Adoptive cellular immunotherapy for non-small cell lung cancer: a pilot study.

BACKGROUND: Priming with autologous tumor vaccine followed by ex vivo expansion of activated T cells is a feasible experimental strategy. This paper describes the application of this cellular therapy to treat patients with late-stage non-small-cell lung cancer (NSCLC). METHODS: Twenty-one patients with Stages III and IV NSCLC were treated. Tumor samples were obtained surgically (five patients) or by using aco-axial biopsy needle (16 patients). Each course of vaccination consisted of irradiated tumor cells, mixed with GM-CSF and injected intradermally on Day 1, followed by GM-CSF only on Days 2- 5. The course was repeated 10-14 days later. Lymphocytes were collected 10-14 day after the second course and ex vivo expanded using IL-2 and anti-CD3 Ab. The expansion products were then re-infused into the patients. RESULTS: Twelve out of 16 biopsies resulted in optimal cell numbers for vaccine preparation. Nineteen out of 21 patients achieved a delayed type hypersensitivity (DTH response after two courses of vaccination. In 18/21 patients, the ex vivo expansion products contained > 1.6 x 10(10) cells. Subset analysis showed 77.0-97.2% T cells with a CD4:CD8 ratio of 0.65-4.0; natural killer cells were 2.0-18.6%. There were no significant toxicities. The median survival of all 21 patients was 18.6 months, with a 1-year survival of 51.6%. CONCLUSION: Autologous tumor cell-vaccination may be combined with ex vivo expansion of lymphocytes as adoptive cellular immunotherapy for advanced NSCLC. Overall survival in this cohort of poor prognosis patients compared favorably with results reported in the literature.

Radiolabeled MDA2, an oxidation-specific, monoclonal antibody, identifies native atherosclerotic lesions in vivo.

BACKGROUND: Oxidatively modified low-density lipoprotein (LDL) is present in atherosclerotic but not normal arteries and plays a crucial role in the pathogenesis and adverse consequences of atherosclerotic lesions. We previously generated a series of monoclonal antibodies (MoAb) against oxidation-specific neo-epitopes formed during the oxidative modification of LDL. MDA2, a prototype MoAb, recognizes malondialdehyde-lysine epitopes (eg, in malondi-aldehyde-modified LDL) within atherosclerotic lesions. We describe the in vivo characteristics of MDA2 and initial noninvasive imaging studies of atherosclerosis in rabbits. METHODS: To assess the in vivo specificity of MDA2 for atherosclerotic lesions, iodine 125-MDA2 was intravenously injected into 7 LDL-receptor deficient Watanabe heritable hyperlipidemic (WHHL) and 2 normal New Zealand white (NZW) rabbits, and the aortic plaque uptake was evaluated 24 hours later. 125I-Halb, an isotype-matched irrelevant MoAb that binds to human albumin, was injected into 5 WHHL and 2 NZW rabbits as a control. Aortic autoradiography was performed, and the mean uptake of MoAbs was measured as the percent injected dose per gram aortic tissue. Gamma camera imaging was then carried out in 7 WHHL rabbits and 2 NZW rabbits with 99mTc-MDA2. Imaging was carried out at 10 minutes and at 12 or 24 hours. Malondialdehyde-LDL was then injected to clear the blood pool signal, and final images were obtained 2 hours later. RESULTS: Mean uptake of 125I-MDA2 in the entire aorta was 17.4-fold higher in WHHL than in NZW aortas (P < .001), and 2.8-fold higher than 125I-Halb in WHHL aortas. 125I-MDA2 also had higher specificity for lesioned areas than 125I-Halb (plaque/normal ratio 6.3 vs 2.9, P < .001). Autoradiograph of aortas of 125I-MDA2-injected WHHL rabbits revealed uptake in lipid-stained lesions with absence of signal in adjacent normal arterial tissue. Immunostaining of WHHL lesions, which accumulated MDA2 as noted on autoradiography, revealed that uptake was highest in areas with abundant foam cells and in lipid-rich necrotic core areas. Autoradiograph of aortas from NZW rabbits injected with 125I-MDA2 did not yield any visible signal. Planar gamma camera in vivo scintigraphy revealed a visible signal in 4/7 WHHL rabbits, which was confirmed by aortic Sudan staining. CONCLUSION: Radiolabeled MDA2 shows excellent in vivo uptake and specificity for atherosclerotic lesions containing abundant oxidation-specific epitopes. The in vivo imaging studies suggest that noninvasive imaging of oxidation-rich atherosclerotic lesions with radiolabeled MDA2 may be feasible in human beings with optimization of the imaging methods.

