MTX (20 mg/kg/body weight), while Group-III received MTX as in group-II followed by oral AKG (2 gm/kg body weight) for 5 days. 99mTc-Mebrofenin hepatobiliary study was performed under a gamma camera to determine real time functional status of rats' livers. Multiple parameters concerning hepatic mebrofenin uptake and excretion, including Tpeak and T1/2 peak in control and treated animals were determined. Biochemical analysis of the liver homogenate in terms of hepatic enzyme activities in serum, antioxidant status, tissue factor activity, tissue collagen content and histological analysis of the liver tissue were also done. RESULTS: AKG supplementation significantly reversed MTX induced derangement in activities of serum liver enzymes [ALT and ALP (p = 0.003); AST (p = 0.005)], antioxidant status [LPO and GSH (p = 0.005); CAT (p = 0.004)], tissue factor activity (p = 0.005) and tissue collagen content (p = 0.005). Functional imaging confirmed that hepatic retention and fractional biliary excretion were significantly abnormal in MTX treated group (Tpeak: 234 s ± 40 s; T1/2 peak: 846sec ± 32sec) as compared to AKG supplemented group (Tpeak: 144 s ± 35sec; T1/2peak: 468sec ± 27sec). Hepatic extraction fraction (HEF) was 92.2 ± 1.8%, 48.7 ± 2.6% and 69.8 ± 4.3% in control, MTX and AKG supplemented rats respectively. CONCLUSION: 99mTc-mebrofenin imaging strongly suggests therapeutic action of AKG in protecting liver damage by MTX in rats. Functional imaging parameters correlated well with biochemical and histopathological findings.

F-18 fluorodeoxyglucose positron emission tomography/computed tomography in conjunctival melanoma with recurrence.

Ocular melanoma is classified under the category of noncutaneous melanomas. Noncutaneous melanomas are relatively rare. Ocular melanoma commonly arises from choroid. Conjunctival melanoma is a rare but potentially lethal form of ocular melanoma. It can invade locally. Systemic spread is seen in up to 25% of cases, often associated with lymph node involvement. Metastatic sites include the lungs, liver, gastrointestinal tract, and the central nervous system. F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET-CT) scanning is indicated for staging cutaneous melanoma patients. However, few studies have evaluated its role in the management of conjunctival melanoma. This case highlights the use of F-18 FDG PET/CT for imaging, preoperative staging, and evaluation for metastasis in conjunctival melanoma.

Prospective evaluation of CECT and 18F-FDG-PET/CT in detection of hepatic metastases.

OBJECTIVES: The purpose of this study was to evaluate the performance of F-fluorodeoxy-D-glucose (FDG)-PET/computed tomography (CT) and contrast-enhanced CT (CECT) in the detection and characterization of hepatic metastases. METHODS: Forty-five patients harboring an extrahepatic primary malignancy, with suspected hepatic metastases on clinical or ultrasonographic examination were enroled prospectively. Each patient underwent contrast-enhanced abdominal CT and F-FDG-PET/CT within 72 h of each other, reported by an experienced radiologist and nuclear medicine specialist, respectively in a blinded manner. CECT and PET-CT findings were compared and analyzed. Final diagnosis was based on histology and/or follow-up (ranging from 6 to 12 months). RESULTS: The sensitivity and specificity of CECT in the detection of hepatic metastases was 87.9 and 16.7%, respectively, whereas that of PET/CT was 97 and 75%, respectively. This study showed the superiority of PET/CT over CECT in the detection of hepatic metastases, irrespective of the primary site. This was especially owing to the latter's inability to reliably distinguish small (less than 15 mm) lesions as benign or malignant. CONCLUSION: Many studies have been conducted on the impact of FDG-PET/CT in the evaluation of hepatic metastases, especially from colorectal primary. Very few prospective studies, however, have been conducted on its role in evaluation of hepatic metastases from nongastrointestinal primaries. Despite its superior performance, it cannot replace CECT for this purpose, owing to the low but definite risk of false positivity based on PET-CT findings alone. Inclusion of CECT in PET/CT protocols may enable us to achieve a higher diagnostic accuracy. This suggests the need for a large prospective study with serial evaluations and pathological correlation.

