Lawrence C. Swayne

Phase I/II trial of 131I‐MN‐14 F(ab)2 anti–carcinoembryonic antigen monoclonal antibody in the treatment of patients with metastatic medullary thyroid carcinoma

Monoclonal antibodies (MAbs) against carcinoembryonic antigen (CEA) have been recognized as targeting agents for medullary thyroid carcinoma (MTC). This Phase I/II study was initiated to determine the safety, maximum tolerated dose (MTD), and therapeutic potential of 131I‐MN‐14 F(ab)2 anti‐CEA MAb for patients with metastatic MTC.

CT and MR imaging in cystic abdominal lymphangiomatosis.

We report the ultrasound, CT, magnetic resonance, and pathologic findings in a patient with cystic lymphangiomatosis of the retroperitoneum, liver, spleen, pancreas, left kidney, somatic soft tissues, and bone. Unusual features of this case include multiple organ involvement and the patients relatively benign clinical course.

Improved detection of medullary thyroid cancer with radiolabeled antibodies to carcinoembryonic antigen.

PURPOSE This investigation was undertaken to assess the targeting of established and occult medullary thyroid cancer (MTC) with radiolabeled monoclonal antibodies (MAbs) reactive with carcinoembryonic antigen (CEA). PATIENTS AND METHODS Twenty-six assessable patients with known (n = 17) or occult (n = 9) MTC were studied with radiolabeled anti-CEA MAbs. Scintigraphic images were collected to determine targeting of tumor lesions. RESULTS The targeting results of technetium 99m (99mTc)-,iodine 123 (123I)-, and iodine 131 (131I)-labeled anti-CEA antibodies (all directed against the same epitope of CEA) indicated that all these reagents were capable of detecting established and occult MTC. The sensitivity for detection of known sites of disease ranged from 76% to 100% for the various anti-CEA MAbs used, when compared with computed tomography (CT), magnetic resonance imaging (MRI), bone scan, or other imaging modalities. Moreover, the antibody scan was positive in seven of nine patients with occult disease (patients with negative conventional imaging studies, but who had elevated calcitonin and/or CEA levels). Three of seven patients underwent surgery and the disease was confirmed by histopathology in all three. CONCLUSION Anti-CEA MAbs are excellent agents for imaging recurrent, residual, or metastatic MTC. The high lesion sensitivity in patients with known lesions, combined with the ability to detect disease, may make these agents ideal for staging patients, monitoring disease pretherapy or posttherapy, and especially for evaluating patients with recurrent or persistent hypercalcitonemia or CEA elevations after primary surgery. Analogous to radioiodine in the evaluation of patients with differentiated thyroid cancer, radiolabeled anti-CEA MAbs may achieve a similar role in diagnosing and monitoring patients with MTC.

Lymphoma imaging with a new technetium-99m labelled antibody, LL2

The lesion detection capability of a new technetium-99m labelled B-cell lymphoma monoclonal antibody (MoAb) imaging agent, LL2, was evaluated in 8 patients with non-Hodgkins lymphoma and 1 patient with chronic lymphocytic leukaemia. The MoAb kit consists of a 1-vial, 1-mg Fab′ form of LL2 ready for instant labelling with technetium. The patients were injected with ∼ 925 MBq (25 mCi) of 99mTc-LL2 Fab′ (1 mg), and planar and single photon emission tomography (SPET) studies were performed at 3–4 h post injection and at 24 h. There was no evidence of thyroid or stomach activity up to 24 h. Uniform splenic uptake was seen in all patients. Two non-lymphoma patients were also administered with the same agent and demonstrated a similar splenic distribution; therefore, splenic targeting was not scored as tumour-specific. A total of 29 from 48 tumour sites were detected by scintigraphy, including tumours of various grades and histological types. Excluding 1 patient who had a large tumour burden of over 500 g, 29 of 33 lesions were detected. One patient was free of disease at the time of the study and had a negative scan. Another patient showed excellent targeting of gallium-negative sites in the liver and bone. The bone involvement was not known prior to the antibody study and was subsequently confirmed by a bone scan. Additional sites of MoAb localization could not be followed in this group, since most patients went on to radioimmunotherapy immediately following the 99mTc-LL2 study. However, these initial results suggest that this new 99mTc-labelled antibody imaging kit should be further investigated for its potential role in the staging and follow-up of lymphoma patients.

