Improved staging of B-cell non-Hodgkin's lymphoma patients with 99mTc-labeled LL2 monoclonal antibody fragment.

Radioimmunodetection (RAID) with the 99mTc-labeled Fab' fragment of monoclonal antibody (MoAb) LL2 has been reported to have a high lesion detection rate for malignant lymph nodes as well as for visceral and skeletal tumor masses (20). Our purpose in this study was to evaluate the safety and staging efficacy of the 99mTc-labeled Fab' fragment of MoAb LL2 in patients with various grades and stages of B-cell non-Hodgkin's lymphoma (NHL). Thirty adult patients, 13 male and 17 female, ranging in age from 20 to 80 years, with at least one biopsy-proved malignant node (> or = 0.5 cm) and a Karnofsky performance score of > or = 60% were enrolled in this study. Patients underwent selected planar and single photon emission computed tomographic imaging at 6 and 18 h after receiving an i.v. infusion of 0.25-1 mg of LL2 Fab' fragment labeled with 25-30 mCi of 99mTc. RAID findings were compared with physical examination, chest radiography, computed tomography, magnetic resonance imaging, and bone and 67Ga scan findings. The RAID scan was positive in all but three patients. The sensitivity for known lesions was 90% and for suspected lesions, 89%, with an overall positive predictive value of 96%. Twenty-nine of the 30 patients had either low- or intermediate-grade NHL. Fifteen of 16 (94%) low-grade patients were correctly staged by RAID; three of these patients were correctly upstaged. Twelve of the 13 (92%) intermediate-grade patients were correctly staged by RAID; two of these patients were correctly upstaged. The high-grade NHL patient was staged correctly by RAID. Infused doses of 99mTc-labeled LL2 Fab' of 0.5 and 1.0 mg did not affect lesion sensitivity. The RAID sensitivity decreased as the total tumor burden increased > or = 100 g. On the basis of these initial results, the 99mTc-labeled Fab' fragment of MoAb LL2 (LymphoScan) seems to yield useful clinical information, especially for the staging of B-cell NHL patients who do not have bulky disease (i.e., tumor burdens of < or = 100 g).

Role of technetium 99m-labeled monoclonal antibody in the management of melanoma patients.

PURPOSE: A study was performed to assess the usefulness of a radiolabeled monoclonal antibody (MoAb; technetium 99m NR-ML-05 Fab) as a detecting agent, as well as to evaluate its role in the overall decision-making process in the management of cutaneous malignant melanoma. PATIENTS AND METHODS: Twelve patients with histologically confirmed primary cutaneous melanoma and palpable regional nodes were injected with MoAb NR-ML-05 Fab, radiolabeled with 20 to 30 mCi of 99mTc. Whole-body anterior and posterior images were obtained. Left and right lateral views of the head and anterior and posterior views of the chest, abdomen, pelvis, and extremities were obtained, as were selected single-photon emission computed tomographic (SPECT) views of regional lymph nodes and areas of known or suspected lesions. RESULTS: In nine of 12 patients, clinical and/or MoAb evolution identified 30 discrete sites of suspected melanoma. The remaining three patients showed no positive sites, and there was no evidence of metastatic melanoma. All 30 sites were examined microscopically, and melanoma was confirmed histologically in 23. The remaining seven were negative. MoAb imaging detected 21 (true-positive) but failed to detect two (false-negative) lesions. Sensitivity was 91% (21 of 23); positive predictive value was 95% (21 to 22). CONCLUSIONS: MoAb imaging seems to provide an excellent way to obtain information with regard to the metastatic status of melanoma patients. Immunocytochemistry showed that MoAb (NR-ML-05) is as sensitive as the S-100 antibody and probably more sensitive than the commercially available antimelanoma antibody HMB-45.

Radioimmunoscintigraphy in patients with early stage cutaneous malignant melanoma.