Reduction in cortical IMP-SPET tracer uptake with recent cigarette consumption in a young group of healthy males. San Diego HIV Neurobehavioral Research Center.

Functional brain imaging techniques are being used increasingly to infer disturbances in brain function in various neuropsychiatric disorders, but the specificity of such findings is not always clear. We retrospectively examined the effects of one possible confound - cigarette smoking - on cortical uptake of iodine-123 iodoamphetamine (IMP) using single-photon emission tomographic imaging in a young (mean age=35 years) healthy group of male controls divided according to their smoking history. Subjects who had never smoked (n=17), or those with a history of smoking but no recent smoking (n=8), had equivalent and significantly higher mean cortical uptake of IMP than subjects with a history of smoking and who were current smokers (n=8). There were no differences in the cortical distribution of IMP. Our results indicate that cigarette smoking has an acute effect on global cerebral blood flow. This potential confound must be considered before abnormalities in cortical tracer uptake are attributed to some neuropsychiatric disorder of interest.

Chronic pulmonary thromboembolism: detection of regional hypoperfusion with CT.

PURPOSE: To study the relationship of regional hypoperfusion and areas of decreased lung attenuation on computed tomographic (CT) scans of patients with chronic pulmonary thromboembolism. MATERIALS AND METHODS: Preoperative CT scans of five patients (four men and one woman, aged 29-72 years) with chronic pulmonary thromboembolism were reviewed and compared with axial single photon emission CT (SPECT) perfusion scans obtained at similar levels. Regions of varying attenuation and perfusion were scored on a three-point scale. RESULTS: In the five patients, 198 regions were identified. Of 176 abnormal regions at SPECT, 133 were abnormal at CT (sensitivity, 75.6%). Eleven of 22 regions interpreted as normal at SPECT were judged to have normal attenuation at CT (specificity, 50%). The overall accuracy of CT for detecting areas of hypoperfusion was 72.7% (P = .011). CONCLUSION: A mosaic pattern of lung attenuation at CT is a sign of variable regional perfusion and may suggest chronic pulmonary thromboembolism as a cause for pulmonary hypertension.

Technetium-99m labeled micro aerosol "Pertechnegas". A new agent for ventilation imaging in suspected pulmonary emboli.

In this preliminary study, four patients suspected of having pulmonary emboli underwent ventilation imaging after inhaling approximately 1 mCi (37 MBq) of Tc-99m Pertechnegas (micro aerosol carbon particles labeled with Tc-99m) in five breaths or less. Planar images in multiple projections were recorded for preset counts. A final posterior image was acquired to evaluate residual lung background activity. Immediately following ventilation imaging, perfusion imaging in the identical projections was performed using 4 mCi (148 MBq) of Tc-99m MAA. Two of the four patients demonstrated matched uniform ventilation and perfusion and two showed segmental ventilation-perfusion "mismatched" defects consistent with pulmonary emboli. In each case, residual Pertechnegas background lung activity (count rate) at the end of the last ventilation image was less than 10% of the initial Tc-99m MAA counts (count rate). The advantages of Pertechnegas, in comparison to aerosolized DTPA, include: less residual ventilation image activity superimposed on the MAA perfusion images, reduced demand for patient cooperation due to fewer required breaths (five or less), and lack of deposition of activity in the central airways. The authors conclude that Pertechnegas has properties that make it ideally suited for routine lung ventilation imaging.

Improvement of exercise capacity after nifedipine in patients with Eisenmenger syndrome complicating ventricular septal defect.

