Harumi Sakahara

Delayed 18F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography scan for differentiation between malignant and benign lesions in the pancreas

Positron emission tomography (PET) using 18F‐fluoro‐2‐deoxy‐D‐glucose (FDG) has been used for the evaluation of various tumors, but accumulation in inflammatory lesions makes it a controversial modality. The aim of this study was to investigate the usefulness of delayed scanning in differentiation between malignant and benign lesions in the pancreas.

18F-FDG PET in the detection of extrahepatic metastases from hepatocellular carcinoma.

BackgroundPositron emission tomography (PET) with 18F-fluoro-2-deoxy-d-glucose (18F-FDG) is useful in detecting distant metastases from a variety of malignancies. However, its efficiency in detecting distant metastases from hepatocellular carcinoma (HCC) has not been investigated. The aim of this study was to evaluate the usefulness of 18F-FDG PET for the detection of extrahepatic metastases from HCC.MethodsNineteen patients suspected of having extrahepatic HCC underwent 18F-FDG PET. Fourteen patients (group A) had extrahepatic lesions, which were detected by conventional studies. In five patients (group B), conventional imaging showed no extra- or intrahepatic lesions, but the tumor marker levels were elevated. The PET results were compared with those obtained by histopathology or by clinical follow-up.ResultsThe detection rate of 18F-FDG PET was 83% (24 of 29 metastases) for extrahepatic metastases larger than 1 cm in greatest diameter and 13% (1 of 8 metastases) for lesions less than or equal to 1 cm. PET revealed two bone metastases not depicted by bone scan, and detected the nodal metastasis and intestinal metastases inconclusive on computed tomography. Extrahepatic lesions were resected in 5 patients of group A on the basis of PET findings. In all patients of group B, PET results were true negative for extrahepatic metastases, but HCCs were detected in the liver within 4 months in 4 patients. These were no false-positive lesions in either group.ConclusionsThis preliminary study suggested that 18F-FDG PET could provide additional information and contribute to the management of HCC patients suspected of having extrahepatic metastases.

Specificity and Affinity of 26 Monoclonal Antibodies against the CA 125 Antigen: First Report from the ISOBM TD-1 Workshop

The specificity of 26 monoclonal antibodies against the CA 125 antigen was investigated in two phases of the ISOBM TD-1 workshop. The binding specificity was studied using CA 125 immunoextracted by specific antibodies immobilized on various solid phases, or on the surface of human cell lines. Immunometric assays using all possible antibody combinations were used to study the topography of antibody binding sites on the antigen. We conclude that the CA 125 antigen carries only two major antigenic domains, which classifies the antibodies as OC125-like (group A) or M11-like (group B). One antibody, OV 197, showed binding specificity related to some of the OC125-like antibodies, but was classified into a separate group C. The OC125-like group of antibodies has four subgroups with different binding specificities. These are A1 = OC 125 and K 95, A2 = K 93, A3 = B43.13, and A4 = ZS 33, B27.1 and CCD 247. Binding of nonlabelled OC 125 or K 95 to CA 125 caused a marked increase in binding of labelled OV 197 to the complex. This conformational change was not observed with any other antibody combinations. Antibody B43.13 could form immunometric assay combinations particularly with antibodies of subgroup A4, indicating that the B43.13 epitope is in the periphery of the binding area of OC125-like antibodies. The M11-like group of antibodies is more homogenous with strong cross-inhibition between most antibodies. Only one antibody, ZR 38, would form an immunoassay combination with other M11-like antibodies and thus represents a distinct subgroup. The main group of M11-like antibodies are M 11, ZR 45, MA602-6, K 91, OV 185, K 101, K 90, K 96, K 97, K 102, CCD 242, 145-9, and 130-22. Antibody OV 197 binds to a domain designated C and is unique, as stated above. Antibody pairs from any two of the three groups may be used in immunometric assays. Three antibodies were not studied by complete cross-inhibition due to low affinity (OV 198 and K 100) or lack of material (MA602-1). OV 198 and K 100 are most likely OC125-like and MA602-1 is M11-like. Antibody affinity was estimated with labelled antigen in solution or with antigen absorbed on microtiter wells. Western blot analysis showed staining both in the stacking gel and corresponding to a molecule of 200 kDa. There was a marked difference between the antibodies in their ability to bind to CA 125 immobilized on a membrane. Strongest binding was observed with the M11-like antibodies, particularly M 11, K 96, K 97, MA602-6, 145-9. Antibodies belonging to the subgroup A4 were the only OC 125-like antibodies which reacted well with CA 125 in Western analysis. Digestion of CA 125 with proteolytic enzymes showed it to be particularly sensitive to trypsin cleavage. However, no low molecular weight fragments with preserved immunoreactivity were found.

