Molecular Radiotherapy with 177Lu-Immunoliposomes Induces Cytotoxicity in Mesothelioma Cancer Stem Cells In Vitro.

Malignant mesothelioma (MM) is a lethal tumor originating in the mesothelium with high chemotherapeutic resistance. Cancer stem cells (CSCs) persist in tumors and are critical targets responsible for tumor resistance and recurrence. The identification and characterization of CSCs may help develop effective treatment for MM. The objective of this study was to evaluate the therapeutic effect of molecular targeted radiotherapy by 177Lu-labeled immunoliposomes (177Lu-ILs) on CSCs of mesothelioma. MM CSCs were sorted based on CD26/CD24 expression level and their functional significances were established by small interference RNA. CSC potential of MM was evaluated for drug resistance, cell invasion, and cell growth rate in vitro. CSC metabolism was evaluated with the uptake of 18F-FDG. Therapeutic effects of 177Lu-labeled immunoliposomes targeting CD26 and CD24 were evaluated in vitro through proliferation and apoptotic assays. CSCs sorted from H28 cells exhibited significant drug resistance and enhanced proliferative activity as well as increased metabolism indicated by higher 18F-FDG uptake. Treatment with 177Lu-ILs, compared with 177Lu-CL and ILs, showed enhanced therapeutic effects on inhibition of proliferation, up-regulation of apoptosis, and suppression of CD26 and CD24 expression. Thus, our results suggest that molecular radiotherapy targeting both CD26 and CD24 could be a promising approach for CSC-targeting therapy for MM.

The use of matrigel has no influence on tumor development or PET imaging in FaDu human head and neck cancer xenografts.

BACKGROUND: In preclinical research Matrixgel(TM) Basement Membrane Matrix (MG) is used frequently for the establishment of syngeneic and xenograft cancer models. Limited information on its influence on parameters including; tumor growth, vascularization, hypoxia and imaging characteristics is currently available. This study evaluates the potential effect of matrigel use in a human head and neck cancer xenograft model (FaDu; hypopharyngeal carcinoma) in NMRI nude mice. The FaDu cell line was chosen based on its frequent use in studies of cancer imaging and tumor microenvironment. METHODS: NMRI nude mice (n = 34) were divided into two groups and subcutaneously injected with FaDu cells in medium either including (+MG) or excluding matrigel (-MG). In sub study I seven mice from each group (+MG, n = 7; -MG, n = 7) were (18)F- fluorodeoxyglucose ((18)F-FDG) PET/CT scanned on Day 5, 8, 12, 15, and 19. In sub study II ten mice from each group (+MG, n = 10; -MG, n = 10) were included and tumors collected for immunohistochemistry (IHC) analysis of tumor microenvironment including; proliferation ratio, micro vessel density, average vessel area, hypoxia, nuclear density, and necrosis. Tumors for IHC were collected according to size (200-400 mm(3), 500-700 mm(3), 800-1100 mm(3)). RESULTS: FDG uptake and tumor growth was statistically compatible for the tumors established with or without MG. The IHC analysis on all parameters only identified a significantly higher micro vessel density for tumor size 500-700 mm(3) and 800-1100 mm(3) and average vessel area for tumor size 500-700 mm(3) in the -MG group. Comparable variations were observed for tumors of both the +MG and -MG groups. No difference in tumor take rate was observed between groups in study. CONCLUSIONS: Matrigel did not affect tumor growth or tumor take for the FaDu xenograft model evaluated. Tumors in the -MG group displayed increased angiogenesis compared to the +MG tumors. No difference in (18)F-FDG PET uptake for tumors of different groups was found. Based on these observations the influence of matrigel on tumor imaging and tumor microenvironment seems minor for this particular xenograft model.

18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial.

BACKGROUND: The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ((18)F-NaF) and (18)F-fluorodeoxyglucose ((18)F-FDG). METHODS: In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent (18)F-NaF and (18)F-FDG PET-CT, and invasive coronary angiography. (18)F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of (18)F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction. FINDINGS: In 37 (93%) patients with myocardial infarction, the highest coronary (18)F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40-2·25] vs highest non-culprit 1·24 [1·06-1·38], p<0·0001). By contrast, coronary (18)F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40-2·13] vs 1·58 [1·28-2·01], p=0·34). Marked (18)F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal (18)F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61-2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09-1·19] vs 1·01 [0·94-1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21-29] vs 18% [14-22], p=0·001). INTERPRETATION: (18)F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease. FUNDING: Chief Scientist Office Scotland and British Heart Foundation.

