Radiolabeled nucleosides for predicting and monitoring the cancer therapeutic efficacy of chemodrugs.

Uncontrolled cell proliferation is an important hallmark of cancer. Cancer treatment with cytostatic chemodrugs usually results in insignificant changes in tumor size, and thus limits the applications of anatomical imaging modalities for determining the therapeutic efficacy. Positron emission tomography (PET) imaging with cell proliferation probes to assess the clinical outcome during or soon after treatment is becoming acceptable. At present, monitoring DNA synthetic pathways with radiolabeled nucleoside probes that are essential for cell proliferation has been considered a more specific approach to predict tumor response. Among the four nucleosides, thymidine analogues, such as (18)F-FLT, have undergone years of development for clinical practice, while cytidine, adenosine and guanosine analogues receive less attention. Recently, several literatures have demonstrated that PET imaging with radiolabeled cytidine and adenosine analogues may have potential to evaluate immune response after chemotherapy, and may enable the prognosis forecast. In this review, we summarize the results of recent preclinical and clinical studies regarding using radiolabeled nucleoside analogues for predicting and monitoring tumor response in cancer treatment. The preparation protocols of these nucleoside scintigraphic probes are also described.

Increased expression of cysteinyl leukotriene receptor-1 in the brain mediates neuronal damage and astrogliosis after focal cerebral ischemia in rats.

Cysteinyl leukotrienes are potent pro-inflammatory mediators. Cysteinyl leukotriene receptor 1 is one of the two cysteinyl leukotriene receptors cloned. We recently reported that cysteinyl leukotriene receptor 1 antagonists protected against cerebral ischemic injury, and an inducible expression of cysteinyl leukotriene receptor 1 was found in neuron- and glial-appearing cells after traumatic injury in human brain. To determine the role of cysteinyl leukotriene receptor 1 in ischemic brain injury, we investigated the temporal and spatial profile of cysteinyl leukotriene receptor 1 expression in rat brain from 3 h to 14 days after 30 min of middle cerebral artery occlusion, and observed the effect of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, on the ischemic injury. We found that cysteinyl leukotriene receptor 1 mRNA expression was up-regulated in the ischemic core both 3-12 h and 7-14 days, and in the boundary zone 7-14 days after reperfusion. In the ischemic core, cysteinyl leukotriene receptor 1 was primarily localized in neurons 24 h, and in macrophage/microglia 14 days after reperfusion; while in the boundary zone it was localized in proliferated astrocytes 14 days after reperfusion. Pranlukast attenuated neurological deficits, reduced infarct volume and ameliorated neuron loss in the ischemic core 24 h after reperfusion; it reduced infarct volume, ameliorated neuron loss and inhibited astrocyte proliferation in the boundary zone 14 days after reperfusion. Thus, we conclude that cysteinyl leukotriene receptor 1 mediates acute neuronal damage and subacute/chronic astrogliosis after focal cerebral ischemia.

Positron emission tomography for the assessment of myocardial viability in Kawasaki disease using different therapies.

13N-ammonia and 18F-fluorodeoxyglucose positron emission tomography (PET) of the heart were performed on 30 children with a history of Kawasaki disease. The results indicated PET abnormalities in 61.1% of patients during the acute and subacute stages and in 41.2% of patients in the convalescent stage of Kawasaki disease. Two-dimensional echocardiography and coronary angiography could not predict the myocardial viability and perfusion as well as PET. Different therapies during the acute stage of the disease did not effectively prevent myocardial damage, despite the absence of coronary arterial abnormalities. The patients who received 400 mg x kg(-1) x day(-1) of intravenous immunoglobulin (IVIG) for 5 days had a significantly lower incidence of PET abnormalities than those who received a single dose of 2000 mg x kg(-1) IVIG (P < 0.05).

Abdominal wall necrosis following transcatheter arterial chemoembolization for hepatocellular carcinoma.

A 76-year-old man, who had inoperable hepatocellular carcinoma, had been treated with transcatheter arterial chemoembolization (TACE) 11 times, percutaneous ethanol injection therapy three times and conformal radiotherapy once, all in other hospitals. At this admission, he developed myocutaneous necrosis in the right abdominal wall after TACE, via the collateral of the right internal mammary artery (IMA). Necrosis of the abdominal wall was due to ischemic changes caused by embolization of the distal branches of the IMA, which were aggravated by previous radiation therapy. We advise that embolization of the IMA in patients who have received radiotherapy should be avoided, if possible.

Clinical evaluation of the bone marrow imaging agent 99Tcm-phytate in the detection of bone metastases.

