Radionuclide lung imaging in respiratory decompression sickness: potential role in the diagnosis and evaluation of hyperbaric therapy.

Of the more than 3.5 million trained divers in the United States, many will experience various illnesses specific to divers. Most of these illnesses are related to the changes in absolute pressure that divers experience while diving. During and after ascent, a diver is at risk for decompression sickness and pulmonary barotrauma. A very rare casualty is pulmonary decompression sickness from immersion. This is a literature review and case report of a young woman with acute respiratory decompression sickness who had defects on perfusion lung imaging after a diving accident and after hyperbaric oxygen therapy. However, the perfusion defects reverted to normal in less than 24 hours. Possible explanations for the changes in the appearances of the scans are offered and discussed. This case report shows the potential utility of lung scanning in the diagnostic examination of these patients and the evaluation of the adequacy of treatment with hyperbaric oxygen therapy. A greater use of ventilation-perfusion lung scans in the treatment of such patients may establish its role more definitely.

Technetium-99m sestamibi uptake in a maxillary brown tumor.

Brown tumors have been reported to take up TI-201 when dual-tracer parathyroid scintigraphy using TI-201 and Tc-99m pertechnetate was performed. With the change to the more favorable Tc-99m sestamibi parathyroid scanning, similar phenomena of tracer uptake in brown tumors have been reported. The authors describe a 44-year-old man with a left maxillary swelling. Laboratory investigations revealed elevated parathyroid hormone levels. Computed tomography of the head showed a left maxillary expansile mass. Subsequently, a Tc-99m sestamibi scan was performed to rule out a parathyroid adenoma. Left inferior parathyroid retention of the tracer was seen, indicating a parathyroid adenoma. An incidental finding was the uptake of Tc-99m MIBI in the left maxillary brown tumor. This case suggests the utility and possible specificity of Tc-99m MIBI uptake in diagnosing brown tumors.

Intussusception secondary to Meckel's diverticulum detection with Tc-99m monoclonal antibodies to granulocytes (Leukoscan).

A case of Meckel's diverticulum causing intussusception in an 8-year-old boy is presented. The Meckel's diverticulum was detected by using a Tc-99m-labeled antigranulocyte monoclonal antibody MN3 (Leukoscan; Immunomedics, Morris Plains, NJ), which is under clinical evaluation for the detection of atypical appendicitis at the authors' institution. Pathologic evaluation confirmed Meckel's diverticulitis with ileal-ileal intussusception.

Indium-111 labeled leukocytes in evaluation of active specific immunotherapy responses.

Active immunization of patients utilizing viral oncolysates (VO) has been studied in clinical trials. VO are extracts of cultured tumor cells that have been infected with certain types of viruses, particularly surface budding varieties. The objectives of the current studies were to examine the trafficking patterns of Indium (In)-111-labeled leukocytes or lymphocytes in two groups of patients with gynecologic malignancies to determine whether these cells migrate to sites of active immunization after VO. Eight patients with ovarian cancer received VO intraperitoneally followed by In-111-labeled leukocytes or lymphocytes (500 &mgr;Ci) intravenously. In a separate trial, three patients with cervical cancer received In-111-labeled lymphocytes after they had been treated with VO administered by the intralymphatic route. Gamma camera imaging was performed to evaluate the distribution patterns of the labeled cells at several time intervals after injection. Results indicate that metastatic tumor sites exposed to VO therapy show significant uptake of In-111 cells. These sites of malignancies were confirmed by computerized tomography and ultrasound scans. In patients with ovarian cancer no uptake of the radiolabeled cells was observed in metastatic tumors of the liver and lymph nodes. In patients with cervical cancer, lymph node metastases exposed to intralymphatic VO therapy were visualized very well. Other known tumor sites not exposed to VO therapy showed no uptake of radioactivity. These findings confirm that VO induces immune responses. This diagnostic nuclear medicine technique may prove to be a useful method for following-up responses to immunotherapy.

Scintigraphic findings of osteomyelitis after intraosseous infusion in a child.