Targeted PET/CT imaging of vulnerable atherosclerotic plaques: microcalcification with sodium fluoride and inflammation with fluorodeoxyglucose.

A significant majority of atherosclerotic plaque ruptures occur in coronary arteries exhibiting none or only modest luminal narrowing on coronary angiography. Emerging data suggest the biological composition of an atherosclerotic plaque (vulnerability to rupture) rather than its degree of stenosis or size is the major determinants for acute clinical events. Thus, the pursuit for noninvasive molecular imaging probes that target plaque composition, such as inflammation and/or microcalcification is a creditable goal. 18 F-fluorodioxyglucose (18 F-FDG) is a metabolic probe that can be imaged using positron emission tomography (PET)/computer tomography (CT) technology to target plaque macrophage glucose utilization and inflammation. Vascular plaque 18 F-FDG uptake has been linked to cardiovascular events such as myocardial infarction and stroke. More recently, another molecular probe 18 F-sodium fluoride (18 F-NaF) was introduced for PET imaging, which targets active microcalcifications in atherosclerotic plaques. Little is known regarding the role of early microcalcification in the initiation and progression of plaque, partly because of lack of a noninvasive imaging modality targeting molecular calcification. 18 F-NaF PET/CT imaging could provide new insights into the complex interaction of plaque, and facilitate understanding the mechanism of plaque calcification. Moreover, when these 2 molecular probes, 18 F-FDG and 18 F-NaF, that target distinct biological processes in an atherosclerotic plaque are used in combination, they may further elucidate the link between local inflammation, microcalcification, progression to plaque rupture, and cardiovascular event.

Triglyceride-Rich Lipoprotein-Mediated Polymer Dots for Multimodal Imaging Interscapular Brown Adipose Tissue Capillaries.

Brown adipose tissues (BATs) have been identified as a promising target of metabolism disorders. [18F]FDG-PET (FDG = fluorodeoxyglucose; PET = positron emission tomography) has been predominantly employed for BAT imaging, but its limitations drive the urgent need for novel functional probes combined with multimodal imaging approaches. It has been reported that polymer dots (Pdots) display rapid BAT imaging without additional cold stimulation. However, the mechanism by which Pdots image BAT remains unclear. Here, we made an intensive study of the imaging mechanism and found that Pdots can bind to triglyceride-rich lipoproteins (TRLs). By virtue of their high affinity to TRLs, Pdots selectively accumulate in capillary endothelial cells (ECs) in interscapular brown adipose tissues (iBATs). Compared to poly(styrene-co-maleic anhydride)cumene terminated (PSMAC)-Pdots with a short half-life and polyethylene glycol (PEG)-Pdots with low lipophilicity, naked-Pdots have good lipophilicity, with a half-life of about 30 min and up to 94% uptake in capillary ECs within 5 min, increasing rapidly after acute cold stimulation. These results suggested that the accumulation changes of Pdots in iBAT can reflect iBAT activity sensitively. Based on this mechanism, we further developed a strategy to detect iBAT activity and quantify the TRL uptake in vivo using multimodal Pdots.

Fluoro-deoxy-glucose uptake in the mylohyoid muscle: a common misconception.