UNLABELLED: CT and MRI examinations remain relatively insensitive for the detection of metastatic melanoma lesions, especially those of regional lymph nodes. Imaging cutaneous malignant melanoma patients with the Fab fragment of monoclonal antibody (MAb) NR-ML-05 labeled with 99mTc has been reported to increase the accuracy of staging. Our purpose in this study was to assess the sensitivity of 99mTc-labeled NR-ML-05 in detecting the spread of melanoma. METHODS: Twenty-six adult cutaneous malignant melanoma patients were enrolled in this study and were followed for 6 to 60 mo after radioimmunoscintigraphy. At the time of imaging, 20 patients had their primary lesions resected, whereas the remaining 6 patients had their primary lesions intact. RESULTS: Radioimmunoscintigraphy correctly detected 8 of 18 suspicious lesions as malignant, as well as 4 additional malignant lesions which had not been suspected previously. Radioimmunoscintigraphy also correctly identified 8 of the 18 suspicious lesions as benign. Two of the 18 suspicious lesions were found to be false negatives. The overall lesion sensitivity of radioimmunoscintigraphy was 86%. CONCLUSION: Twenty-four of the 26 patients were correctly staged by radioimmunoscintigraphy. The accuracy of staging of cutaneous malignant melanoma patients by clinical and or radiologic examinations (73%) was greatly improved with the use of radioimmunoscintigraphy (93%). These results suggest that radioimmunoscintigraphy may be a clinically useful adjunct to the current armamentarium for guidance of medical, and particularly surgical, therapy of cutaneous malignant melanoma patients.

Using vascular structure for CT-SPECT registration in the pelvis.

UNLABELLED: The authors outline a method for three-dimensional registration of pelvic CT and 111In-labeled monoclonal antibody capromab pendetide (111In MoAb 7E11.C5) images using 99mTc-labeled red blood cell SPECT data. METHODS: This method of CT-SPECT registration relies on the identification of major blood vessels in the CT and 99mTc SPECT images. The vessels are segmented from the image datasets by outlining them on transverse planar slices using a mouse-based drawing tool. Stacking the transverse outlines provides a three-dimensional representation of the vascular structures. Registration is performed by matching the surfaces of the segmented volumes. Dual isotope acquisition of 111In and 99mTc activities provides precise SPECT-SPECT registration so that registration in three dimensions of the 111In MoAb and CT images is achieved by applying the same transformation obtained from the 99mTc SPECT-CT registration. RESULTS: This method provided accurate registration of pelvic structures and significantly improved interpretation of 111In MoAb 7E11.C5 exams. Furthermore, sites of involvement by prostate cancer suggested by the 111In MoAb examination could be interpreted with the bony and soft tissue (nodal) anatomy seen on CT. CONCLUSION: This method is a general clinical tool for the registration of pelvic CT and SPECT imaging data. There are immediate applications in conformal radiation therapy treatment planning for certain prostate cancer patients.

Localization of pulmonary human sarcoma xenografts in athymic nude mice with indium-111-labeled monoclonal antibodies.

In order to study localization of metastatic tumors with a radiolabeled monoclonal antibody, a pulmonary metastases model was devised in athymic mice. Metastatic pulmonary sarcoma colonies were verified by histological examination. A murine monoclonal antibody (MAb 19-24) directed against a human sarcoma antigen was labeled with indium-111 (111In) by use of the linker 1-(p-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid (SCN-Bz-DTPA). MAb P3 was similarly labeled as a negative control. In the group given MAb 19-24, the percent injected dose per gram lung tissue bearing tumor colonies (30.1%, 29.6%, and 27.7% on Days 1, 2, and 3, respectively) was significantly (p less than 0.05) higher than in those receiving MAb P3. Hepatic activities of both 111In-MAb 19-24 and 111In-MAb P3 were low. The lungs with tumor colonies demonstrated clearest images on Day 3. The specific binding of 111In-SCN-Bz-DTPA-labeled MAb 19-24 to pulmonary xenografts without appreciable liver uptake indicates that it may be useful in the clinical localization of pulmonic metastatic lesions.

Improved sarcoma imaging and reduced hepatic activity with indium-111-SCN-Bz-DTPA linked to MoAb 19-24.

A murine monoclonal antibody (MoAb 19-24) directed against a human sarcoma antigen was prepared and labeled with 111In by use of the linker 1-(p-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid (SCN-Bz-DTPA). Imaging and biodistribution of this radioimmunocomplex were evaluated. MoAb P3 was similarly labeled as a negative control. Of 24 athymic mice bearing s.c. human fibrosarcoma, 12 received 10 microCi of [111In]MoAb 19-24 and 12 received 10 microCi of [111In]MoAb P3. The mice were imaged at 24, 48, 68, or 168 hr, after i.p. injection. Region of interest and biodistribution analysis showed maximum localization of MoAb 19-24 in the tumor at 72 hr with maximum liver localization of 24 hr. Analysis of MoAb P3 showed maximum tumor and liver activity at 24 hr. Tumor specificity studies were also conducted in three nude mice bearing a sarcoma in the left flank and a Burkitt's lymphoma in the right flank. Selective uptake was seen in the sarcoma but not in the lymphoma. The excellent uptake of [111In]SCN-Bz-DTPA-MoAb 19-24 in sarcoma without appreciable liver activity indicates that it may be a useful tumor imaging agent in man.

