Michael J. Blend

VIP grafted sterically stabilized liposomes for targeted imaging of breast cancer: in vivo studies.

Targeted delivery of radionuclides and therapeutic agents to specific biomarkers of breast cancer has important implications for the diagnosis and therapy of breast cancer. Vasoactive intestinal peptide receptors (VIP-R) are approximately five times more expressed in human breast cancer, compared to normal breast tissue. We have used VIP, a 28 amino acid mammalian neuropeptide, as a breast cancer targeting moiety for targeted imaging of breast cancer. VIP was covalently attached to the surface of sterically stabilized liposomes (SSL) that encapsulated a radionuclide, Tc99m-HMPAO. Rats with n-methyl nitrosourea (MNU)-induced in situ breast cancers were used to test this targeted liposomal imaging agent. Specifically, the pharmacokinetics and biodistribution of Tc99m-HMPAO encapsulating SSL with and without VIP were determined together with their ability to image breast cancer. The presence of VIP did not alter the size and Tc99m-HMPAO encapsulation ability of SSL. It also did not alter the pharmacokinetic profile of SSL. Long-circulating liposomes with and without VIP on their surface accumulated at significantly higher quantities in breast cancer when compared to normal breast, indicating passive targeting of these constructs to cancer tissues. Importantly, in breast cancer, Tc99m-HMPAO encapsulating SSL with VIP showed significantly more accumulation than SSL without VIP. The tumor to non-tumor ratio was also significantly higher for Tc99m-HMPAO encapsulating VIP-SSL than Tc99m-HMPAO encapsulating SSL without VIP, suggesting active targeting of VIP-SSL to breast cancer. Collectively, these data showed that Tc99m-HMPAO encapsulating VIP-SSL can be successfully used for the targeted imaging of breast cancer.

Recurrence of Thyroid Nodules after Surgical Removal in Patients Irradiated in Childhood for Benign Conditions

To determine the incidence of benign thyroid nodules and the risk factors for their recurrence after surgical removal, we followed 511 patients for 1 to 40.6 years (median, 11.2) after surgery for benign thyroid nodules arising after local irradiation for unrelated benign diseases in childhood. Recurrent thyroid nodules developed in 100 patients (19.5 percent). The risk of recurrence correlated inversely with the amount of thyroid tissue removed. Women had a higher recurrence rate than men (28.4 percent vs. 10.3 percent; P less than 0.05). Among the 299 patients who had been treated with thyroid hormone at the discretion of their physicians to suppress thyroid-stimulating hormone, 25 had recurrences (8.4 percent), as compared with 72 of 201 patients who did not receive thyroid hormone (35.8 percent) (hazard ratio taking into account the extent of surgery and the patients sex, 2.5; 95 percent confidence interval, 1.5 to 4.1). Histologic analysis of the 73 tissue samples from patients with recurrences showed that 14 samples (19.2 percent) were malignant. Thyroid hormone treatment had no effect on the rate of thyroid cancer. We conclude that radiation-associated benign thyroid nodules have a high recurrence rate, similar to that reported among nonirradiated patients with benign thyroid nodules. We also conclude that treatment with thyroid hormone decreases the risk of benign recurrences, particularly in women, but not the risk of cancer.

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.

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.

Impact of cognitive rehabilitation therapy on neuropsychological impairments as measured by brain perfusion SPECT: a longitudinal study

Three patients, with known brain injury and neuropsychological impairments, are followed through an individualized cognitive rehabilitation programme and post discharge from the treatment programme. Single Photon Emission Computed Tomography (SPECT) of the brain was employed to evaluate resting relative cerebral blood flow (rCBF) during the process of recovery from brain injury. All patients experienced significant improvements on measures of neuropsychological functioning and improvements in rCBF during this longitudinal study. The specific changes in rCBF appear to be related to the location of the patients brain injury and strategies particular to cognitive rehabilitation therapy. Continued improvements in rCBF, functional abilities, and cognitive skills were documented in these three cases up to 45 months post brain injury.

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 [Fishers 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.

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 physicians 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.

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.

Splenic uptake of Tc-99m MDP in a patient with hemochromatosis.

A 43-year-old man with a history of a liver transplantation for hepatocellular carcinoma and hemochromatosis was admitted because of syncope. His serum ferritin level was elevated. A bone scan revealed posttraumatic changes in the ribs and diffuse uptake in the spleen. This splenic activity, which has been reported in other iron deposition diseases, was thought to be related to the patients hemochromatosis. Obviously, previous radionuclide imaging must be excluded when splenic uptake is seen on a bone scan.

Localization of human sarcoma with radiolabeled monoclonal antibody

SummaryThe early localization of recurrent or metastatic sarcoma remains a challenging clinical problem. 125I-labeled monoclonal antibody (Mab) 19–24, produced in our laboratories against a human malignant fibrous histiocytoma, has been evaluated for detection of locally recurrent or metastatic disease in selected sarcoma patients. In vitro testing indicated various degrees of positive Mab reactivity with most sarcoma types, and low but significant reactivity with some nonsarcoma tumors and several normal tissues, including liver. The iodine-labeled Mab had an immunoreactivity of 90% and a high binding constant (8.1×109M−1). Biodistribution studies of radioisotope in sarcoma patients showed rapid clearance of radiolabeled from the blood and uptake in tumor deposits, liver, and spleen. A differential in radioactivity kinetics between liver and tumor was also found. Serial patient scanning determined optimal imaging time to be between 24 and 48 h after i.v. infusion of the radiolabeled Mab. Analysis of tissues obtained during surgery (including a dual antibody-label study using a nonspecific Mab) showed selective localization of the Mab into the sarcoma deposits. Radiolabeled Mab shows potential as a clinically useful tool for localization of sarcoma deposits.