AIM: The mylohyoid muscle is often believed to exhibit high physiologic fluoro-deoxy-glucose (FDG) uptake. Aim of this study was to use PET/MR for adequately assessing the normal FDG distribution in floor of the mouth (FOM) muscles and neighboring major salivary glands. MATERIALS AND METHODS: Patients scanned with a simultaneous PET/MRI system for initial staging or follow-up of head and neck tumors, with no malignant lesions in salivary glands or in FOM, were included. Volumes-of-interest (VOIs) were positioned separately for bilateral mylohyoid, digastric, genioglossus, and geniohyoid muscles, based on T2-weighted and T1-weighted images, and for bilateral parotid, submandibular, and sublingual glands in the same way. SUVmax was measured for each VOI. RESULTS: Six hundred and ninety-two VOIs were positioned. FDG uptake in mylohyoid (SUVmax = 1.94 ± 0.37) and digastric muscles (SUVmax = 2.01 ± 0.37) were significantly higher compared to that in geniohyoid (SUVmax = 1.67 ± 0.53) and genioglossus muscles (SUVmax = 1.75 ± 0.54) (Friedman's test; P < 0.001). FDG uptake in the sublingual glands (SUVmax = 3.77 ± 1.63) was significantly higher compared to the parotid glands (SUVmax = 2.34 ± 0.60) and submandibular glands (SUVmax = 2.51 ± 0.59) (Wilcoxon signed-ranks test; P < 0.001). FDG uptake in sublingual glands was significantly higher than FDG uptake in the mylohyoid muscles (P < 0.001). FDG uptake in the parotid, submandibular, and sublingual glands was inversely correlated to the age of subjects (Spearman' rho coefficient: -0.397/P = 0.004; -0.329/P = 0.021; -0.535/P < 0.001, respectively). CONCLUSION: The sublingual glands yield the highest physiologic FDG uptake in the FOM. High FDG uptake in the mylohyoid muscle is a common misconception.

Mechanism of reduced myocardial glucose utilization during acute hypertriglyceridemia in rats.

PURPOSE: The purpose of the research is to study the effect of acute inhibition of intravascular lipolysis on myocardial substrate selection during hypertriglyceridemia using in vivo radiotracer analysis and positron emission tomography. PROCEDURES: We induced acute hypertriglyceridemia in vivo using an intravenous infusion of Intralipid 20% (IL) without and with acute inhibition of fatty acid delivery from circulating triglycerides with injection of Triton WR-1339 (TRI) during a euglycemic-hyperinsulinemic clamp in Wistar rats. We determined the effect of TRI on myocardial uptake of circulating triglycerides and free fatty acids using intravenous injection of [(3)H]-triolein and [(14)C]-bromopalmitate, respectively. Myocardial blood flow, oxidative metabolism, and metabolic rate of glucose (MMRG) were determined using micro-positron emission tomography (microPET) with [(13)N]-ammonia, [(11)C]-acetate, and 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG). RESULTS: TRI reduced myocardial incorporation of [(3)H]-triolein but not [(14)C]-bromopalmitate showing that it selectively reduces myocardial fatty acid delivery from circulating triglycerides but not from free fatty acids. IL reduced myocardial blood flow and MMRG by 37% and 56%, respectively, but did not affect myocardial oxidative metabolism. TRI did not abolish the effect of IL on myocardial blood flow and MMRG. CONCLUSIONS: Hypertriglyceridemia acutely reduces myocardial blood flow and MMRG in rats, but this effect is not explained by increased myocardial fatty acid delivery through intravascular triglyceride lipolysis.

Biomaterials in repairing rat femoral defects: In vivo insights from small animal positron emission tomography/computed tomography (PET/CT) studies.

Biomaterials coated with artificial extracellular matrices (aECM) are intended to support the healing of critical size bone defects. This pilot study investigated (i) the feasibility of dual-tracer PET/CT imaging for functional characterization of biomaterial-assisted bone healing in a rat femoral defect model and (ii) the bone healing ability of polycaprolactone-co-lactide (PCL) scaffolds, coated with various aECM consisting of collagen type I (Col) and glycosaminoglycans (GAGs) such as chondroitin sulfate (CS) or polysulfated hyaluronan (sHA3). [18F]FDG and [18F]fluoride PET 4 and 8 weeks after implantation of aECM-coated PCL scaffolds, which provide an in vivo measure of cellular activation and bone mineralization, respectively, combined with CT imaging (in vivo/ex vivo) and histological/immunohistochemical investigations (ex vivo) showed that coating with CS in particular is beneficial for bone healing. The possible involvement of COX-2 and TGase 2, key enzymes of inflammation and ECM remodeling, in these processes offers starting points for targeted adjuvant therapy in the course of various bone healing phases. Our investigations show the feasibility of the selected dual-tracer approach for PET/CT imaging. In principle, this approach can be extended by further PET tracers for the functional characterization of physiological processes such as hypoxia/reperfusion or selected molecular players.

Association between carotid 18F-NaF and 18F-FDG uptake on PET/CT with ischemic vascular brain disease on MRI in patients with carotid artery disease.