The aims of this study were to assess whether 99Tcm-phytate can detect metastatic skeletal lesions, and to compare it with 99Tcm-methylene diphosphonate (99Tcm-MDP) and 99Tcm-labelled human serum albumin nanocolloids (99Tcm-NC). Twenty-four patients with multiple bony metastases, investigated by 99Tcm-MDP whole-body scintigraphy, underwent 99Tcm-phytate bone marrow imaging. A separate bone marrow scintigram with 99Tcm-NC was performed in 20 of the patients. All of the metastatic lesions detected on the 99Tcm-phytate scintigrams exhibited photon-abundant foci only. Most of the 99Tcm-phytate scintigrams detected fewer metastatic lesions than the corresponding bone scintigrams. Visual comparison of the 99Tcm-NC images showed that 13 of 20 99Tcm-NC images were superior to the 99Tcm-phytate images in the detection of metastatic involvement of the skeleton. Thus 99Tcm-phytate should not be used as a bone marrow imaging agent for the detection of skeletal metastases.

Detection of anaerobic odontogenic infections by fluorine-18 fluoromisonidazole.

Odontogenic infections are a potential risk for patients who receive cervicofacial radiotherapy and should be treated before irradiation. Anaerobic microbial infections are the most common causes. This study assessed the value of the hypoxic imaging agent fluorine-18 fluoromisonidazole (FMISO) in detecting anaerobic odontogenic infections. Positron emission tomography (PET) imaging was performed at 2 h after injection of 370 MBq (10 mCi) of FMISO in 26 nasopharyngeal carcinoma patients and six controls with healthy teeth. Tomograms were interpreted visually to identify hypoxic foci in the jaw. All patients received thorough dental examinations as a pre-radiotherapy work-up. Fifty-one sites of periodontitis, 15 periodontal abscesses, 14 sites of dental caries with root canal infection, 23 sites of dental caries without root canal infection, and seven necrotic pulps were found by dental examination. Anaerobic pathogens were isolated from 12 patients. Increased uptake of FMISO was found at 45 out of 51 sites of periodontitis, all 15 sites of periodontal abscess, all 14 sites of dental caries with root canal infection, all seven sites of necrotic pulp and 15 sites of dental caries without obvious evidence of active root canal infection. No abnormal uptake was seen in the healthy teeth of patients or in the six controls. The diagnostic sensitivity, specificity, positive and negative predictive values, and accuracy of FMISO PET scan in detecting odontogenic infections were 93%, 97%, 84%, 99% and 96%, respectively. 18F-fluoride ion bone scan done in three patients showed that 18F-fluoride ion plays no role in the demonstration of anaerobic odontogenic infection. FMISO PET scan is a sensitive method for the detection of anaerobic odontogenic infections, and may play a complementary role in the evaluation of the dental condition of patients with head and neck tumours prior to radiation therapy.

Superscan in patients with nasopharyngeal carcinoma.

Bone scintigraphy plays an important role in the early detection of bone metastases in patients with nasopharyngeal carcinoma and serial scans may aid the clinician to assess the therapeutic response. A superscan is a pattern described as abnormal bone scan, indicating extensive bony metastases associated with various neoplastic diseases. Bone scans from 407 patients with nasopharyngeal carcinoma were reviewed retrospectively. Only six superscans (1.5%) were found. The appearance of a superscan is frequently accompanied by an abnormal titer of serological markers IgG-VCA and IgA-VCA, liver metastases, and poor survival. Although a superscan rarely occurs in nasopharyngeal carcinoma, its appearance may represent a poor prognosis in these patients.

Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of thymoma: a preliminary report.

Thymomas are lacking in malignant cytological features. Their staging is defined by the invasiveness of the tumour. This study aimed to analyse the uptake patterns of fluorine-18 fluorodeoxyglucose (FDG) in thymomas of different stages. FDG positron emission tomography (PET) scan was performed in 12 patients suspected of having thymoma and in nine controls. Qualitative visual interpretation was used to detect the foci with FDG uptake higher than that of normal mediastinum. Tumour/lung ratio (TLR) was calculated from the counts of ROIs over the mass and over comparable normal lung tissue in thymoma patients. Mediastinum/lung ratio (MLR) was calculated from the counts of ROIs over the anterior mediastinum and lung in controls. The PET scan patterns of distribution of foci with FDG uptake and TLRs were correlated with the computed tomography (CT) or magnetic resonance imaging (MRI) findings, and staging of the thymomas. Thymectomy was performed in ten patients and thoracoscopy was done in two patients. The results revealed ten thymomas (two stage I tumours, two stage II, four stage III and two stage IV, according to the Masaoka classification), and two cases of thymic hyperplasia associated with myasthenia gravis. Myasthenia gravis was also noted in four thymoma patients. FDG studies showed (a) diffuse uptake in the widened anterior mediastinum in patients with thymic hyperplasia, (b) confined focal FDG uptake in the non-invasive or less invasive, stage I and II thymomas, and (c) multiple discrete foci of FDG uptake in the mediastinum and thoracic structures in stage III and IV advanced invasive thymomas. The thymomas had the highest TLRs, followed by the TLRs of thymic hyperplasia and the MLRs of control subjects (P <0.005). No significant difference was found between thymomas in different stages or between thymomas with and thymomas without myasthenia gravis. In comparison with CT and/or MRI, FDG-PET detected more lesions in patients with invasive thymomas and downgraded the staging of thymoma in four patients. Our preliminary results suggest that FDG-PET is useful in the assessment of the invasiveness of thymomas, and may have the potential to differentiate thymomas from thymic hyperplasia.