99mTc-methionine scintimammography in the evaluation of breast cancer.

OBJECTIVE: The diagnostic utility of a C-methionine scan has been established in breast cancer. We were able to radiolabel methionine with Tc at our institute. Thus, we undertook clinical trials to determine the role of Tc-methionine scans in the detection of breast cancer. METHODS: Scintimammography was performed in 47 female (median age 44 years, range 28-68 years) patients having palpable breast masses. All of them underwent ultrasound, mammography, fine-needle aspiration cytology, and Tc-methionine scintimammography before surgery. The final diagnosis was made after histopathological examination. Tc-methionine scintimammography was done after injecting 555 MBq of radiotracer intravenously. The results of scintimammography were compared with histopathology. RESULTS: The histopathological findings were malignant in 33 (70%) and benign in 14 (30%) cases. Scintimammography showed true-positive findings in 29 patients out of 33 cases of breast cancer. True-negative findings were found in 13 out of 14 patients having benign breast lesions. The sensitivity, specificity, and positive predictive value were found to be 87.8, 92.8, and 96.6% respectively. CONCLUSION: Tc-methionine imaging can provide useful information with reasonably high sensitivity and specificity in evaluating patients having breast masses.

The importance of 18F-FDG PET/CT, CT and X-rays in detecting primary stage III A lung cancer and the incidence of extra thoracic metastases.

Lung cancer (LC) has an unfavorable prognosis especially when the disease is extensive at presentation. Accurate staging is therefore needed for treatment planning of these patients. In the present study the role of positron emission tomography/computerized tomography (PET/CT) in the detection of extra thoracic metastases in LC is being evaluated. In all 52 of our patients with stage IIIA or lower of LC disease, a whole body (18)F-FDG PET/CT was performed. All patients were also subjected to general clinical evaluation, chest X-rays and chest contrast enhanced CT (CECT) and were confirmed by histopathology or magnetic resonance imaging or radiology. Incidental extra thoracic malignant lesions were found by (18)F-FDG PET/CT in 9 out of the 52 patients (17.3%). No false positive lesions were found. As for the primary LC diagnosed by fine needle aspiration cytology (FNAC): (18)F-FDG PET/CT diagnosed all 52 cases, CECT detected 46 cases and chest X-rays detected 28 cases. The diagnostic accuracy was 100%, 92% and 53.8% respectively. As for the 9 cases with extrathoracic metastases diagnosed by (18)F-FDG PET/CT they were confirmed: by biopsy 6, by MRI 2 and by X-rays with or without biopsy 2. In conclusion, (18)F-FDG PET/CT had better diagnostic accuracy in diagnosing LC stage IIIA or lower, than CECT or chest X-rays. Extrathoracic metastases were high: 9/52 as diagnosed by (18)F-FDG PET/CT and standardized up take value.

FDG PET/CT with SPM Analysis in Early Diagnosis of Clinically Suspected Osmotic Demyelination Syndrome with Non-contributory MRI.

Early diagnosis is imperative for adequate management of patients with osmotic demyelination syndrome (ODS), which is usually a result of rapid shifts of osmolality secondary to rapid correction of hyponatremia. Magnetic resonance imaging (MRI) with its special sequences is the investigation of choice for early detection of the osmotic changes in the brain. We report a case of clinically suspected ODS with noncontributory MRI and positive fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) scan with statistical parametric mapping (SPM) analysis, which localized the focal hypermetabolism in the basal ganglia, thalamus, pons, and cerebellum.

Ventilation scintigraphy with lipophilic cationic compounds.