OBJECTIVE: Atherosclerosis is a dynamic and complex process characterized by the formation and progression of plaque mediated by various pathophysiologic steps including inflammation and calcification. The present study aimed to evaluate the association between carotid 18F-sodium fluoride (NaF) and 18F-fluorodeoxyglucose (FDG) uptake with the severity of ischemic vascular brain disease on MRI in patients with carotid artery disease. METHODS: A total of 28 patients who were scheduled to undergo clinically indicated carotid endarterectomy or stenting for carotid artery disease were examined with 18F-NaF and 18F-FDG PET/CT and brain MRI. The PET/CT images were evaluated by qualitative and semiquantitative analyses. The maximum standardized uptake value (SUV) for the plaque and the average of mean SUV within the lumen of both internal jugular veins was calculated, and the target-to-blood pool ratio (TBR) was determined. The ischemic vascular brain disease on MRI was graded separately in the bilateral hemisphere as 0, 1, 2, and 3, with 0 being absent and 3 being the most severe. RESULTS: In two patients, only a unilateral carotid artery was analyzed because of previous indwelling stent. 18F-NaF focal uptake was observed in 50 carotid arteries. 18F-FDG focal uptake was observed in 47 carotid arteries. The mean (± SD) 18F-NaF TBR (2.93 ± 0.89) was significantly higher than the mean (± SD) 18F-FDG TBR (2.41 ± 0.84) (p < 0.001). The mean (± SD) values of 18F-NaF TBR were 2.63 ± 0.76 in grade 1, 2.90 ± 0.91 in grade 2, and 3.81 ± 0.60 in grade 3. Significant differences in 18F-NaF TBR were observed between grades 1 and 3 (p < 0.001) and grades 2 and 3 (p = 0.02). The mean (± SD) values of 18F-FDG TBR were 2.35 ± 0.77 in grade 1, 2.23 ± 0.48 in grade 2, and 2.87 ± 1.32 in grade 3. No significant differences in 18F-FDG TBR were noted between any of the ischemic vascular brain disease grades. CONCLUSIONS: These preliminary results suggest that carotid 18F-NaF uptake in patients with carotid artery disease may be associated with the severity of the ischemic vascular brain disease observed on MRI.

Comprehensive molecular imaging of malignant transformation of giant cell tumour of bone reveals diverse disease biology.

Malignant transformation of giant cell tumour of the bone is extremely rare. In addition, bone transformation in giant cell tumour may occur in different phases. With conventional X-rays, CT scans or MRIs, it may be challenging to distinguish among different phases of bone transformation, normal bone, soft tissue disease and bone disease (benign vs malignant lesions) and changes in multiple organs such as lung, liver and lymph nodes unless every lesion is biopsied, which is not practical. Molecular imaging with different isotopes (Tc-99m phosphonate, 2-deoxy-2-(18F)fluoro-d-glucose and sodium fluoride-18) may help to better characterise the disease. We hypothesised that molecular imaging could offer qualitative and quantitative characterisation of all stages of bone formation, destruction, reactivity or neoplasia in a patient with giant cell tumour of the bone, and we present the first case of molecular imaging where bone formation was seen in multiple soft tissues, such as lungs, muscles, lymph nodes and liver.

Reference values for fluorine-18-fluorodeoxyglucose and fluorine-18-sodium fluoride uptake in human arteries: a prospective evaluation of 89 healthy adults.

OBJECTIVE: Reference values of fluorine-18-fluorodeoxyglucose (F-FDG) and fluorine-18-sodium fluoride (F-NaF) uptake in human arteries are unknown. The aim of this study was to determine age-specific and sex-specific reference values of arterial F-FDG and F-NaF uptake. PARTICIPANTS AND METHODS: Uptake of F-FDG and F-NaF was determined in the ascending aorta, aortic arch, and descending thoracic aorta. In addition, F-FDG uptake was determined in the carotid arteries and F-NaF uptake was determined in the coronary arteries. Arterial F-FDG and F-NaF uptake were quantified as the blood pool subtracted maximum activity concentration in kBq/ml (BS F-FDGmax and BS F-NaFmax, respectively). In addition to determining reference values, we evaluated the influence of age and sex on BS F-FDGmax and BS F-NaFmax. RESULTS: Arterial F-FDG and F-NaF uptake was assessed in 89 healthy adults aged 21-75 years (mean age: 44±14 years, 53% men). Both BS F-FDGmax and BS F-NaFmax increased with age. BS F-FDGmax increased with age in the descending aorta (ß=0.28; P=0.003), whereas BS F-NaFmax increased with age in the ascending aorta (ß=0.18; P<0.001), aortic arch (ß=0.19; P=0.006), descending aorta (ß=0.33; P<0.001), and coronary arteries (ß=0.20; P=0.009), respectively. BS F-FDGmax and BS F-NaFmax were not influenced by sex, except for BS F-FDGmax in the ascending aorta. CONCLUSION: Prospective evaluation of 89 healthy adults generated age-specific and sex-specific reference values of arterial F-FDG and F-NaF uptake. Our findings indicate that arterial F-FDG and F-NaF uptake tend to increase with age.

