Sigma receptors are expressed in human non-small cell lung carcinoma.

N-(2-piperidinoethyl)4-iodobenzamide), IPAB, was used to characterize sigma receptors in non-small cell lung cancer (NSCLC) cell lines. 125IPAB bound with high affinity to large cell carcinoma (NCI-H1299), adenocarcinoma (NCI-H838), and lung carcinoid (NCI-H727) cell lines. Specific IPAB binding was inhibited with high affinity by haloperidol (Ki = 0.6 nM), IPAB (Ki = 14 nM) and 1,3-ditolyl guanidine (DTG) (Ki = 40 nM). Relative to other receptor ligands, IPAB was not readily internalized at 37 degrees C. IPAB had little effect on the growth of NSCLC cells. Scintigraphic imaging studies using 131IPAB in nude mice bearing NCI-H838 xenografts visualized the tumor at 24 or 30 hours after injection. These results suggest that sigma receptors which are present on NSCLC cells may be used as external markers for imaging tumors in vivo.

Preoperative parathyroid localization: prospective evaluation of technetium 99m sestamibi.

The utility of preoperative parathyroid localization remains controversial. The gold standard for identification of abnormal parathyroid glands is exploration of the neck by an experienced surgeon. However, both for the experienced and less experienced surgeon, it may be desirable to localize the abnormality before surgery. Such a study would not only direct the surgeon to the site of the lesion but also would help reduce unnecessary dissection, the number of negative explorations, and operative anesthesia time. Unfortunately, currently used noninvasive techniques including ultrasonography, thallium-technetium subtraction, computed tomography scan, and magnetic resonance imaging have had only limited success (35% to 78%) in demonstrating abnormal parathyroid glands. Thirty patients with proven hyperparathyroidism were enrolled to compare a new imaging agent, technetium 99m sestamibi, as an alternative to thallium 201 for subtraction scintigraphy with technetium 99m pertechnetate. Only 14 of 30 patients operated on at George Washington University underwent an identical surgical approach (exploration of all four glands) and had complete preoperative calcium and parathormone levels, postoperative calcium levels, and total time of surgical procedures to formulate the basis of this report. The remaining 16 had their surgeries at other institutions. A surgical approach different from that used at George Washington University and unavailability of postoperative calcium levels and times of surgical procedures from these institutions necessitated deletion of these 16 patients from this report. Technetium 99m sestamibi-technetium 99m subtraction scans accurately localized the abnormal parathyroid gland in 13 of 14 patients, as compared with only 9 of 14 thallium 201-technetium 99m pertechnetate subtraction scans. These results support technetium 99m sestamibi scanning as the superior modality for preoperative parathyroid localization.

A malignant melanoma imaging agent: synthesis, characterization, in vitro binding and biodistribution of iodine-125-(2-piperidinylaminoethyl)4-iodobenzamide.

In order to develop improved radiopharmaceuticals for imaging malignant melanoma, we have synthesized and characterized 125I-and 131I-labeled (2-piperidinylaminoethyl)4-iodobenzamide (PAB). In vitro binding profiles of IPAB and N-(2-diethylaminoethyl)4-iodobenzamide (IDAB, a structurally related analog of IPAB) for a variety of neurotransmitter receptors suggested that both IPAB and IDAB possessed a high sigma-1 affinity and a low affinity for sigma-2 sites. In vitro homologous competition binding studies of [125I]PAB with human malignant melanoma cell A2058 showed that the tracer was bound to the cells with a high affinity (Ki = 6.0 nM) and that the binding was saturable. Biodistribution studies in nude mice implanted with human malignant melanoma xenografts showed good tumor uptake (3.87% ID/g at 1 hr, 2.91% ID/g at 6 hr and 1.02% ID/g at 24 hr) of [125I]PAB. High tumor-to-nontarget organ ratios were obtained at 24 hr postinjection. Tumor-to-blood, liver, muscle, lung, intestines, heart and brain ratios at 24 hr were 17.80, 3.88, 94.58, 14.29, 10.87, 37.07 and 90.01, respectively. Tumor imaging with [131I]PAB in a nude mice model xenografted with human malignant melanoma at 24 hr clearly delineated the tumor with very little activity in any other organ. These results demonstrate that sigma-1 receptors could be used as external markers for malignant melanoma.

