Bruce A. Porter

Radiolabeled-Antibody Therapy of B-Cell Lymphoma with Autologous Bone Marrow Support

BACKGROUND Radiolabeled monoclonal antibodies recognizing B-lymphocyte surface antigens represent a potentially effective new therapy for lymphomas. We assessed the biodistribution, toxicity, and efficacy of anti-CD20 (B1 and 1F5) and anti-CD37 (MB-1) antibodies labeled with iodine-131 in 43 patients with B-cell lymphoma in relapse. METHODS Sequential biodistribution studies were performed with escalating doses of antibody (0.5, 2.5, and 10 mg per kilogram of body weight) trace-labeled with 5 to 10 mCi of 131I. The doses of radiation absorbed by tumors and normal organs were estimated by serial gamma-camera imaging and tumor biopsies. Patients whose tumors were estimated to receive greater doses of radiation than the liver, lungs, or kidneys (i.e., patients with a favorable biodistribution) were eligible for therapeutic infusion of 131I-labeled antibodies according to a phase 1 dose-escalation protocol. RESULTS Twenty-four patients had a favorable biodistribution, and 19 received therapeutic infusions of 234 to 777 mCi of 131I-labeled antibodies (58 to 1168 mg) followed by autologous marrow reinfusion, resulting in complete remission in 16, a partial response in 2, and a minor response (25 to 50 percent regression of tumor) in 1. Nine patients have remained in continuous complete remission for 3 to 53 months. Toxic effects included myelosuppression, nausea, infections, and two episodes of cardiopulmonary toxicity, and were moderate in patients treated with doses of 131I-labeled antibodies that delivered less than 27.25 Gy to normal organs. CONCLUSIONS High-dose radioimmunotherapy with 131I-labeled antibodies is associated with a high response rate in patients with B-cell lymphoma in whom antibody biodistribution is favorable.

Magnetic resonance imaging of the bone marrow in patients with leukemia, aplastic anemia, and lymphoma

Magnetic resonance imaging (MRI) of the bone marrow was performed in 29 patients with leukemia, aplastic anemia, or lymphoma who were scheduled for bone marrow transplantation, and in 12 normals. T1-weighted coronal images (TR600/TE40) of the pelvis and proximal femurs demonstrated marrow pathology in adult patients. A simple MR grading system was developed to classify patterns of marrow involvement, and MR grading of cellularity was correlated with marrow histology. Normal marrow produced a relatively high signal intensity reflecting the predominance of short T1 fat in the marrow space. MRI of pretransplant patients with chronic myelogenous leukemia and acute leukemia in relapse demonstrated a markedly decreased marrow signal, consistent with the replacement of marrow fat by longer T1 neoplastic tissues. Aplastic anemia could not be differentiated from normal with the pulse sequences employed. Marrow involvement by Hodgkins lymphoma was detected as diffuse marrow infiltration with superimposed focal areas of even lower signal intensity, reflecting the nodular nature of Hodgkins. These results indicate that infiltrative marrow disorders can be sensitively detected by MRI.

Early diagnosis of spinal metastases by CT and MR studies.

Fifteen patients with known metastatic or high-risk primary cancer, normal neurologic examinations, and new abnormalities on 99mTc bone scan were evaluated with spinal CT and magnetic resonance (MR) imaging. Four patients underwent CT metrizamide myelography. Spinal CT and MR agreed in 14 of 15 patients demonstrating spinal metastases in 12 patients and benign disease in two. In one patient spinal CT was normal, but MR showed altered marrow signal consistent with metastatic disease. Epidural tumor was demonstrated by CT metrizamide myelography in four cases, all correctly identified by MR. Further evaluation of spinal MR in this setting is warranted.

MR imaging of hemorrhagic adnexal masses.

Magnetic resonance (MR) imaging, performed on 31 women with 40 surgically proven adnexal masses, was reviewed to determine whether MR can distinguish hemorrhagic from nonhemorrhagic masses. Fourteen masses proved to be hemorrhagic at surgery including functional ovarian cysts (seven cases), cystadenoma (one case), endometriomas (three cases), hematosalpinx (one case), ectopic pregnancy (one case), and parametrial extension from cervical carcinoma (one case). A high signal intensity (compared with adjacent pelvic fat) on a Tl-weighted spin echo sequence was found to be a reliable indicator of hemorrhage and was demonstrated in all 14 hemorrhagic masses. The “hematocrit” effect was seen as an area of high signal intensity layering in the dependent portion of six hemorrhagic cysts. Only four of 26 nonhemorrhagic masses demonstrated high signal intensity on Tl-weighted sequences and, of these, three proved to be fat-containing dermoid cysts and one was a simple cyst with adherent mesenteric fat. We conclude that high signal intensity on a Tl-weighted spin echo pulse sequence is evidence for a hemorrhagic mass and that a hematocrit effect appears to be a specific sign for a hemorrhagic cyst. The clinical significance of hemorrhagic adnexal masses is discussed.

(18)F-FDG PET/CT-positive internal mammary lymph nodes: pathologic correlation by ultrasound-guided fine-needle aspiration and assessment of associated risk factors.