OBJECTIVE: On the basis of our hypothesis that lipophilic cations may be more suitable for ventilation lung scintigraphy than the conventional technetium-99m diethylenetriamine penta-acetic acid (Tc-DTPA), comparative studies were carried out. BASIC METHODS: The nebulization potential of nine routine radiopharmaceuticals was compared on medical and scintigraphy-specific nebulizers. This was followed by ventilation scintigraphy in 14 patients with chronic obstructive airway disease (n=13) or pulmonary embolism (n=1) where either 99mTc-methoxyisobutylisonitrile (n=10) or Tc-tetrofosmin (n=4) was used. Same-patient comparison with 99mTc-DTPA ventilation scan was available in six patients using the same acquisition protocol. Comparison with 99mTc-DTPA was made with respect to the nebulization rates, radioactivity delivered per unit of radioactivity available for inhalation, and regional distribution of inhaled counts. RESULTS: Lipophilic cation solutions had a significantly higher nebulization rate compared with 99mTc-DTPA using the medical nebulizer (235%, P<0.01) and 370% on scintigraphy-specific nebulizer (P<0.01). More than three times the counts of 99mTc-methoxyisobutylisonitrile or 99mTc-tetrofosmin was deposited in the body compared with Tc-DTPA aerosol per megabecquerel activity inhaled (1.5 vs. 0.4 kcounts/MBq) (P<0.001), preferentially in the lungs (75.2 vs. 65.2%), at the expense of oropharynx and stomach. Within the lungs, about 50% more counts were deposited in the outer one-third lung with lipophilic cations. Overall, therefore, more than 12 times the radioactivity deposition was achieved in the peripheral one-third of the lungs with the lipophilic cations. CONCLUSION: Ventilation lung scanning with lipophilic cations is a viable substitute of nanoparticle scintigraphy (technegas and pertechnegas, which are expensive and technically far more demanding).

Development and clinical study of submicronic-atropine sulphate respiratory fluid as a novel organophosphorous poisoning antidote.

CONTEXT: Increased use of organophosphate insecticides (OPI) and possibility of terror groups using stocks of nerve agents underscore the need to develop effective and safe antidotes. While intramuscular administration of antidotes like atropine sulphate (AS) has certain lacunae, intravenous route may not be always feasible in emergency field conditions. OBJECTIVE: Objective was (a) to develop a novel inhalable submicronic-AS respiratory fluid as potential antidote for OPI poisoning, (b) in-vitro and in-vivo evaluation in terms of respiratory fraction, and (c) clinical study to assess drug bioavailability in blood and atropinization pattern post-inhalation. METHODS: Formulation was optimized on the basis of particle size of aerosolized droplets and in-vitro nebulization rate. Anderson cascade impaction (ACI) studies were carried out to validate the advantage of test formulation in terms of respirable fraction. Six healthy volunteers were inhaled the test formulation and blood bioavailability and atropinization were noted serially. Gamma scintigraphy was used to quantify total and regional lung deposition of nebulized AS in-vivo. RESULTS: The formulation was optimized using 30% ethanol-saline with particle size in the range of 350-500 nm. In-vitro ACI data showed high respirable fraction (82.6 ± 3.1%) for the test formulation. In-vivo scintigraphy suggested whole lung deposition of 80.2 ± 6.8% of the total inhaled dose. Early blood bioavailability and atropinization pattern confirmed that therapeutic concentration of the drug in blood was reached within 5 min. CONCLUSIONS: 3% submicronic-AS respiratory fluid might be used as potential prophylactic/therapeutic option against OPI poisoning with several advantages over intramuscular injection, including early blood bioavailability and atropinization.

Characterization of 'cold' vertebrae on 18F-FDG PET/CT.

INTRODUCTION: A photon-deficient ('cold') vertebra on fluorine-18 fluorodeoxyglucose (F-FDG) PET is a known entity and can arise as a result of varying etiologies. A proper interpretation of this observation is required to make an accurate diagnosis for appropriate management. METHODS: Twelve cases with 'cold' vertebrae on F-FDG PET/computed tomography (CT) were selected and analyzed from a population of 600 patients with a known malignancy who had undergone whole-body F-FDG PET/CT for staging, disease viability assessment, response to treatment, or suspected recurrence purposes. The patterns were studied and correlated with clinical history and the results of the low-dose CT performed with the PET scan for attenuation correction and anatomical localization. RESULTS: The most common cause for cold vertebrae was found to be postexternal radiotherapy, causing photopenia involving multiple vertebrae corresponding to the radiotherapy portals. Two other causes found in the study were the destruction of the vertebral marrow cavity by metastatic tumor cells and vertebral hemangioma. Characteristic features of 'cold' vertebrae have been described in the study with illustrations. CONCLUSION: Pattern recognition coupled with clinical history and CT correlation of 'cold' vertebrae on F-FDG PET/CT can help in diagnosing the correct underlying etiology, which can help in better management of the patients.