Novel imaging in advanced prostate cancer.

PURPOSE OF REVIEW: Prostate cancer (PCa) is the most commonly diagnosed noncutaneous cancer and second leading cause of death in men. Imaging evaluation of PCa is challenging because of the prostate's deep pelvic location, its complex zonal anatomy and its multifocal nature. Novel imaging modalities are needed to improve detection, reassessment in biochemical relapse, and disease progression in advanced metastatic stages. RECENT FINDINGS: Current imaging modalities have distinct strengths. However, all lack the ability to diagnose micrometastases, differentiate high from low-grade disease and diagnose advanced disease, especially at low prostate specific antigen values. There is a need to combine the existing imaging methods with concepts utilizing tumor biology to differentiate biologically aggressive from indolent tumors. PET imaging with novel tracers facilitate improved imaging of PCa, but also usher in new compounds that could be useful for directing treatment as well. Most tracers have limited sensitivity, with the exception of prostate-specific membrane antigen (PSMA)-targeting tracers, that offer relatively higher sensitivity and specificity. SUMMARY: PSMA-PET appears promising in improving the imaging yield particularly in recurrent and advanced disease states. Incorporating PSMA-PET in these settings could open or prolong windows along the trajectory of the disease that could allow new treatments or more effective use of currently existing treatments. Prospective studies focusing on novel imaging enhancement and integration with therapeutic applications are needed.

131I-labeled chitosan hydrogels for radioembolization: A preclinical study in small animals.

INTRODUCTION: The purpose of the study was to examine potential of 131I-labeled chitosan hydrogels (Chi) for treatment of liver cancer. METHODS: Orthotopic hepatoma was induced by McA-RH7777-fLuc cells (1×107) that were injected into the left hepatic lobe of rats. Ten days later, tumor-bearing rats evidenced by bioluminescence received 125I-labeled Chi with left hepatic artery access. Pharmacokinetics and excretion (n=8) and biodistribution (n=6/time point) were studied after injection. To examine therapeutic potential, animals (n=8/group) were also treated with Chi labeled with or without 131I. Changes in tumor volume by magnetic resonance (MR) imaging were studied. RESULTS: The rate of tumor induction assessed by bioluminescence imaging was 72% (68/95). Gamma counter and scintigraphy imaging analyses showed accumulation of 125I-labeled Chi dominantly in the liver. A small fraction of 125I-labeled Chi was detected in the stomach (2.02±3.07%ID) and muscle (1.37±1.48%ID) at 2 d post-treatment. Blood sample analysis showed the maximum blood concentration of 0.09±0.03%ID/mL, which peaked at 0.60±0.45 d. Over a 4-week period, 31.22±8.16%ID were excreted in the urine and 3.5±1.3% in the feces. Treatment of Chi (median, 876mm3; IQR, 496mm3-1413mm3) markedly reduced the extent of tumor growth, compared to controls (median, 12,085mm3; IQR, 7786mm3-25,832mm3; P<0.05 vs control). 131I Chi (median, 80mm3; IQR, 35mm3-172mm3; P<0.05 vs control) induced a greater tumor-suppressing effect, compared to Chi alone. CONCLUSIONS: In this study, we have characterized a new radioembolization device, 131I Chi, in vivo and provided evidence for its therapeutic potential. ADVANCES IN KNOWLEDGE: Transarterial embolization is a conceivable treatment option for patients with inoperable liver cancer to mitigate the disease progression. Recently, we have developed chitosan-based hydrogel microparticles. In the present study, the hydrogel microparticles were radiolabeled with 131I for treatment of liver cancer. Our results demonstrated that a hepatic arterial injection of 125I-labeled Chi resulted in substantial liver accumulation, which was accompanied by virtually no extrahepatic deposition. The results of the present study also showed that administration of 131I Chi markedly suppressed tumor growth, compared to controls and to animals receiving unlabeled Chi. 131I-labeled chitosan hydrogel microparticles represent a new therapeutic approach for treatment of liver cancer.