Diffusion-weighted echo planar imaging of ovarian tumors: is it useful to measure apparent diffusion coefficients?

Purpose Our goal was to test the hypothesis, as previously reported in other studies, that apparent diffusion coefficients (ADCs) provide specific information to diagnose ovarian tumors, especially to discriminate between benign and malignant lesions. Method T1-and T2-weighted spin echo imaging and diffusion-weighted echo planar imaging were performed in 31 women with 61 cystic components of ovarian tumors. Results The lesions that showed typical watery intensity, hypointensity in T1-weighted imaging, and hyperintensity in T2-weighted imaging had similar ADCs, ranging from 1.54 to 1.84 × 10−3 mm2 /s. The lesions that showed signal intensity different from typical watery intensity in conventional MRI tended to have low ADCs. In endometrial cysts, the mean ADC of the subgroup that showed typical watery intensity was higher than that of other subgroups. Conclusion With conventional MRI, a tendency of ADCs could be predicted. ADCs may not provide additional information, especially to discriminate benign from malignant lesions.

Avidin–biotin system for delivery of diagnostic agents

Radiolabeled monoclonal antibodies specific for tumor-associated antigens are used for the diagnosis and therapy of malignant tumors. However, the blood clearance of antibodies is slow and tumor-to-nontumor ratios of radioactivity in the current system are not high. To increase tumor-to-nontumor ratios, the concept of pretargeting has been proposed. The strategy is based on the separate administration of the monoclonal antibody and the radiolabel. Because avidin and streptavidin bind to biotin selectively with extremely high affinity, the avidin-biotin system has been applied for pretargeting. With this method, high tumor-to-nontumor ratios are reported, not only in animal experiments, but also in clinical trials. The avidin-biotin system is also used to reduce the background radioactivity of the directly labeled antibody as well as radioimmunoguided surgery.

Reassessment of Diethylenetriaminepentaacetic Acid (DTPA) as a Chelating Agent for Indium-111 Labeling of Polypeptides Using a Newly Synthesized Monoreactive DTPA Derivative

Previous studies on indium-111 (111In) labeling of polypeptides and peptides using cyclic diethylenetriaminepentaacetic dianhydride (cDTPA) as a bifunctional chelating agent (BCA) have indicated that DTPA might be a useful BCA for 111In labeling of polypeptides at high specific activities when DTPA can be incorporated without inducing intra- or intermolecular cross-linking. To investigate this hypothesis, a monoreactive DTPA derivative with a maleimide group as the peptide binding site (MDTPA) was designed and synthesized. A monoclonal antibody (OST7, IgG1) was used as a model polypeptide, and conjugation of MDTPA with OST7, 111In radiolabeling of MDTPA-OST7, and the stability of 111In-MDTPA-OST7 were investigated using cDTPA and benzyl-EDTA derivatives as references. SDS-PAGE analysis demonstrated that while cDTPA induced intramolecular cross-linking, no such undesirable side reactions were observed with MDTPA. MDTPA generated 111In-labeled OST7 with high radiochemical yields at higher specific activities than those produced using cDTPA and benzyl-EDTA derivatives as the BCAs. Incubation of each 111In-labeled OST7 in human serum indicated that MDTPA generated 111In-labeled OST7 of much higher and a little lower stability than those derived from cDTPA and benzyl-EDTA derivatives, respectively. These findings indicated that the low in vivo stability of cDTPA-conjugated antibody reported previously is not attributable to low stability of 111In-DTPA but to formation of intramolecular cross-linking during cDTPA conjugation reactions. The present study also indicated that MDTPA and its precursor, the tetra-tert-butyl derivative of DTPA, would be useful BCAs for 111In radiolabeling of polypeptides that have rapid blood clearance with high specific activities.

Metabolite Alterations in Basal Ganglia Associated with Methamphetamine-related Psychiatric Symptoms: A Proton MRS Study

Following the chronic use of methamphetamine, some individuals experience psychosis and anxiety. One reason may be the persistence of metabolite abnormalities in the brain of currently abstinent former methamphetamine users. In this study, N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr+PCr), and choline-containing compound (Cho) levels were measured in the left and right basal ganglia using proton magnetic resonance spectroscopy (MRS) in 13 abstinent methamphetamine users and 11 healthy comparison subjects with no history of illicit drug use. The methamphetamine users showed a significantly reduced Cr+PCr/Cho ratio in the bilateral basal ganglia compared with the healthy comparison subjects. Furthermore, the reduction in the Cr+PCr/Cho ratio was significantly correlated with the duration of methamphetamine use and with the severity of residual psychiatric symptoms. NAA/Cho ratios in the bilateral basal ganglia did not significantly differ between methamphetamine users and comparison subjects. These findings suggest that protracted use of methamphetamine may cause metabolite alterations in the basal ganglia. Furthermore, residual psychiatric symptoms may be attributable to the metabolite alterations in the basal ganglia.