An improved synthesis of [125I]N-(diethylaminoethyl)-4-iodobenzamide: a potential ligand for imaging malignant melanoma.

To improve the radiolabeling yield and the specific activity of [125I]N-(2-diethylaminoethyl)-4-iodobenzamide (DAB), the aryltributyltin precursor was synthesized from the N-(2-diethylaminoethyl)-4-bromobenzamide derivative by palladium catalyzed stannylation using bis(tributyltin). The radiolabeled product, [125I]DAB, was obtained by an iododestannylation reaction in high radiochemical yields (85-94%, radiochemical purity, > 98%) using chloramine-T as an oxidizing agent. The specific activity was greater than 1600 Ci/mmol. The biodistribution studies in nude mice implanted with human malignant melanoma xenograft showed a good tumor uptake (6.14% ID/g at 1 h, 2.81% ID/g at 6 h and 0.42% ID/g at 24 h) of [125I]DAB. Unfortunately, a high uptake in the non-target organs, such as liver and lung, was found. At 1 h post-injection the activity level in liver and lung was 11.76 and 7.58% ID/g, respectively. A slow clearance of activity from liver and lung was observed at 6 h (3.43 and 0.49% ID/g). These results demonstrate that iodinated IDAB is a potential radiopharmaceutical for the management of patients with malignant melanoma.

Reflex sympathetic dystrophy localized to a single digit.

We present 2 patients with reflex sympathetic dystrophy localized to a single digit. Blood flow scintigraphy in 1 patient supported the diagnosis and resolution of the disorder at an early stage. Both patients responded to moderate dose corticosteroid therapy.

Utility of gallium67 scintigraphy and bronchial washings in the diagnosis and treatment of Pneumocystis carinii pneumonia in patients with the acquired immune deficiency syndrome.

Twenty patients with the acquired immune deficiency syndrome (AIDS) and suspected Pneumocystis carinii pneumonia were evaluated by gallium67 (Ga67 scintigraphy and fiberoptic bronchoscopy for initial diagnosis and response to therapy. Lung uptake of Ga67 was demonstrated in 100% of AIDS patients with P. carinii pneumonia, including those with subclinical infection. Fiberoptic bronchoscopy identified P. carinii in the bronchial washings of 100% of cases (19 patients), whereas only 13 of 16 (81%) patients had P. carinii in lung tissue obtained by transbronchial biopsy. Repeat fiberoptic bronchoscopy was performed in 16 of 20 patients. After 2 to 4 wk of therapy, P. carinii was identified in bronchial washings in 8 of 16 (50%) patients and in transbronchial biopsy in 1 of 10 (10%) patients examined. Bronchial washing has a higher yield than transbronchial biopsy in demonstrating P. carinii in patients with AIDS and may evolve as the procedure of choice in such patients. Based on the clinical course and results of Ga67 scintigraphy and fiberoptic bronchoscopy in AIDS patients with P. carinii pneumonia, optimal therapy may require at least 3 wk of treatment.

Exercise radionuclide ventriculographic responses in hypertensive patients with chest pain.

The effectiveness of exercise-treadmill testing in diagnosing coronary-artery disease in hypertensive patients is limited by a high rate of false positivity. Exercise radionuclide ventriculography, however, relies on different criteria (ejection fraction and wall motion), and we have evaluated this procedure in 37 hypertensive and 109 normotensive patients with chest pain, using coronary arteriography as an indicator of coronary disease. In the hypertensive cohort there was no difference in the ejection fraction at rest between the 17 patients with coronary disease and the 20 without it. Neither group had a significant mean (+/- S.E.M.) change in ejection fraction from rest to exercise (-1.9 +/- 2 and - 1.4 +/- 1 per cent, respectively). A wall-motion abnormality developed during exercise in 5 of the 17 hypertensive patients with coronary disease (29 per cent) and in 4 of the 20 without it (20 per cent) (P = not significant). In the normotensive cohort, however, the peak-exercise ejection fractions were significantly different. The 71 patients with coronary disease had a mean decrease of 3.6 +/- 1 per cent, in contrast to the patients without coronary disease, who had an increase of 6 +/- 1 per cent (P less than 0.001). An exercise-induced wall-motion abnormality was seen in 35 of the 71 patients with coronary disease (48 per cent), as compared with 3 of the 38 without it, (8 per cent) (P less than 0.001). We conclude that exercise radionuclide ventriculography is inadequate as a screening test for coronary atherosclerosis in hypertensive patients with chest pain.