We investigated the potential benefit of a preferential pulmonary vasodilatory effect of nifedipine in 4 patients with Eisenmenger syndrome complicating ventricular septal defect. First-pass radionuclide scan was performed at rest to measure intracardiac shunting before and after nifedipine. Two hours after 20 mg sublingual nifedipine, right-to-left shunt increased from 16.3 +/- 1.4 to 20.4 +/- 1.5% (p less than 0.05), but systemic arterial oxygen saturation (SAO2) remained steady. With 4 weeks of maintenance nifedipine therapy, resting intracardiac shunting and SAO2 were unchanged from baseline. Symptom-limited cycle ergometry was performed before and after maintenance nifedipine with placebo control. Exercise duration was prolonged (8.7 +/- 0.6 vs. 6.8 +/- 0.9 min; p less than 0.02) and SAO2 at each stage of exercise was consistently increased in all patients after nifedipine. Cardiac output and the SAO2 at peak exercise were similar. Thus, chronic nifedipine therapy increases SAO2 on exercise and improves maximal exercise capacity in patients with Eisenmenger syndrome, which is not predicted by study of resting intracardiac shunting after acute therapy.

Role of bone scanning in detection of subclinical bone metastasis in nasopharyngeal carcinoma.

One hundred thirty-two new patients with nasopharyngeal carcinoma and no evidence of distant metastases were evaluated for bone metastases with bone scanning. Forty-four patients had abnormal hypercaptation. These abnormal findings were considered related to benign diseases in 39 patients after correlating clinical examinations and skeletal radiographs. The remaining five patients had positive bone scanning which was suggestive of bone metastasis. There were 13 patients who developed symptomatic bone metastases over a follow-up period of 0.2-41 months. In three of these, the bone metastases corresponded to the sites of abnormal hypercaptation in the initial positive bone scanning. In view of the low sensitivity and specificity of bone scanning in this setting, routine bone scanning for staging nasopharyngeal carcinoma is not recommended. But in the research setting, baseline scanning is useful to make subsequent scanning more valuable, and it reduces false-positive results.

Hypocalcemic heart failure in end-stage renal disease.

A 37-year-old woman presented with hypocalcemic heart failure complicating end-stage renal disease. Heart failure persisted despite conventional therapy but improved after correction of hypocalcemia. Continuous monitoring of left ventricular function by radionuclide study during calcium replacement showed dramatic improvement. Our case showed that hypocalcemia could be a rare but reversible cause of frank heart failure in uremic patients.

Pediatric pyeloplasty: 50 patients with 59 hydronephrotic kidneys.

A report of 59 hydronephrotic kidneys due to pelviureteric junction (PUJ) obstruction in 50 children less than 12 years of age is presented. Thirty-two percent of the patients were less than 1 year of age, with their main presenting feature being an abdominal mass (88%). For older children, loin or abdominal pain was the chief presenting symptom (68%). During infancy, the left and right sides were equally affected, followed closely by bilateral involvement. On the other hand, in older children, the left side was predominantly affected, being twice as common as the right, and the latter again was twice as common as bilateral involvement. Dismembered pyeloplasty was the procedure used in most cases (88%); the nephrectomy rate was 8% for grossly dilated or dysplastic kidneys. During follow-up (of 6 months to 10 years) of 54 pyeloplasties, improvement was seen in 36 (67%), 12 were unchanged (22%), and one reverted to normal (2%) after the initial operation. Two (4%) worsened initially but achieved stabilization after reoperation; the remaining 3 patients (6%) showed unsatisfactory results. Stents were used in 65% of the cases and nephrostomies in 53%.

Subcortical arteriosclerotic encephalopathy: a clinical and radionuclide brain scintiscan study.

Thirty Chinese patients with clinical and computed tomographic (CT) features of subcortical arteriosclerotic encephalopathy (SAE) were reviewed. It is concluded that the features were sufficiently characteristic for SAE to be considered as a sub-category of cerebrovascular disease and an identifiable cause of dementia in the elderly. Sixteen patients in this series underwent radioisotope brain scintiscan, in which the dynamic radionuclide scintiangiography (RSA) correlated with the clinical course. An increased mean plateau/peak value in the hemispheric curves is seen in the deteriorating patients in contrast to the stable patients.