A 72-year-old patient with type 2 diabetes mellitus underwent F-FDG PET/CT for diabetic foot infection. No increased focal uptake was seen. F-FDG uptake was absent in the second, third, and fourth ...toes of the right foot. Angiography demonstrated severe stenosis in the proximal anterior tibial artery and segmental stenosis on the posterior tibial artery. The patient was diagnosed as having dry gangrene of the second to fourth toes of the right foot due to ischemia. He underwent a selective amputation because of the lack of revascularization possibilities.
We have previously shown that, in vitro, monoclonal antibodies (mAbs) labeled with the Auger electron emitter (125)I are more cytotoxic if they remain at the cell surface and do not internalize in ...the cytoplasm. Here, we assessed the in vivo biologic efficiency of internalizing and noninternalizing (125)I-labeled mAbs for the treatment of small solid tumors.
Swiss nude mice bearing intraperitoneal tumor cell xenografts were injected with 37 MBq (370 MBq/mg) of internalizing (anti-HER1) (125)I-m225 or noninternalizing (anti-CEA) (125)I-35A7 mAbs at days 4 and 7 after tumor cell grafting. Nonspecific toxicity was assessed using the irrelevant (125)I-PX mAb, and untreated controls were injected with NaCl. Tumor growth was followed by bioluminescence imaging. Mice were sacrificed when the bioluminescence signal reached 4.5 x 10(7) photons/s. Biodistribution analysis was performed to determine the activity contained in healthy organs and tumor nodules, and total cumulative decays were calculated. These values were used to calculate the irradiation dose by the MIRD formalism.
Median survival (MS) was 19 d in the NaCl-treated group. Similar values were obtained in mice treated with unlabeled PX (MS, 24 d) and 35A7 (MS, 24 d) or with (125)I-PX mAbs (MS, 17 d). Conversely, mice treated with unlabeled or labeled internalizing m225 mAb (MS, 76 and 77 d, respectively) and mice injected with (125)I-35A7 mAb (MS, 59 d) showed a significant increase in survival. Irradiation doses were comparable in all healthy organs, independently from the mAb used, whereas in tumors the irradiation dose was 7.4-fold higher with (125)I-labeled noninternalizing than with internalizing mAbs. This discrepancy might be due to iodotyrosine moiety release occurring during the catabolism of internalizing mAbs associated with high turnover rate.
This study indicates that (125)I-labeled noninternalizing mAbs could be suitable for radioimmunotherapy of small solid tumors and that the use of internalizing mAbs should not be considered as a requirement for the success of treatments with (125)I Auger electrons.
This study sought to investigate whether the presence of right ventricular systolic dysfunction with pre‐existing left ventricular systolic dysfunction is associated with higher plasma brain ...natriuretic peptide (BNP) levels, compared with patients with isolated left ventricular dysfunction. Eighty‐five patients referred for evaluation of isotopic ventricular function were prospectively included in the study. Left (LVEF) and right (RVEF) ventricular ejection fractions were evaluated by gated blood pool scintigraphy and compared with plasma BNP levels. BNP correlated negatively with LVEF, except in patients with ischaemic heart disease (P=0.09) and in patients with LVEF<40% (P=0.11). In contrast, BNP levels correlated negatively with RVEF for all subgroups. Among patients with RVEF<40%, no significant BNP difference was found between patients with or without additional left ventricular systolic dysfunction (P=0.51). Among patients with LVEF<40%, plasma BNP levels were significantly higher in patients with RVEF<40% than in patients with RVEF≥40% (P=0.004) whereas age, renal function, clinical findings, ventricular volumes, LVEF or medication were not significantly different. In conclusion, an important increase in BNP levels in patients with left ventricular systolic dysfunction should be considered by cardiologists as an indication of high risk of right ventricular dysfunction and should justify further investigation.
Primary progressive aphasia (PPA) is rare. Only limited series have been reported with SPECT or PET. Moreover, in the majority of studies, the left-to-right asymmetry ratio was used, leading to ...difficulties in right hemisphere analyzes.
Twenty-nine patients with clinical criteria of PPA (Mesulam and Weintraub) were included and compared with 12 control subjects. Complete language examination was performed in all patients. SPECT was performed on a double-head gamma camera after intravenous injection of hexamethylpropyleneamine oxime (22 patients and 12 control subjects) or ethylcysteinate dimer (7 patients). Nineteen regions of interest (ROIs) were drawn on each hemisphere in all patients using the Talairach atlas. The perfusion index (PI = cortex-to-cerebellum ratio) was calculated for each ROI. Atrophy was quantified on MRI by consensus of 3 observers in 16 cortical ROIs. ANOVAs were used to compare the PI between (a). patients and control subjects, (b). patients with (n = 15) or without (n = 14) lexicosemantic abnormalities (LS+ vs. LS-) and patients with (n = 19) or without (n = 10) arthric disorders (A+ vs. A-), and (c). patients with or without atrophy.
In the 29 patients, the PI was significantly lower in the left temporopolar, left lateral temporal, left Wernicke, left parietal, and right lateral temporal cortex when compared with control subjects (P < 0.001). In LS+ patients versus control subjects, the PI significantly decreased in the left temporal cortex (lateral temporal; medial temporal; temporopolar; Wernicke), left Broca, left parietal, and right lateral temporal cortex (P < 0.001). In addition, LS+ versus LS- comparison showed a significant decrease in the left lateral, left medial temporal, and left Broca cortex (P < 0.001). In comparison with control subjects, the PI was not significantly different in A+ patients, whereas in A- patients the PI was significantly decreased in the left and right lateral temporal cortex, left Wernicke, and left parietal cortex. Moreover, the PI significantly decreased in the left lateral temporal region in A+ patients compared with A- patients. Finally, in patients without atrophy, the PI significantly decreased in the right and left lateral temporal cortex and the left parietal cortex (P < 0.01).
Our study demonstrates that right-handed patients with PPA present a decreased perfusion in the bilateral temporal cortex. Moreover, in these regions, morphologic abnormalities are preceded by perfusion abnormalities. Finally, our results show that large left temporal dysfunction occurs in patients with LS disorders.
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