A case of unilateral tibial osteomyelitis in a 20-month-old child after bilateral intraosseous infusion (IOI) needle placement is presented. A review of the indications, potential complications, and scan findings is discussed. This case also shows the lack of significant uptake in the noninfected side, suggesting that a three-phase bone scan is of value in differentiating reactive bone from infected bone in patients with IOI.

Value of single-photon emission-computed tomography in acute stroke therapeutic trials.

BACKGROUND AND PURPOSE: New therapeutic interventions for acute ischemic stroke are aimed at improving cerebral blood flow in the first 3 to 6 hours after symptom onset. Single-photon emission-computed tomography (SPECT) performed in the setting of clinical therapeutic trials may give us a better understanding of the physiological response to new forms of treatment and could impact acute management decisions. METHODS: We prospectively studied 15 patients with hemispheric ischemic stroke with SPECT within 6 hours of symptom onset and again at 24 hours. The ischemic defect was assessed in a semiquantitative manner that used computer-generated regions of interest (SPECT graded scale). This measure was correlated with clinical presentation (National Institutes of Health [NIH] Stroke Scale), initial clinical course (change in NIH Stroke Scale), long-term outcome (Barthel Index at 3 months), and complications of cerebral hemorrhage and edema. RESULTS: The severity of the SPECT graded scale on the admission scan correlated with the severity of neurological deficit (admission NIH Stroke Scale) (P < .05) and was positively associated with poor long-term outcome as measured with the Barthel Index (P < .001) and the complications of cerebral hemorrhage and massive cerebral edema (P < .005). In fact, there was a threshold value for the SPECT graded scale above which all patients suffered poor long-term outcome and the complications of cerebral hemorrhage and edema. CONCLUSIONS: The measurement of an ischemic defect using SPECT is a valid assessment of hemispheric stroke severity in the hyperacute setting and may be useful for selecting or stratifying patients in clinical therapeutic trials.

Should hypertension be treated after acute stroke? A randomized controlled trial using single photon emission computed tomography.

OBJECTIVE: To determine if previously hypertensive patients with acute ischemic stroke should be treated with antihypertensive medication in the immediate poststroke period. DESIGN: Randomized double-blind, placebo-controlled trial. SETTING: Sixteen consecutive hypertensive patients (four men and 12 women; mean age, 66 years [age range, 46 to 83 years]) with middle cerebral artery infarction within 72 hours of onset and blood pressure between 170 and 220 mm Hg(systolic) and 95 and 120 mm Hg (diastolic). INTERVENTION: Placebo (n = 6), nicardipine hydrochloride (20 mg [n = 5]), captopril (12.5 mg [n = 3]), or clonidine hydrochloride (0.1 mg [n = 2]) given every 8 hours for 3 days. MAIN OUTCOME MEASURES: Decline in blood pressure, change in cerebral blood flow as measured by single photon emission computed tomography, and clinical change as determined by the National Institutes of Health Stroke Scale. RESULTS: Blood pressure fell significantly in both the drug-treated group as a whole and in those patients receiving placebo (P < .001). There was no difference in blood pressure levels between these two groups throughout the study period. Patients receiving nicardipine had a consistently lower pressure than the other groups. A significant negative relationship was noted between the maximum blood pressure fall and improvement in cerebral blood flow. There were four patients whose blood pressure dropped by more than 16% of the baseline value on any 24 hours in the first 3 days. All either failed to increase or actually decreased their cerebral blood flow to the affected area. Three of these patients were treated with nicardipine. There was no significant difference in clinical course between the placebo-and drug-treated groups as a whole. CONCLUSIONS: Hypertensive ischemic stroke patients with a moderate elevation of blood pressure in the first few days may not require antihypertensive therapy. Nicardipine and possibly other calcium channel blockers may cause an excessive fall in blood pressure and impair cerebral blood flow in these patients and should therefore be used with caution.

