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.

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.

Impact of radioimmunoscintigraphy on the management of colorectal and ovarian cancer patients: a retrospective study.

Noninvasive differentiation of benign from malignant disease has emerged as an important diagnostic challenge in the current age of health-care cost containment. Most physicians today acknowledge that early and accurate detection of cancer is important in successful treatment. Antibodies have been developed, labeled with radioactive isotopes, and used to detect and treat malignant tumors. During the past few years, several radiolabeled antibodies have received approval from the U.S. Food and Drug Administration for imaging colorectal, lung, ovarian, and prostate carcinomas, thus expanding and improving the physician's ability to detect and follow cancer in patients. At present, there is ample evidence in the literature to suggest that imaging with the 111In-labeled monoclonal antibody B72.3 is clinically useful for detecting primary/recurrent colorectal and recurrent ovarian carcinomas. In this article, we present a retrospective review of 136 patients from 10 moderate-sized hospitals who underwent a study with radioimmunoscintigraphy (RIS), using the 111In B72.3 antibody and standard diagnostic examinations for the detection of recurrent colorectal or ovarian carcinoma. The resulting data were analyzed in an effort to determine if (and how) information obtained from this radioimmunoscintigraphic procedure is being used by referring physicians. Our findings suggest a gradually increasing use of scan findings with the 111In B72.3 antibody in making patient-management decisions.

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.

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.

Cerebral perfusion SPECT imaging in epileptic and nonepileptic seizures.

Patients with epileptic and nonepileptic seizures are commonly encountered in clinical practice, and they can pose a difficult diagnostic problem. We present two cases that show the difficult task of differentiating between true epileptic and nonepileptic or psychogenic seizures in some patients. The clinical presentations were complex and the use of video-monitored EEG alone was insufficient to make definitive diagnoses. Ictal and interictal Tc-99m HMPAO brain perfusion SPECT imaging examinations were used to help establish the correct diagnoses. This report describes the advantage of using the brain perfusion SPECT imaging examination. The injection of stabilized Tc-99m HMPAO during an ictal event followed by appropriate medical therapy provides a method of obtaining a reasonable image of relative perfusion (activity) during the seizure. These images can then be compared with interictal examinations and an epileptic or nonepileptic focus may be localized. The Tc-99m HMPAO brain perfusion SPECT imaging study was helpful in establishing the correct diagnosis in both cases.

Application of ictal brain SPECT for differentiating epileptic from nonepileptic seizures.

The authors report 2 clinical cases that illustrate the difficulties with video-monitored EEG and the advantages of brain SPECT in differential diagnosis of true epileptic seizures and nonepileptic seizures. Injection of [99mTc]HMPAO at the time of the ictal event provides a means to obtain a SPECT image postictally for comparison with interictal examinations so that an epileptic or nonepileptic focus may be localized.

Epilepsia inducida por música / Musicogenic epilepsy induction

Musicogenic epilepsy is a rare entity. It used to be considered a form of auditory evoked epilepsy. However, the theme of the music as the trigger of a partical complex seizure and likely, the memory components while listening to the music, suggest that this seizure disorder, might well be a disorder of a higher cognitive function. Therefore, it could be included within the affective epilepsy group. The case report we present in this paper, confirms the diagnosis of musicogenic epilepsy and the role of brain spect in reaching that diagnosis

New methods for the staging of colorectal cancer using noninvasive techniques.

Noninvasive differentiation of benign from malignant disease has emerged as an important diagnostic challenge in this age of health-care cost containment. Most physicians today acknowledge that early and accurate detection of cancer is the key to successful treatment. Antibodies have been developed and used to detect and treat tumors. In the next few years, several radiolabeled antibodies will likely receive FDA approval for imaging colorectal, lung, and prostate carcinomas, thus expanding and improving the physician's ability to detect and follow cancer in patients. There is ample evidence in the literature that suggests that imaging with labeled antibodies is clinically useful for detecting colorectal cancer in patients with suspected recurrence, in patients with presumed isolated resectable liver metastasis, and in those at high risk of the development of recurrence. This paper reviews these studies, and also discusses some data obtained from positron emission tomography (PET) imaging in colorectal patients.

Tc-99m sestamibi uptake in infiltrating ductal carcinoma of the breast in a male patient.

A 73-year-old man had an asymptomatic, slowly growing breast nodule. The mammographic appearance was highly suspicious of a malignancy, but the patient refused to undergo a biopsy. Because breast carcinoma has been previously described to accumulate Tc-99m MIBI in women, mammoscintigraphy was performed as a complementary examination. Uptake of the agent was noted.

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.

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).

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.

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).

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.

Recent advances in the detection of ovarian cancer: a review.

Epithelial ovarian cancer is one of the more aggressive malignancies among American women today, and its incidence is increasing. The major obstacle in combatting ovarian cancer is the remarkable lack of symptoms in early-stage disease. Symptoms usually occur in advanced stages when tumor dissemination within the peritoneal cavity induces ascites with resultant increasing abdominal girth. Physicians have been unable to reach women who have early-stage ovarian cancer, a time when a high cure rate could be expected. However, during the past few years, significant developments in the areas of serum tumor markers, transvaginal ultrasonography with color flow Doppler analysis, immunodiagnostic techniques, and immunotherapy have been reported. These new modalities show promise for use in the early diagnosis and treatment of ovarian cancer. The authors review some of the new data and discuss patient outcomes when these new modalities are 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.