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography imaging in response monitoring of extra-pulmonary tuberculosis.

Positron emission tomography/computed tomography (PET/CT) using 2-deoxy-2-(fluorine-18) fluoro-D-glucose ((18)F-FDG) has become a standard diagnostic modality in oncological practice. F18-FDG PET/CT is sensitive in detecting malignancy; however, specificity is low in differentiating infections or inflammatory diseases from tumor. In the present case study, we report a patient with postoperative carcinoma of tongue presenting with cervical lymphadenopathy and fever. The PET/CT scan showed metabolically active generalized lymphadenopathy, and a possibility of lymphoma was suggested. Fine needle aspiration cytology showed the Ziehl-Neelsen staining to be strongly positive for acid-fast bacilli and first line of antitubercular drug was administrated. Six months later after the initiation of therapy, a follow-up PET/CT showed remarkable improvement of the disease status. This case study illustrates that tubercular infection can be a pitfall in F18-FDG PET/CT imaging. PET positive lesions do not always indicate malignancy, and histological confirmation of lesions with biopsy should always be performed. Once diagnosed to be tubercular, FDG PET/CT is a powerful imaging tool in monitoring the therapy.

(11)C-Methionine positron emission tomography-computed tomography in localization of methoxyisobutyl isonitrile negative ectopic parathyroid adenoma.

Primary hyperparathyroidism is caused by parathyroid adenomas in 85% of the cases. Since parathyroid adenomas are known for their ectopic location, presurgical localization of the suspected site of adenoma is desirable. However, current imaging modalities are not always successful in localizing ectopic parathyroid adenomas. The aim of this case report is to show that (11)C-methionine positron emission tomography could accurately localize ectopic parathyroid adenomas in patients in whom conventional imaging had failed or is inconclusive.

A comparison study of (11)C-methionine and (18)F-fluorodeoxyglucose positron emission tomography-computed tomography scans in evaluation of patients with recurrent brain tumors.

INTRODUCTION: (11)C-methonine ([(11)C]-MET) positron emission tomography-computed tomography (PET-CT) is a well-established technique for evaluation of tumor for diagnosis and treatment planning in neurooncology. [(11)C]-MET reflects amino acid transport and has been shown to be more sensitive than magnetic resonance imaging (MRI) in stereotactic biopsy planning. This study compared fluorodeoxyglucose (FDG) PET-CT and MET PET-CT in the detection of various brain tumors. MATERIALS AND METHODS: Sixty-four subjects of brain tumor treated by surgery, chemotherapy, and/or radiotherapy were subjected to [(18)F]-FDG, [(11)C]-MET, and MRI scan. The lesion was analyzed semiquantitatively using tumor to normal contralateral ratio. The diagnosis was confirmed by surgery, stereotactic biopsy, clinical follow-up, MRI, or CT scans. RESULTS: Tumor recurrence was found in 5 out of 22 patients on [F-18] FDG scan while [(11)C]-MET was able to detect recurrence in 18 out of 22 patients in low-grade gliomas. Two of these patients were false positive for the presence of recurrence of tumor and later found to be harboring necrosis. Among oligodendroglioma, medulloblastoma and high-grade glioma out of 42 patients 39 were found to be concordant MET and FDG scans. On semiquantitative analysis, mean T/NT ratio was found to be 2.96 ± 0.94 for lesions positive for recurrence of tumors and 1.18 ± 0.74 for lesions negative for recurrence of tumor on [(11)C]-MET scan. While the ratio for FDG scan on semiquantitative analysis was found to be 2.05 ± 1.04 for lesions positive for recurrence of tumors and 0.52 ± 0.15 for lesions negative for recurrence of tumors. CONCLUSION: The study highlight that [(11)C]-MET is superior to [(18)F]-FDG PET scans to detect recurrence in low-grade glioma. A cut-off value of target to nontarget value of 1.47 is a useful parameter to distinguish benign from malignant lesion on an [(11)C]-MET Scan. Both [(18)F]-FDG and [(11)C]-MET scans were found to be useful in high-grade astrocytoma, oligodendroglioma, and medulloblastoma.