Monoclonal antibody imaging in patients with colorectal cancer and increasing levels of serum carcinoembryonic antigen. Experience with ZCE-025 and IMMU-4 monoclonal antibodies and proposed directions for clinical trials.

In an effort to identify the site of recurrent colorectal cancer in patients with occult metastasis and increasing serum CEA levels, we conducted two trials using monoclonal antibodies (MoAb) against CEA. The first utilized Indium-111-labeled ZCE-025; an immunoglobulin G1 (IgG1) anticarcinoembryonic antigen (anti-CEA) antibody (Hybritech, San Diego, CA). The second study used Tc-99m-labeled Fab' fragment of IMMU-4 (Immunomedics, Morris Plains, NJ). Eighteen patients were imaged with the ZCE-025 and 14 with the Tc-99m Fab' IMMU-4. True-positive scans, defined as at least one correct correlation of the MoAb scan and surgical/histologic findings, were observed in 12 of 15 patients undergoing exploration or biopsy using the ZCE-025 and 11 of 14 using the IMMU-4. There were no true-negative scans with the ZCE-025 and only 2 of 14 with the IMMU-4. There were 3 false-positive scans with the ZCE-025 and 1 of 14 with IMMU-4. There were no false-negative scans with either ZCE-025 or IMMU-4. Four (31%) of 13 patients undergoing exploration and imaged with ZCE-025 and 5 (36%) of 14 imaged with IMMU-4 had complete tumor resection. Treatment decisions were affected in 3 (16%) of 18 ZCE-025-imaged patients and 3 (21%) of 14 IMMU-4 ones. Two (14%) of 14 patients imaged with IMMU-4 had negative MoAb scans and negative laparotomies. Despite these findings, it is not known whether such early detection and resection will translate into improved survival rates. The authors suggest two randomized studies, one designed to ascertain the role of MoAb added to blind exploratory laparotomy. In that study, patients with increasing CEA levels and a negative workup will be randomized to an exploratory laparotomy preceded by MoAb anti-CEA scans or a straight exploratory laparotomy without the assistance of a MoAb anti-CEA scan. Endpoints will be differences in complete resectability and survival. A second study will examine the merits of blind exploratory laparotomies. In that study, patients with increasing CEA levels and a negative workup would be randomized to MoAb imaging, exploratory laparotomy, and radioimmunoguided surgery, and the other cohort of patients would continue to have conventional radiologic workup. Exploration in this latter group would be performed only when indicated by radiologic or endoscopic studies. The endpoint of the study would compare survival in the two cohorts of patients. These two studies may ultimately settle the debate regarding the correct approach to patients with occult metastatic colorectal cancer and a increasing levels of serum CEA.

Ga-67 uptake by metastatic carcinoma of the penis.

Six patients with metastatic carcinoma of the penis underwent Ga-67 citrate scanning. Intense radioactive uptake was noted in the metastatic inguinal lymph nodes that was not influenced by the presence or absence of infection. There was a correlation between clinical improvement and decrease in abnormal groin uptake. The results reported here suggest the possibility of using Ga-67 citrate scanning in the staging, management, and follow-up of this relatively rare condition, although further experience is needed to establish its precise role.

Indium-111-labeled B72.3 monoclonal antibody in the detection and staging of breast cancer: a phase I study.