OBJECTIVE Metastatic breast cancer in internal mammary (IM) lymph nodes is associated with a poor prognosis. This study correlates (18)F-FDG PET/CT-positive IM lymph nodes with ultrasound-guided fine-needle aspiration (FNA) cytopathologic results and determines risk factors for IM node positivity on PET/CT. MATERIALS AND METHODS For this retrospective study, a database search was performed to identify patients referred for whole-body (18)F-FDG PET/CT for initial staging or restaging of breast cancer from January 1, 2005, through December 31, 2010. The radiology reports and images were reviewed for patients with (18)F-FDG-avid IM lymph nodes on PET/ CT and correlated with the cytopathologic results from FNA of selected PET/CT-positive IM lymph nodes. The patients with positive IM nodes on PET/CT who underwent PET/CT for initial staging were compared against age-matched and tumor size-matched patients to identify risk factors for IM node positivity on PET/CT. RESULTS One hundred ten of 1259 patients (9%) had an (18)F-FDG-avid IM lymph node on PET/CT. Twenty-five patients underwent ultrasound-guided FNA of a suspicious IM node, and 20 IM lymph nodes (80%) were cytologically proven metastases from the primary breast malignancy. High tumor grade, the presence of lymphovascular invasion (LVI), and triple receptor-negative hormonal receptor status were found to be significant risk factors for IM node positivity on PET/CT (p < 0.05). CONCLUSION Although fewer than 10% of breast cancer patients have positive IM nodes on (18)F-FDG PET/CT performed for initial staging or restaging, a positive IM node indicates a very high likelihood of malignant involvement on ultrasound-guided FNA. The presences of high tumor grade, LVI, or triple receptor-negative status are risk factors for IM node positivity on (18)F-FDG PET/CT.

Magnetic resonance imaging of soft tissue masses.

Twenty-nine soft tissue masses were studied with magnetic resonance imaging (MRI) which proved to be useful in the preoperative evaluation of these lesions. Other imaging modalities employed had significant limitations. Plain films were of little value because of the intrinsically low contrast of soft tissues. Angiography was not necessary unless MRI suggested a vascular lesion or proximity to major blood vessels. Computed tomography (CT) and MRI both readily identified fatty lesions and their relationship to adjacent structures. Some soft tissue tumors could not be delineated from normal muscle with CT, but were easily seen with MRI. MRI is ideally suited for the study of suspected soft tissue tumors because of its excellent soft tissue contrast and its ability to image directly in any plane. Optimum evaluation required imaging in at least two planes with spin echo sequences chosen to bring out both T1 and T2 features.

Contrast-Enhanced Magnetic Resonance Mammography

Rationale and Objectives. We refined and evaluated a spin-echo-based dynamic MR mammography technique for detection and characterization of benign and malignant breast masses. Methods. Analysis was performed on 75 magnetic resonance (MR) mammographies done at 0.5-T on 67 consecutive patients. Histological confirmation of malignancy and MR enhancement data were available on 33 cancers; 29 were infiltrating ductal carcinomas. Precontrast short inversion time (TI) inversion recovery images (TR 2000, TE 30, TI 110) were obtained as well as serial dynamic pre- and postcontrast T1-weighted spin-echo images (TR 600, TE 12) after bolus injection of 0.1 mmol/kg gadolinium chelate. An image subtraction technique was used, and tissue enhancement (expressed as a percentage of baseline signal intensity) was calculated for immediate (0 min) and delayed (8 min) studies. Lesion enhancement was compared to normal parenchyma, fat, muscle, and cysts. Coronal and sagittal reformatted images were also produced. Three cancers were studied during chemotherapy. Results. The mean immediate and delayed tumor enhancement values were 81 ± 22% and 84 ± 23%, respectively. Other tissue values were (immediate, delayed): normal breast, 7% and 19%; fat, 4% and 4%; muscle, 11% and 12%; cysts, 0% and 0%. Fibroadenomas may enhance as quickly and intensely as tumors, but are smooth and usually septated. Image subtraction substantially increased lesion contrast, although motion artifact and misregistration can compromise image quality and quantitation. Conclusion. Breast cancers enhance 10 times or more than normal breast parenchyma; this, together with the image subtraction method, results in high lesion conspicuity. Both quantitative enhancement profiles and morphological criteria are necessary to differentiate benign from malignant lesions. Although the technique, interpretive criteria, and indications are still evolving, MR mammography may play an important role in the future detection and staging of breast cancer.

Emerging technologies in surgical planning for breast cancer

BACKGROUND Computer-assisted diagnosis (CAD) has been applied to mammography and chest radiography to improve diagnostic accuracy, and has the potential to improve the accuracy of magnetic resonance imaging (MRI) for detecting nodal metastases in women with newly diagnosed breast cancer. METHODS Six women with newly diagnosed breast cancer underwent MRI of the breast and axilla. Radiologists applied digital tissue recognition (DTR), a form of CAD, to the MR images to detect nodal metastases. The results were compared with clinical staging and to surgical pathology. RESULTS The accuracy of clinical staging for the 6 subjects was 3 of 6 (50%), and with DTR-MRI it rose to 6 of 6 (100%). CONCLUSIONS DTR-MRI is a potential method for noninvasively detecting axillary nodal involvement in women with newly diagnosed breast carcinoma.