Staging non-small cell carcinoma of the lung using technetium-99m-labeled monoclonal antibodies.

A technetium-labeled monoclonal antibody was administered to 52 patients with non-small cell lung carcinoma, either to stage the mediastinum preoperatively or to detect distant metastases. Results from planar and tomographic imaging are compared to CT and histologic confirmation. Differences in detection rates and predictive values between imaging modalities are discussed. The authors conclude that imaging with a technetium-labeled monoclonal antibody is safe and accurate and may be useful for staging patients with either operable or inoperable non-small cell lung cancer.

The use of intravenous dipyridamole in thallium 201 myocardial perfusion imaging.

Thallium 201 myocardial perfusion imaging is a standard method of evaluating regional myocardial blood flow. Myocardial perfusion is best evaluated at rest and during exercise, however, alternative methods have been sought to increase coronary blood flow in patients incapable of performing adequate exercise. A promising new method is the use of intravenous dipyridamole for pharmacologic stress imaging. It has distinct advantages over traditional treadmill exercise testing. The primary advantage of combining intravenous dipyridamole and thallium 201 is for testing patients in whom exercise is impractical or contraindicated. Examples include patients taking beta blockers and those who have had myocardial infarction or have severe peripheral vascular disease. To date, this agent has been available only to clinical investigators in approved protocols. With continued success, it should be approved for general use in the near future.

A strategy for Compton scatter correction in brain SPECT by orthogonal image expansions assisted by neural networks.

The simultaneous dual energy acquisition is often required to accurate co-registration of brain images of both energy windows. However, the reconstructed images in the lower energy window are usually distorted by a significant Compton scatter component originating from the higher energy photons. We are proposing two methods for calculating the Compton scatter correction. Both of them utilize sets of TC99m and associated Compton scatter images in TI(201) energy window that represent a patient population and calculate the sought Compton image estimate 'by comparison' of the given new Tc99m image with the Tc99m set. The first method is based on the principal component image expansion and the second one utilizes in addition learning neural networks. Means to measure the accuracy of results are proposed as well. The proposed methods can be modified for application to other anatomical domains.

Brain SPECT imaging and treatment with IVIg in acute post-infectious cerebellar ataxia: case report.

A 19 year-old man presented with pharyngitis and cervical lymphadenopathy, followed by vomiting and acute cerebellar ataxia. Serologic studies were consistent with a recent Epstein-Barr virus infection. Although contrast-enhanced brain computed tomography and MRI scans were normal, brain perfusion single photon emission tomography (SPECT) examination using 99mTc-HMPAO, performed on the 15th day of illness, showed marked cerebellar hyperperfusion, suggesting a diagnosis of acute post-infectious cerebellitis. After treatment with intravenous human immunoglobulin (IVIg, 2 g kg-1 over three days), progressive neurologic improvement occurred over two weeks. A brain SPECT study repeated after two additional weeks demonstrated a normal perfusion pattern. We conclude that brain perfusion SPECT examination is useful in identifying post-infectious cerebellitis and in monitoring its clinical course. In addition, IVIg may be helpful in treating this condition.

Compton scatter correction in case of multiple crosstalks in SPECT imaging.

A strategy for Compton scatter correction in brain SPECT images was proposed recently. It assumes that two radioisotopes are used and that a significant portion of photons of one radioisotope (for example, Tc99m) spills over into the low energy acquisition window of the other radioisotope (for example, Tl201). We are extending this approach to cases of several radioisotopes with mutual, multiple and significant photon spillover. In the example above, one may correct not only the Tl201 image but also the Tc99m image corrupted by the Compton scatter originating from the small component of high energy Tl201 photons. The proposed extension is applicable to other anatomical domains (cardiac imaging).

Preoperative imaging in primary hyperparathyroidism. Role of thallium-technetium subtraction scintigraphy.

Primary hyperparathyroidism, although often silent clinically, may lead to significant morbidity if it remains untreated. In more than 95% of all cases the cause is a parathyroid adenoma or glandular hyperplasia. Regression of disease follows successful surgical excision of the abnormal parathyroid gland. Recurrent or persistent hyperparathyroidism is most commonly caused by solitary adenomas, which may have an ectopic location. Preoperative localization of lesions may improve postoperative cure rates and decrease morbidity. Thallium T1 201 chloride-technetium Tc 99m pertechnetate subtraction scintigraphy was performed on 15 patients with primary hyperparathyroidism. The sensitivity and specificity for detection of abnormal glands were 90% and 95%, respectively. False-positive or false-negative results were minimize by strict adherence to a protocol and by the use of well-defined diagnostic criteria. Because of the superior sensitivity and specificity, this modality should be the primary imaging method of choice for preoperative evaluation of primary hyperparathyroidism. The relative role of other imaging modalities is also discussed.