Clinical evaluation of tumor targeting with the anticarcinoembryonic antigen murine monoclonal antibody fragment, MN-14 F(ab)2

The initial clinical experience with the second‐generation, high‐affinity, MN‐14 immunoglobulin (IgG) anticarcinoembryonic antigen (CEA) monoclonal antibody (MoAb) in patients with CEA‐producing tumors was reported previously. A bivalent fragment of this MoAb, MN‐14 F(ab)2, was prepared, and its pharmacokinetics, targeting properties, dosimetry, and immunogenicity were investigated.

Phase I clinical evaluation of a new murine monoclonal antibody (mu-9) against colon-specific antigen-p for targeting gastrointestinal carcinomas

Background. Colon‐specific antigen‐p is a tumor‐associated antigen present in approximately 60% of colorectal cancers. Preclinical studies have shown that the murine monoclonal antibody Mu‐9 has excellent tumor‐targeting abilities; therefore, clinical studies were initiated.

Improved selection of patients for reoperation for medullary thyroid cancer by imaging with radiolabeled anticarcinoembryonic antigen antibodies

BACKGROUND This study examined the utility of using radiolabeled anticarcinoembryonic antigen (CEA) monoclonal antibodies (MAbs) as a noninvasive imaging method to aid in the selection of patients for reoperation after operation for medullary thyroid carcinoma (MTC). METHODS Sixteen patients with persistent or recurrent hypercalcitoninemia since operation or MTC, but had negative or equivocal conventional imaging study results, were given 99mTc-, 123I-, or 131I-labeled NP-4 or MN-14 anti-CEA MAbs. Scintigraphic images were then performed to determine detection of tumor lesions. RESULTS The MAb scans were positive in 13 (81%) of the 16 patients studied. However, in only three of 13 patients was disease confined to the cervical or mediastinal nodes. In 10 patients, disease was additionally or solely found in distant organs such as liver (five patients), bone (four patients), and periaortic nodes (one patient). On the basis of our studies, only three of the 13 patients with positive scans would benefit from repeat neck exploration, another three would possibly benefit from neck or mediastinal exploration and hepatic resection, and the remaining seven patients would not benefit from any reoperation with curative intent. CONCLUSIONS MTC imaging with anti-CEA MAbs could be very useful in determining the ideal candidates for repeat neck exploration.

Three-phase bone imaging in bone marrow edema of the knee.

Transient bone marrow edema has been thought to be related to other similar entities including transient regional osteoporosis and spontaneous osteonecrosis. Although the findings of three-phase bone imaging have been described in osteonecrosis, scant attention has been paid in the nuclear medicine literature to patients with transient bone marrow edema. The authors report the findings of three-phase bone imaging in two patients with knee pain and a transient bone marrow edema pattern as documented by MRI.

False-positive hepatic blood pool scintigraphy in metastatic colon carcinoma.

A rare false-positive red blood cell scintigram occurred in a 49-year-old woman with two metastases from a primary adenocarcinoma of the sigmoid colon. Although the blood flow and static planar images were unremarkable, a 1-hour postinjection SPECT study showed a focus of increased activity in the inferior right lobe and a second photopenic focus in the dome. Following a trisegmentec-tomy, pathologic examination revealed the two metastases with no evidence of a hepatic hemangioma. Microscopy, however, showed a discrete area of nonspecific reactive changes (focal sinusoidal dilation and congestion) immediately adjacent to the metastasis in the inferior right lobe. It is postulated that the SPECT focus of increased activity occurred secondary to the labeled blood pool within the area of sinusoidal dilation, rather than within the adjacent metastasis.

MR findings in congenital glenoid dysplasia.

The MR features of congenital glenoid dysplasia are described. Osseous changes include both dysplasia of the glenoid and hypoplasia of the glenoid process. In addition, there are cartilaginous changes with hypertrophy of both the articular cartilage and the glenoid labra.