Contribution of PET in the detection of liver metastases from pancreatic tumours

AIM Although uptake of 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) in the liver is basically high, metastatic liver tumours are known to be positive on positron emission tomography (PET). The purpose of this study is to evaluate the diagnostic accuracy of FDG-PET in detecting hepatic metastases from pancreatic cancer. METHODS Thirty-four patients with histologically proven malignant tumours of the pancreas underwent FDG-PET, computed tomography (CT) and transabdominal ultrasound (US). The findings of PET, CT and US were compared with the histopathologic findings at surgery or with clinical follow-up and the diagnostic accuracy of PET was evaluated. RESULTS PET showed 28 regions of high FDG uptake (SUV = 3.3-9.1) in 13 patients. Twenty-six foci were metastatic lesions confirmed by surgery (n = 11), clinical follow-up (n = 10) or autopsy (n = 5). FDG-PET accurately differentiated seven metastatic lesions from cysts when the diagnosis by US or CT was unreliable because of the small size of the lesion. In two patients who had areas of high uptake in the liver, no metastases were detected by surgery. FDG-PET showed no areas of increased uptake in 21 patients. Surgery revealed no metastatic lesions in the liver in 20 of 21 patients, but a liver metastasis was found at surgery in one patient. The diagnostic accuracy of FDG-PET was 90%, which was comparable with that of US or CT. CONCLUSION Our data suggest that PET is reliable in detecting liver, metastases from pancreatic cancer.

Noninvasive Quantitative Measurements of Regional Cerebral Blood Flow Using Technetium-99m-L,L-ECD SPECT Activated With Acetazolamide: Quantification Analysis by Equal-Volume-Split 99mTc-ECD Consecutive SPECT Method

Resting- and acetazolamide (Acz)-activated-regional cerebral blood flow (rCBF) measurements were performed by consecutive single-photon emission computed tomography (SPECT) studies before and after Acz administration using equal-volume-split technetium-99m-L,L-ethyl cysteinate dimer. Quantitative rCBF images were converted from qualitative axial SPECT images by the application of Patlak plot graphical analysis with radionuclide angiography and Lassens linearization correction. Total time span required for this study was 53 minutes. The unaffected side of 37 studies with unilateral vascular lesions and 45 studies without apparent vascular lesions showed 132 ± 17% and 140 ± 15% increase of mean CBF (mCBF), respectively, under Acz administration. Comparing these values, the Acz-activated rCBF increases of less-affected and affected hemispheres of 23 studies with bilateral vascular lesions (116 ± 13% and 113 ± 12%, respectively) was lower with high statistical significance (P < 0.001). For the other 20 cases, physiologic saline was administered instead of Acz. This group showed no changes in mCBF under placebo administration (after placebo/baseline; 100 ± 6%). Acetazolamide-activated rCBF increase was recognized clearly and easily using quantitative images. This noninvasive method is easy to perform and may be helpful to detect regional abnormalities of hemodynamic reserve in cerebrovascular diseases.

Serum CA 19-9 concentrations and computed tomography findings in patients with pancreatic carcinoma.

Carbohydrate antigen (CA) 19‐9 is a new tumor markerdefined by a monoclonal antibody. Serum CA 19‐9 concentrations and computed tomography (CT) findings were studied in 55 patients with histologically proven adenocarcinomaand in 22 patients with chronic pancreatitis. CA 19‐9 was useful in 83% of cases for the differential diagnosis between pancreatic carcinoma and chronic pancreatitisand serum CA 19‐9 levels in pancreatic carcinoma were highly related to the size of tumors. Serum CA 19‐9 levels greater than 37 U/ml were seen in patients with a tumor of less than 3 cm3 to 5 cmand greater than 5 cm in diameter 13% (1/8)90% (19/21)and 92% (24/26) of casesrespectively. Tumor locationhoweverwas unrelated to serum CA 19‐9 value. These results indicated that the measurement of serum CA 19‐9 concentrations would be useful in mostif not allcases for the differential diagnosis between pancreatic carcinoma and chronic pancreatitisand for the evaluation of tumor burden in patients with pancreatic carcinoma.