Pitfalls in diagnosing brain death in infancy.

A 3-year-old child with phenotypic trisomy 18 syndrome survived 26 days after a cardiopulmonary arrest, secondary to an acute viral illness. The child was deeply comatose. No barbiturates, other sedatives, or aminoglycoside antibiotics had been recently administered. The child was normothermic with adequate cardiovascular function. Brain stem function was absent, as assessed by testing of brain stem reflexes. Serial cerebral radionuclide angiograms (CRAG) documented intact cerebral blood flow while electrocerebral silence (ECS) was present on two consecutive EEG recordings within 24 hours. Preservation of intracranial circulation was confirmed by rapid rotational computed tomographic (CT) scans. Cranial CT scans also revealed communicating hydrocephalus, and bilateral basal ganglia hemorrhages. This unusual case illustrates discordance between apparent irreversible loss of cortical function as indicated by electrocerebral silence with preserved cerebral blood flow. The implications of these apparent paradoxical events will be discussed in the context of defining brain death in children.

Can prostate-specific antigen levels predict bone scan evidence of metastases in newly diagnosed prostate cancer?

Staging in prostate cancer, as in any other cancer has significant ramifications in management. Currently, prostate-specific antigen (PSA) determination and the bone scan are two important procedures in the pretreatment staging workup of prostate cancer. PSA is a very useful serum tumor marker in the management of prostate cancer patients. We retrospectively evaluated 90 patients at the time of initial diagnosis of prostate cancer, all of whom had initial PSA levels measured, as well as bone scans obtained. In addition to the PSA level, we considered clinical stage and pathologic grade in the prediction of bone scan for metastases, at the time of initial diagnosis of prostate cancer. Negative predictive value for PSA values < 10 ng/ml (27 patients), clinical stage A (9 patients) and pathologic grade 1 (19 patients) was 100%. The number of patients with bone scan evidence of metastasis with < 10 ng/ml and > 10 ng/ml PSA levels were 0% (0/27 patients) and 27% (17/63 patients) (p = .0022 [Fisher's Exact test]; p = .003 [chi-square test]). In patients with higher stage (p = .688), grade (p = .039), or PSA levels (p = .0001), the incidence of bone metastases increased. However, none of these three parameters can predict reliably bone scan evidence of metastases (i.e., positive predictive value). The negative predictive values did not improve when a combination of the two or three of the above parameters were used.

Improved detection of hepatic lesions using MoAb B72.3 and a modified 111In labelling technique in patients with recurrent colon cancer.

In this study, the clinical usefulness of 111In-SCN-Bz-diethylenetriaminepentaacetic acid (DTPA) monoclonal antibody (MoAb) B72.3 in patients with recurrent colorectal carcinoma was evaluated. In previous studies with radiolabelled MoAb B72.3, metastatic liver lesions in patients with colon cancer appeared as areas of either increased (hot lesions) or decreased (cold lesions) activity, and extrahepatic lesions appeared as areas of increased activity. Eleven patients were enrolled in this study, and 12 MoAb imaging study results were correlated with computed tomography/magnetic resonance imaging findings. The improved detection rates (number of hot lesions) in MoAb imaging were 48% (14/29) for hepatic metastases and 60% (6/10) for extrahepatic metastases. This represents a significant improvement in the rate of detection of metastatic disease of the liver in patients with recurrent colon cancer when compared to the rate in previous reports. Seventeen clinically unsuspected hepatic and extrahepatic areas of increased uptake were also identified on MoAb studies, and two of these areas were confirmed as metastatic disease at surgery. The rate of detection of extrahepatic metastases with 111In-SCN-Bz-DTPA MoAb B72.3 was also compared and found to be equal to the detection rates with other radiolabelled immunoconjugates. No major adverse side effects were noted during the administration of the MoAb. Four of nine patients tested had a positive anti-mouse antibody (HAMA) response 3 months after injection. These preliminary data indicate that this 111In-labelled immunoconjugate of MoAb B72.3 demonstrates an improvement in hepatic lesion detection rate than did previously reported preparations in patients with recurrent colon cancer.