Sixteen patients with primary breast cancer were studied with a pancarcinoma monoclonal antibody B72.3, an IgG1 molecule directed against tumor-associated glycoprotein (TAG-72) present in several tumors. Five millicuries of 111In was used to label 0.2 mg (six patients), or 2 mg (six patients), or 20 mg using the site-directed bifunctional DTPA method (at carbohydrate moiety). Digital, planar, and SPECT images were obtained at 2, 48, 72 and 96 hr when possible. HAMA levels were obtained before the Mab infusion and at 1, 3, and 6 wk postinfusion. Fourteen of 14 known primary breast lesions were detected by imaging (100% sensitivity). Two fibrocystic lesions were negative. Seven of 14 patients had lymph node metastases by histologic methods, but all were missed by radioimmunoscintigraphy. Tumor uptake of Mab ranged 0.00054%-0.0038% of the ID/g. The tumor-to-normal breast tissue ratio was 4.3 +/- 0.91 (mean +/- s.e.m.). Lymph nodes localization of 111In-B72.3 by tissue analysis was similar for tumor-bearing and normal nodes (0.0039 +/- 0.0023 versus 0.0025 +/- 0.0019). Pharmacokinetics revealed mean plasma half-life of 33.3-41.2 hr for the different doses. There was no statistical difference between any of the pharmacokinetic parameters of different doses. HAMA was positive only in 17% of the patients. The study suggests that this antibody has 100% sensitivity for primary breast cancers, but very poor detection rate of metastatic lesions in axillary lymph nodes; thus making it of questionable value in the initial staging process of this disease.

Quality assurance in a nuclear medicine department.

This article reviews the general principles of quality assurance (QA) in an imaging department, with emphasis on nuclear medicine. The various steps taken during the development of the QA program reflect the response of the QA committee as it came to a better understanding of the components of QA. Accrediting and regulatory bodies have had important roles in providing guidance. Quality control of instrumentation and radiopharmaceuticals opened the gateway to monitoring in high-volume, high-risk areas; however, QA expanded this concept into better generic and clinical monitoring. Encouragement of the use of quality of care referral forms resulted in greater participation by all members of the department. Examples of physicians' QA activities include double reading of images and sending of code cards. Experience with other forms of physician QA activities is also included. The QA committee provides a forum for five steps of QA: identify problems, assess the causes, implement action to prevent them, monitor effects of the actions, and document these activities. These steps should lead to improvement in the standards of patient care.

Imaging with indium111-labeled anticarcinoembryonic antigen monoclonal antibody ZCE-025 of recurrent colorectal or carcinoembryonic antigen-producing cancer in patients with rising serum carcinoembryonic antigen levels and occult metastases.

We tested whether nuclear imaging with indium111 (111In)-labeled murine monoclonal (MoAb) anticarcinoembryonic antigen (anti-CEA) ZCE-025 antibody could detect recurrent disease in patients with a rising serum CEA level but negative findings for computed tomographic (CT) scans of the abdomen and pelvis, chest radiograph, and colonoscopy or barium enema. Twenty patients with a history of completely resected CEA-producing adenocarcinoma (18 with colon cancer, one with breast cancer, and one with Hodgkin's disease) and a rising serum CEA level were given an intravenous infusion of 2 mg of 111In-labeled ZCE-025 mixed with 38 mg of unlabeled ZCE-025. Planar and single-photon emission CT (SPECT) scans were acquired at 72 and 144 hours, and in 19 of the 20 patients these were positive. Of those 19, 13 underwent exploratory surgery, and cancer was found in 10, and two had a diagnostic biopsy, which confirmed cancer. Three patients who had negative laparotomies and all four patients who did not undergo surgery or biopsy were followed radiologically. In all seven, cancer was subsequently detected at the sites suggested by the ZCE-025 scan. Thus, tumor was confirmed in all 19 patients with positive scans. Five of 13 patients who were explored benefited from the study and the exploratory laparotomy, as disease was entirely resected in four or was subjected to definitive radiation therapy to the pelvis in the fifth. In two additional patients who were not explored, MoAb imaging resulted in definitive therapy to regionally confined recurrent disease. 111In-labeled anti-CEA MoAb ZCE-025 scanning in patients with rising CEA successfully imaged metastatic colorectal cancer that eluded detection by other methods and affected the care given to some. These results suggest an important role for 111In-labeled ZCE-025 scanning among patients with rising CEA and otherwise occult metastatic cancer.

Colorectal carcinoma metastases: detection with In-111-labeled monoclonal antibody CCR 086.

A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer.

Role of the gallium scan in Hodgkin's disease.