Insensitivity of the cold pressor stimulation test for the diagnosis of coronary artery disease.

Cold pressor stimulation (CPS) was compared with supine bicycle exercise during radionuclide ventriculography as a procedure for diagnosing coronary artery disease (CAD). Thirty patients were studied. In the 18 patients with angiographically proved CAD, left ventricular ejection fraction (LVEF) decreased a mean of 5.0 +/- 1.0 ejection fraction units (+/- SEM) in response to CPS. Only two patients developed a new wall motion abnormality. In response to maximal supine exercise, the CAD group showed a mean decrease in LVEF from rest of 1.9 +/- 1.1%. Nine patients developed an exercise-induced wall motion abnormality. In the 12 patients with angiographically proved normal coronary arteries, LVEF decreased a mean of 5.8 +/- 1.3 units in response to CPS and increased a mean of 9.2 +/- 1.2% in response to exercise. Thus, the LVEF response to CPS was not significantly different in the CAD and normal groups (5.0 +/- 1.0 vs 5.8 +/- 1.3, NS). These same patients demonstrated the expected difference in LVEF response to exercise. We conclude that CPS produces similar changes in LVEF in patients with and without CAD, and therefore is not useful in diagnosing ischemic heart disease.

Low-dose heparin for prevention of venous thromboembolism in total hip arthroplasty and surgical repair of hip fractures.

Sixty-seven hip-arthroplasty and fifty-two hip-fracture patients participated in a placebo-controlled randomized double-blind study on the effects of low-dose heparin prophylaxis in the prevention of venous thromboembolism. In this study, a positive thromboembolic event meant a positive test by: (1) daily 125I-fibrinogen scanning, (2) contrast venography on the tenth postoperative day, or (3) radionuclide perfusion lung scan in confirmation of suspected clinical pulmonary emboli. Nineteen (59.4 per cent) of thirty-two placebo-treated arthroplasty patients showed evidence of a thromboembolic event in contrast with eight (22.9 per cent) of thirty-five heparin-treated patients (p less than 0.003). Heparin-treated arthroplasty patients required mean blood transfusions of 4.7 units, contrasted with a mean 3.2-unit transfusion requirement for placebo-treated patients (p less than 0.05). The incidence of observed bleeding complications was higher among the heparin-treated patients. Of the twenty-three placebo-treated patients with fracturs, 39.1 per cent had a thromboembolic event, while 41.4 per cent of the twenty-nine who received heparin showed evidence of thromboembolism, demonstrating that low-dose heparin afforded no protection, nor did it affect the incidence of bleeding complications or transfusion requirements in fracture patients.

Influenza A infection simulating pulmonary embolism.

The diagnosis of pulmonary embolism is generally established when the patient has characteristic pulmonary perfusion abnormalities in the setting of an appropriate clinical history and with no concurrent cardiopulmonary disease on chest x-ray film. The initial evaluation, including positive pulmonary perfusion scan, of four young black women suggested the diagnosis of pulmonary emboli. A syndrome of respiratory tract viral infection then developed, and further evaluation by angiography and perfusion scans contradicted the diagnoses of pulmonary emboli. Each patient had substantial convalescent-phase complement-fixation titers to influenza A. Thus, if reliance is placed in pulmonary perfusion scans, an erroneous diagnosis of pulmonary emboli may be made for patients with influenza A.

Body-background defects with 99mTc-DTPA after renal transplantation: case reports.

Photon-deficient areas adjacent to transplanted kidneys were seen in the early phases of several dynamic studies obtained with 99mTc-diethylenetri-aminepentaacetic acid (99mTc-DTPA). The causes included hematoma, urinoma, and lymphocele. These fluid collections do not readily exchange as part of the extracellular space and, if sufficiently large, may be visualized as photon-deficient areas in the normally homogeneous background of 99mTc-DTPA studies.