The "Fisherman's Waders" sign in a bone scan of inferior vena cava thrombosis associated with nephrotic syndrome.

This paper presents a 61-year-old male patient with nephrotic syndrome, hypercoagulability and IVC thrombosis. Increased soft tissue uptake below the level of the mid chest was seen in his bone scan. The term "Fisherman's Waders" sign is suggested for this finding, whose recognition may permit the identification of inferior vena cava obstruction in bone scans. The existence of a cavo-portal shunt was also confirmed by dynamic scintigraphy.

Hypertrophic pulmonary osteoarthropathy in nasopharyngeal carcinoma: an early sign of pulmonary metastasis.

The aims of this study were to determine the incidence of hypertrophic pulmonary osteoarthropathy (HPO) in nasopharyngeal carcinoma (NPC) and assess its clinical significance. Altogether, 407 NPC patients were reviewed retrospectively. HPO was identified by 99Tcm-methylene diphosphonate bone scans and related clinical and radiographic evidence. Pulmonary metastases, bony metastases and titre of anti-Epstein Barr virus (EBV) immunoglobulin were assessed in patients with and without HPO. The patients had a mean (+/- S.D.) age of 50.4 +/- 12.4 (range 17-73) years. HPO was found in 27 of the 407 (6.6%) NPC patients, among whom 13 (48%) had pulmonary metastases. HPO preceded lung metastases by 7-22 months (14.4 +/- 6 months) in 7 (52%) patients. Six patients had overt lung metastases at the time of the bone scan. No significant difference was found in anti-EBV immunoglobulins between the patients with or without HPO, nor in the incidence of bony metastases between these two groups of patients. HPO should be regarded as an early sign of pulmonary metastases.

Tc-99m phytate bone marrow scintigraphy showing multiple areas of focal hyperactivity in a patient with lung cancer. A case report.

Focal hyperactivity indicative of metastases is a rare finding in bone marrow imaging. In a lung cancer patient with multiple bony metastases, the Tc-99m phytate bone marrow imaging revealed multiple focal areas of increased radioactivity corresponding to the bone scan findings. The findings presented are consistent with a previous animal study, which found that phytate distribution was similar to that of diphosphonate in the skeletal system of rats and rabbits. The authors conclude that Tc-99m phytate should not be used as a bone marrow imaging agent. Further studies of Tc-99m phytate bone marrow scintigraphy on human beings are under way.

Transvenous permanent left ventricular pacing. A case report.

This case report presents a patient who inadvertently received transvenous permanent left ventricular pacing through an unexpected atrial septal defect. This lead malpositioning was proved by two-dimensional and transesophageal echocardiography. The abnormal pattern of electric activation was demonstrated by radionuclide phase image analysis. He has been followed up for a total of forty-three months with antiplatelet therapy and has been free from systemic embolic phenomena. A simple and readily available method that could lead to early recognition of lead malpositioning is reiterated and the various causes, methods of detection, and prognosis of left ventricular pacing are discussed.

An appraisal of dipyridamole thallium imaging-detected ischemia in Chinese following acute myocardial infarction.