Diffuse lung uptake of technetium-99m sulfur colloid associated with fatty liver disease of pregnancy.

Diffuse pulmonary uptake of sulfur colloid was seen in a 35-year-old postpartum white female with the presumptive diagnosis of fatty liver disease of pregnancy. As the disease process resolved, the pulmonary uptake of sulfur colloid disappeared. To the authors' knowledge, this scan association has not been previously reported.

The dual-isotope ProstaScint imaging procedure: clinical experience and staging results in 145 patients.

PURPOSE: Whole-body, regional planar, and SPECT imaging using the In-111-labeled monoclonal antibody capromab pendetide (In-111 MAb; ProstaScint) has been shown to increase the detection of early disease spread in patients with prostate cancer. However, recognition of metastatic tumor sites can be difficult, especially if the involved nodes are near blood vessels. We have developed an alternate approach to the identification of metastatic sites that is based on a single simultaneous In-111 MAb and Tc-99m RBC SPECT acquisition of the pelvis and abdomen on day 5 after injection. We have also developed software that dynamically subtracts the Tc-99m RBC data set (vascular component) from the In-111 MAb data set (prostate and lymph node component), which allows for easier identification of metastatic sites. METHODS: We evaluated the effectiveness of ProstaScint for staging 145 patients with prostate cancer, 19 newly diagnosed and 126 with recurrence, using these two modifications. RESULTS: With clinical follow-up in 13 of 19 (68%) patients with primary disease, 10 of 13 (78%) had organ-confined disease. With follow-up in 64 of 126 (51%) patients with possible recurrent disease, 49 of 64 (77%) were found to have prostatic fossa activity only. Disease stage was deemed more advanced in 3 of 13 (22%) patients with primary cancer and in 13 of 64 (20%) of those with recurrent disease based on ProstaScint findings when all other imaging tests were inconclusive. Six patients with recurrent disease had negative results of their scans. In the 16 patients with more advanced disease, 3 of 59 lesions (5%) were documented as false positive, and there were no reported cases of false-negative findings. CONCLUSIONS: Using both the dual-isotope procedure and the subtraction analysis software with the ProstaScint examination provides additional information for staging primary and possibly recurrent prostate cancer compared with standard imaging techniques.

Preoperative prediction of extent and severity of ischemic colitis by imaging with in-111 labeled leukocytes.

Ischemic colitis is a relatively common clinical entity. Conservative medical management is successful for most patients, but surgical intervention is required for patients with intractable disease. Noninvasive determination of the site and extent of the disease can be helpful in the preoperative decision on the surgical approach in these debilitated patients. However, current radiologic studies individually are inadequate in this respect. Based on the clinicopathologic correlation obtained after imaging with In-111 labeled leukocytes in a patient with ischemic colitis, the authors believe that this procedure may be useful; further studies in a larger patient population are warranted.

Ischemic colitis: Tc-99m HMPAO leukocyte scintigraphy and correlative imaging.

A 62-year-old woman became progressively ill after aorto-bifemoral graft surgery. A Tc-99m hexamethylpropyleneamine oxime (HMPAO) leukocyte scan was performed because of fever and suspected graft infection. The anterior abdominal and pelvic views demonstrated marked uptake within the sigmoid colon. Follow-up studies, including CT scan and contrast intestinal x-rays, confirmed the presence of an abnormal sigmoid loop. Subsequent surgical resection and pathological examination of the sigmoid colon revealed ischemic changes. To our knowledge, detection of ischemic colitis using Tc-99m HMPAO labeled leukocytes has not been reported. Clinical and routine radiological findings of ischemic colitis are typically nonspecific and may result in delayed diagnosis that can lead to high mortality. Tc-99m HMPAO leukocyte scintigraphy may be helpful in the noninvasive diagnosis of ischemic injury to the colon, especially after aortic graft surgery.

Detection of recurrent colon cancer with In-111 labeled MoAb B72.3 in a patient with normal CEA and TAG-72 levels.

The usefulness of radioimmunoscintigraphy with In-111 labeled MoAb B72.3 is illustrated in this case report of a patient with an aggressive cancer of the ascending colon. When used in conjunction with CT, ultrasound examination, and MRI, radioimmunoscintigraphy improved the specificity of these other imaging modalities, although the patient's serum CEA and TAG-72 levels remained within the normal ranges. In addition, MoAb imaging demonstrated superiority over CT in identifying an additional unsuspected lesion. Detection of occult disease by imaging modalities with or without elevated serum CEA levels is discussed.