Incidental focal 18F-FDG uptake in the frontal process of the maxilla on PET/CT: prevalence and clinical significance.

OBJECTIVE: We investigated the prevalence and clinical significance of incidental focal 18F-FDG uptake in the frontal process of the maxilla, mimicking malignancy on PET/CT. METHODS: From a total of 32,834 patients who underwent 18F-FDG PET/CT, patients with focal uptake in the frontal process of the maxilla were selected by a database search. For those patients, medical records including relevant imaging studies were reviewed. RESULTS: Thirty-nine patients (0.12 %) demonstrated focal uptake on PET/CT. On CT of PET/CT, all lesions showed ground-glass attenuation with or without bony expansion, consistent with fibrous dysplasia. When comparing previous PET/CT, follow-up PET/CT, and CT, a significant difference in degree of 18F-FDG uptake was noted, with no associated change in the size of maxillary lesions. There were no patients who had symptoms or signs related to maxillary lesions during follow-up. CONCLUSION: Focal 18F-FDG uptake in the frontal process of the maxilla is a rare, incidental, and persistent finding with variable uptake and can represent a benign condition.

Glucuronate-modified, long-circulating liposomes for the delivery of anticancer agents.

Liposomes are useful as drug carriers in drug delivery systems, especially for drugs with severe side effects such as antitumor agents. The conventional formulations of liposomes are opsonized by plasma proteins in the bloodstream and trapped in the reticuloendothelial system (RES). Therefore, liposomes with reduced opsonization are expected to have prolonged circulation and to accumulate in tumor tissue due to the leaky endothelium of the tissue. To avoid RES trapping of liposomes, two approaches have been considered. Liposomes may mimic cells circulating in the blood to escape host recognition as foreign substances, or liposomes may be covered with a hydrophilic barrier to escape recognition. For the latter purpose, poly(ethylene glycol) is widely used. For the former purpose, here we focus on the characteristics, in vivo trafficking, and usage in cancer therapy of glucuronate-modified liposomes. Glucuronate-modified liposomes bind to a lower extent to macrophage-like cells in vitro and passively accumulate in tumor tissue evaluated by a technique using positron emission tomography. Glucuronate-modified liposomes with extended circulation are useful for delivering anticancer agents to tumors and reducing the toxic side effects of the agents.

¹8F-FDG PET/CT: a review of diagnostic and prognostic features in multiple myeloma and related disorders.