BACKGROUND: The detection of objective myocardial ischemia is an important work-up of risk stratification for survivors of acute myocardial infarction (MI). Intravenous dipyridamole thallium scintigraphy was used to identify the prevalence and prognostic value of silent myocardial ischemia (SI) at the early stage in patients after MI. METHODS: Ninety patients (male/female = 87/3; aged from 36 to 70 years) who succumbed to an episode of MI was recruited in this prospective study. Thallium imaging with reversible or combined defect was defined as presence of SI (Group I), while those with fixed defects or normal images were defined as absence of SI (Group II). Correlation between the patterns of thallium images for postinfarct ischemia and the angiographic lesions was investigated. Also, versatile clinical variables and indexes of adverse cardiac events: unstable angina, CHF, reinfarction, ventricular tachyarrhythmia and sudden death, were evaluated for their influence on patients' prognosis. The average follow-up was 11.6 months. RESULTS: There were 61 patients in the Group I as compared with 29 patients in the Group II. The difference of Killip functional classification between Group I and Group II patients was not significant (1.33 +/- 0.72 versus 1.07 +/- 0.59). Adverse cardiac event occurred in 30% (27/90) of the patients during follow-up. Cardiac death occurred in 6 cases (7%) and were distributed evenly (3 versus 3) in both groups. Group I patients showed a higher number of nonfatal reinfarctions (8 versus 5) and had more cases of percutaneous coronary angioplasty (11 versus 8) than Group II patients. Only two cases in Group I underwent bypass graft surgery. There was no statistic difference among four patterns of thallium image in the cumulative event-free survival curve. Prior history of CHF, prior MI and higher score index of proximal arterial stenosis were the three significant prognostic predictors for late cardiac events. CONCLUSIONS: Dipyridamole thallium imaging-detected SI was frequently seen in the Chinese patients following AMI. It was less valuable than prior histories of CHF, prior MI and higher index of proximal arterial stenosis scores in predicting the short-term unfavorable cardiac events in these patients. A large scale analysis and longer follow-up might be required to more accurately determine the role of this exam for the Chinese victims of myocardial infarction.

Correlation of esophageal manometry and radionuclide esophageal transit in normal subjects.

What was the correlation of esophageal manometry and scintigraphy in Chinese was studied. Thirty-two volunteers (M/F: 18/14, age: 20-57) without evident esophageal motor disturbance and chest deformity underwent manometric measurement in the spine position using a low compliance pneumohydraulic infusion system. These measurements included the location of both upper and lower esophageal sphincter from nostril, and dry or wet swallow elicited peristaltic speed in the lower esophageal segment. Within one week after manometry, they swallowed a technetium-99m colloid bolus to measure radionuclide manifested esophageal transit time in the supine position beneath a gamma-camera. Body heights of enrolled subjects exhibited a significant positive correlation (r = 0.458, p < 0.01) with manometry measured esophageal lengths. Mean radionuclide esophageal transit time was 7.61 +/- 2.51 sec (3.1-13.57 sec). These transit times exhibited a positive correlation with esophageal lengths (r = 0.6, p < 0.001). Radionuclide transit speed was actually slower than either dry swallow or wet swallow elicited speed (p < 0.05). In conclusion, either manometry or scintigraphy manifests their specific benefits to diagnose esophageal motility disorders. Some correlations of measured variables can be obtained if they are simultaneously employed.

Purification of peptide hormones from chinchilla pancreas by chemical assay.

Glucagon was purified from chinchilla pancreas and its biological activity determined. It was isolated using a chemical assay to identify peptides with a histidyl residue at the N-terminus. Chinchilla glucagon has the amino acid sequence HSQGTFTSDYSKHLDSRYAQEFVQWLMNT. It differs from the usual mammalian glucagon by amino acid substitutions at positions 13, 18 and 21 from the N-terminus. Despite these sequence changes, its biological activity is conserved. Chinchilla glucagon has approximately the same potency as pig glucagon in stimulating liver membrane adenyl cyclase activity. Pancreatic polypeptide was also purified from chinchilla pancreas based on its Ala1 signal and has the sequence APLEPVYPGDNATPEQMAQYAAEMRRYINMLTRPRY#.

The differential diagnosis of benign and malignant bony lesions in bone scanning. Using the ratio of radiouptake at different times.

For the evaluation of bony metastases in cancer patients, bone scanning has become an important tool, but some limitations exist. One of these is the differential diagnosis of benign and malignant bony lesions, in which bone scanning shows one or more lesions in the spine. To help solve this, bone scintigraphy was performed 4 and 24 hours after intravenous injection of Tc-99m MDP; the ratio of radiouptake in the lesion and normal spine was measured as 24-hr/4-hr (T/F) ratio. Fifty-four patients with an average age of 56 years were studied and divided into two groups. Group A included 34 patients (17 women and 17 men) with bony metastases. Group B included 20 patients (8 women and 12 men) with radiographically proven benign bony lesions and no evidence of cancer. An LFOV Elscint Apex 400 digital gamma camera and an Informatek Simis 5 nuclear minicomputer were used. The results showed that the T/F ratio of Group A was 1.3 +/- 0.15 (mean +/- SD) and that of Group B was 1.0 +/- 0.12 (mean +/- SD). The P value was less than 0.001. We conclude that the ratio of radiouptake of lesions and normal spine at 24 and 4 hours may be a reliable method of differentiating benign bony lesions from malignant lesions.