Eugene A. Cornelius

Mechanism of technetium 99m sestamibi parathyroid imaging and the possible role of p-glycoprotein

BACKGROUND Localization of parathyroid glands is critical in the treatment of recurrent or persistent hyperparathyroidism. Technetium sestamibi imaging may improve localization; however, the mechanism of visualization of parathyroid tissue remains unclear. On the basis of the chemical structure of sestamibi it has been suggested that p-glycoprotein is involved in the transport of sestamibi across cell membranes. This study was designed to examine sestamibi uptake and retention and p-glycoprotein expression in normal and abnormal parathyroid tissue. METHODS Thirty-two consecutive patients underwent 2-methoxy-isobutyl-isonitrile imaging immediately before parathyroid exploration. Tissue was obtained from normal and abnormal parathyroids and from the thyroid gland. Touch preparations gave rapid confirmation of tissue origin. Specimens were trimmed and weighed, and gamma-emission was counted. Percentage injected dose per gram of tissue was calculated. Immunohistochemistry was obtained with a battery of monoclonal antibodies to identify p-glycoprotein in parathyroid tissue submitted for permanent histologic examination. Slides were graded by a pathologist familiar with immunohistochemistry. RESULTS Abnormal parathyroid tissue had a higher mean retention of injected dose per gram than did normal thyroid and parathyroid tissue. Immunohistochemistry revealed that abnormal parathyroid tissue expresses less p-glycoprotein. CONCLUSIONS These results suggest that size is not the single determinant of parathyroid visualization and that p-glycoprotein expression may be involved in the mechanism of parathyroid imaging.

Rapid immunological induction of murine lymphomas: evidence for a viral etiology.

A graft-versus-host reaction induced in (SJL/J x C57BL/1)F1 hybrid mice by injection of SJL/J spleen cells resulted in 100 percent incidence of tumors at 40 days. Transplantation studies revealed that the tumors were antigenically C57BL/1. Since both SJL/J and C57BL/1 mice carry tumorigenic virus, the evidence suggests a viral etiology.

Nuclear medicine imaging in rhabdomyolysis

A case of severe rhabdomyolysis is reported in which, some seven and one-half weeks after its occurrence, a gallium scan was strongly positive, due to abscess formation in the damaged muscle. A bone scan was weakly positive in the same area, due to gallium photons. A review of the few reported cases reveals that bone scans are a very sensitive indicator of acute muscle damage and are useful to monitor its repair.

Problems in the imaging diagnosis of hepatoma

Two problem cases in the imaging diagnosis of hepatoma are reported. In both, a defect on the standard liver scan showed preferential gallium uptake. Ultrasound findings for a mass lesion were inconsistently present or absent. However, in the given clinical setting, a diagnosis of hepatoma was made. The microscopic changes suggested that the poor ultrasound demonstration of the tumors was due to marked fibrosis of the liver both outside and inside the tumor.

False tumor-positive lymph nodes in radioimmunodiagnosis and radioimmunoguided surgery: etiologic mechanisms.

We investigated the causes of false‐positive (nontumor cell) focal uptake in radioimmunodiagnosis (RAID) and false‐positive high counts in radioimmunoguided surgery (RIGS). Tissue blocks of two such RAID cases were recut and examined by immunohistochemistry (IH) (group 1). Lymph nodes in the drainage area of 14 colon cancers selected because of tumor‐positive draining nodes were examined similarly (group 2). The lymph nodes in group 1 showed nontumor cell germinal center (GC) and rare macrophage (Mϕ positivity with monoclonal antibody (mAb) CC49 to tumor antigen (Ag) TAG‐72, the same Ag to which the mAb B72.3, used for the RAID studies, was directed. In group 2, CC49 staining was observed in the colon cancers, in noncellular tumor Ag in lymphatic channels, and in the GC of draining nodes in a pattern similar to that of follicular dendritic cells (FDC). An In‐111‐mAb/tumor Ag (TAG‐72 or CEA) complex can result in false‐positive RAID/RIGS studies by In‐111 retained in the lysosomes of lymph node Mϕ, following attachment of the mAb to the Ag, and their catabolism in the Mϕ. An 1‐125‐mAb to either tumor Ag could lead to false‐positive RIGS studies due to its attachment to the Ag portion of ag/ab complexes affixed to the FDC in the GC of the lymph nodes draining a tumor.

Sensitivity and Efficacy Indices for Oncologic Data Reporting

As bioactive tracers such as radioactive antibodies and other tumor imaging agents are put to wider clinical use, it becomes increasingly difficult to reconcile data from various centers since they report tumor imaging results in a variety of different ways. The most commonly encountered problem is caused by differences in the method of data reporting. One center will describe sensitivity of detection by site of lesion, while another will report sensitivity of detection on a per-patient basis. An example of the confusion caused by differences in methods of data recording can be found in a recent review by DeLand and Goldenberg of their work with anti-CEA antibody studies in a series of 173 patients (1). These cases included 36 patients with lung and breast carcinoma. In this subgroup, 20 of 30 primary lesions and 12 of 17 metastases were visualized. These data are surprising since our own experience with metastatic lung and breast carcinoma suggests that these patients commonly have multiple metastatic lesions (e.g., widespread bony metastases). As a result, we wonder why the number of “known” metastases is not significantly greater than the 17 lesions present in the DeLand and Goldenberg series. As a consequence, these data raise questions about patient selection, or standards and meaning of tumor verification in the reporting of oncologic results.

Immunology, virology, and cancer

N THE LAST 10 yr, intensive research in the exciting areas of oncogenic viruses and tumor immunology has revealed a great deal about the causes of cancers in animals, and how they grow. Many such tumors are caused by viruses. In this review, this research and the research on putative human tumor viruses will be summarized. The already substantial evidence that immune processes are involved in surveillance against cancer will be reviewed. The apparently paradoxical situation of tumor escape from this surveillance will be explained. Finally, the present and future possibilities in immunotherapy, immunodiagnosis, and immunoprophylaxis of cancer will be briefly outlined. From the point of view of general clinical application, present knowledge is still embryonic. Zealous investigation at all levels, from embryology and molecular biology to epidemiologic studies and clinical trials is justifiable, for the potential benefits to mankind are incalculable.