Conventional radiographic skeletal survey has been for many years the gold standard to detect the occurrence of osteolytic lesions in patients with multiple myeloma (MM). However, the introduction of more sensitive imaging procedures has resulted in an updated anatomic and functional Durie and Salmon "plus" staging system and has remarkably changed the diagnostic and prognostic approach to this tumor. It is now established that (18)fluorine-fluorodeoxyglucose ((18)F-FDG) positron-emission tomography (PET) combined with low-dose computed tomography (CT), shortly designated PET/CT, exhibits a higher screening and diagnostic sensitivity and specificity over the skeleton X-ray. In patients with monoclonal gammopathy of undetermined significance and in those with smoldering MM, PET/CT is consistently unable to detect focal and/or diffuse marrow abnormalities. Conversely, based on a systematic review of 18 studies comprising almost 800 MM patients, PET/CT was able to detect MM osteolytic lesions with a sensitivity of approximately 80-90% and a specificity of 80-100%. Importantly, a poor degree of concordance has also been emphasized between PET/CT and whole-body magnetic resonance imaging (WB-MRI) in that when both techniques were applied to the same patients, double-positive results were recorded in approximately 30% of the cases, but in the majority of them, a higher number of lesions were revealed with PET/CT than with MRI. Double-negative results, on the other hand, were found in about 22% of the patients. Because PET/CT is able to identify tumor foci throughout the body, it can be usefully applied to the study of solitary bone plasmacytoma and extra-medullary plasmacytoma: In both conditions, the detection of additional, previously overlooked sites of skeletal involvement would falsify the diagnosis of single-district disease, upstage the tumor, and therefore require a different therapeutic approach. In addition, although PET/CT is poorly sensitive to diffuse bone marrow infiltration, it can anticipate a site of impending fracture throughout the body and can discriminate old from new pathologic fractures. MRI should, however, be preferred when vertebral bodies are suspected to be involved and the risk of vertebral fracture is to be assessed. PET/CT is a sensitive and reliable procedure to evaluate the response to chemotherapy and/or radiotherapy, which is shown by a remarkable reduction and sometimes total disappearance of FDG accumulation in the involved bony structures, although these structures remain morphologically abnormal. Conversely, an increased focal uptake of FDG in apparent remission patients often precedes clinically overt relapse. PET/CT should be preferred to other imaging techniques to assess the remission status after autologous stem cell transplantation. In patients with primary and remission-induced non-secretory MM, the use of PET/CT may help to early detect single or multiple districts of focal non-secretory relapse. Osteonecrosis of the jaw, its location, and extent in MM patients receiving bis-phosphonates are better defined by both PET/CT and contrast-enhanced MRI compared with dental panoramic views derived from cone beam CT imaging. Little is known as to the possible role of PET/CT in the assessment of disease extension, tumor load, and response to therapy in patients with Waldenström's macroglobulinemia (WM). In a study conducted on 35 WM patients, comparative PET/CT before and after therapy was able to detect positive findings in 83% of the patients, in contrast with the previous results achieved with conventional imaging that reported visceral involvement in much lower percentages. Similarly scanty are the data on the use of PET/CT in localized and systemic amyloidosis, given the small number of patients studied so far. A retrospective study has shown that, at variance from (123)Iodine-serum amyloid P component ((123)I-SAP) scintigraphy, which was found to be positive in about one-third of the patients with localized amyloidosis, an increased FDG uptake was detected at the amyloid site in virtually all of them. On the contrary, none of the patients with systemic amyloidosis showed an increased FDG uptake in sites of known deposition, whereas (123)I-SAP scintigraphy tested positive in the large majority of them. In another study, however, no such remarkable difference of positive PET/CT scans between localized and systemic amyloidosis was reported. Finally, false-positive and false-negative PET/CT findings can occur in different conditions that should be kept in mind to avoid wrong or omitted diagnoses.

Teflon-induced granuloma: a false-positive finding with PET resolved with combined PET and CT.

Patients who have undergone thyroidectomy may have recurrent laryngeal nerve injury; until recently, Teflon injection was commonly used for vocal cord medialization. We present a case of a patient who underwent thyroidectomy who had significantly increased and unilateral (18)F-fluorodeoxyglucose uptake in the neck, which was found to be localized to the left vocal cord by use of combined positron emission tomography (PET) and CT, presumably because of a Teflon-induced granuloma. Knowledge of this potential source of false-positive PET interpretation because of its inability to precisely localize neoplastic lesions, and the use of combined PET and CT imaging, may allow precise diagnosis and prevention of unnecessary interventions.

Reflection of ¹8F-FDG accumulation in the evaluation of the extent of periapical or periodontal inflammation.

OBJECTIVES: To elucidate whether fluorine-18-labeled ((18)F) fluoro-2-deoxy-d-glucose (FDG) accumulation can reflect the extent of periodontal inflammation, periapical inflammation, or dental caries. STUDY DESIGN: (18)F-FDG accumulations on positron emission tomography (PET)-computed tomography (CT) were retrospectively compared with the size of the bone resorption areas caused by periodontal inflammation, periapical inflammation, or dental caries on panoramic radiographs, CT, and magnetic resonance imaging (MRI) in 44 subjects. RESULTS: A significant correlation was found between the size of the bone resorption area caused by periodontal (r = 0.595, P < .01) or periapical (r = 0.560, P < .01) inflammation and the highest standardized uptake value (SUVmax) of (18)F-FDG accumulation. A significant correlation was found between the periodontal (r = 0.622, P < .01) or periapical (r = 0.394, P < .01) inflammatory findings on MRI and the SUVmax of (18)F-FDG accumulation. The SUVmax of (18)F-FDG around most teeth with caries was under 1.5. CONCLUSIONS: (18)F-FDG accumulation reflects the extent of dental inflammation, not dental caries.