The reports of 240 gallium scans on 165 patients with Hodgkin's disease were reviewed to compare results with higher doses with those in earlier studies that employed lower doses. Tracer concentrations in specific sites were correlated with radiologic and pathologic reports and with the clinical courses of the patients studied. There were no significant differences in overall results between newer and older gallium scanning techniques. For untreated patients, the overall sensitivity was only 64%, but the overall specificity was 98%. For untreated patients and for patients with relapsing disease, the presence of gallium concentration in a specific site was highly predictive of active Hodgkin's disease at that site. However, for routine follow-up of treated patients, 95% of unsuspected relapses were missed by the scan, indicating the limited usefulness of negative scan results in this setting. For patients with residual abnormalities after therapy, demonstrated by other radiographic means, increased uptake of gallium in abdominal or peripheral lymph nodes also indicated active disease, although lack of uptake was reliable only in the mediastinum. Based on these results, it appears that the higher doses used in this study have not substantially improved the role of gallium scanning in this disease. Although it is potentially useful in providing confirmatory data at diagnosis or in patients with new or residual objective abnormalities after treatment, routine use of gallium scanning in Hodgkin's disease is not recommended.

Role of adrenal imaging in surgical management.

Adrenal imaging using radiopharmaceuticals is a functional test that can contribute significantly to surgical management and follow-up of patients with either benign or malignant conditions of the adrenal cortex and medulla. Imaging of the cortex is achieved by iodine-131-labeled iodomethyl nor-cholesterol (NP-59), while adrenal medulla imaging can be successfully accomplished by 131I-metaiodobenzylguanidine (MIBG), which localizes in the adrenergic nerve terminal with norepinephrine. Both tests carry high sensitivity and specificity for functional tumors and hyperplasia, and often better than CT scanning. This article reviews the current status and clinical utility of nuclear imaging of the adrenal cortex in congenital hyperplasia, low renin hypertension and aldosteronism, and Cushing's syndrome. Adrenal medulla imaging is reviewed in light of our experience at the University of Texas M.D. Anderson Cancer Center in pheochromocytoma, neuroblastoma, and other neuroectodermal tumors. Investigation of 131I-MIBG therapy of metastatic tumors of neuroectodermal origin potentially offers a means of at least controlling symptoms of hormonal secretion in these patients.

Radioimaging of melanoma using 99mTc-labeled Fab fragment reactive with a high molecular weight melanoma antigen.

Twenty patients with metastatic malignant melanoma were studied with 99mTc-labeled monoclonal antibody (MoAb) Fab fragment (NR-Ml-05) reactive with a high molecular weight (Mr 240,000) melanoma associated antigen. Patients received 40 mg unlabeled irrelevant MoAb (NR-2AD-IgG) and 7.5 mg unlabeled NR-Ml-05 (whole IgG) prior to infusion of 10 mg 99mTc-labeled (10-25 mCi) NR-Ml-05 Fab. Unlabeled MoAb were given to block nonspecific and specific binding sites. Gamma camera scans and single photon emission computed tomography were performed at 8 and 24 h postadministration. Of 172 preexisting lesions, 136 were imaged for a sensitivity of detection of 79%. Imaging was site and size dependent with the greatest sensitivity for liver lesions (100%) and the least for bowel (0%). Six sites (2 skin, 1 lung, 3 liver) were detected by single photon emission computed tomography that were missed on routine planar images. Forty-one additional unconfirmed sites were seen. Of these, 7 (17%) have been confirmed as tumor after a median follow-up time of 6 months. False positive scans included scar tissue, areas of chronic inflammation, an infected femoral aneurysm, and septic emboli. Nonspecific uptake of radioactivity occurred in kidney, gallbladder, bowel, thyroid, and myocardium. Human anti-mouse antibodies were detected in up to 69% of patients. In summary, radioimaging with 99mTc-NR-Ml-05 is a sensitive test, especially for detecting liver lesions. It is safe, simple to administer, and convenient for the patient. Biodistribution and imaging sensitivity differ significantly from studies in which 111In-labeled anti-melanoma MoAb have been used.