John O. Olsen

Immunoscintigraphy with indium-111-capromab pendetide: evaluation before definitive therapy in patients with prostate cancer.

OBJECTIVES No standard noninvasive diagnostic test reliably differentiates patients with organ-confined prostate cancer from those with lymph node metastases. The ability of a radiolabeled monoclonal antibody, indium-111 (111ln)-capromab pendetide, to identify sites of metastatic disease in patients at moderate to high risk of nodal involvement was investigated. METHODS The study prospectively evaluated 160 patients with prostate cancer scheduled to undergo pelvic lymph node dissection (PLND) before or during definitive treatment. All were at relatively high risk of nodal involvement by virtue of significantly elevated baseline prostate-specific antigen (PSA) values, Gleason scores, and/or locally advanced clinical stages of disease. The histologic findings of the PLNDs were compared with the results of immunoscintigraphy, computed tomography, and magnetic resonance imaging. RESULTS Among the 152 evaluable patientS studied with 111In-capromab pendetide before PLND, the sensitivity of immunoscintigraphy for lymph node detection was 62% and the specificity was 72%; the positive predictive value was 62% and the negative predictive value was 72%. In comparison, the sensitivity of computed tomography and magnetic resonance imaging was 4% and 15%, respectively, and the specificity was 100% for both procedures on the basis of a large number of negative interpretations. Logistic regression analysis revealed that immunoscintigraphy with 111In-capromab pendetide provided strong, independent evidence of the presence of lymph node metastases. Furthermore, the analysis indicated that certain combinations of PSA, Gleason score, and 111In-capromab pendetide were particularly effective at predicting the risk of nodal involvement. CONCLUSIONS Immunoscintigraphy with 111In-capromab pendetide outperformed standard diagnostic imaging techniques in the detection of prostate cancer lymph node metastases and provided independent prognostic information that complemented PSA, Gleason score, and clinical stage.

Somatostatin receptor imaging of neuroendocrine tumors with indium-111 pentetreotide (Octreoscan)

Somatostatin, a naturally occurring 14-amino acid peptide, can be thought of as an anti-growth hormone and functional down-regulator of sensitive tissue. Most neuroendocrine tumors seem to possess somatostatin receptors in sufficient abundance to allow successful scintigraphic imaging with radiolabeled somatostatin congeners. Several of these, including Indium-III-DTPA Pentetreotide (Octreoscan [Mallinckrodt Medical, St. Louis, MO]), which was approved for clinical use by the Food and Drug Administration in June 1994, have been of considerable value in scintigraphically identifying various neuroendocrine tumors. The Octreoscan compares favorably with other imaging modalities. The success of somatostatin receptor imaging in evaluating patients with suspected neuroendocrine tumors, including identifying otherwise radiographically occult lesions, has resulted in ranking somatostatin receptor imaging as the prime imaging procedure in patients with suspected neuroendocrine tumors at The Ohio State University.

Intraoperative radioimmunodetection of colorectal tumor with a hand-held radiation detector

A hand-held gamma detection probe was used intraoperatively to localize primary and recurrent colorectal tumors in 28 patients 48 to 72 hours after they received an intravenous injection of 2.2 mCi of iodine-131 labeled anticarcinoembryonic antigen polyclonal baboon antibody. Preoperative evaluation included determination of serum carcinoembryonic antigen, barium enema, colonoscopy, chest film, computerized axial tomography, liver, spleen, and bone scans, and endoscopy when indicated. Preoperative whole-body imaging correctly localized primary tumors in only 33 percent of the patients, whereas it correctly demonstrated tumor in 64 percent of those with recurrent disease. Intraoperative tumor-to-background ratios derived from the detector probe were elevated in all patients, averaging 3.97:1 in primary lesions and 4.18:1 in recurrent tumors. Postoperatively, carcinoembryonic antigen was localized in tissues with the avidin-biotin peroxidase staining technique to confirm intraoperative readings. Variations in stain uptake in a patient could be correlated with variations in radiation detector readings in the same patient. Results support our previous work in nude mice, demonstrating the improved sensitivity and specificity of the hand-held gamma detection device over whole-body imaging for intraoperative localization of immunoradiolabeled tumors.

A gamma-detecting probe for radioimmune detection of CEA-producing tumors

The detection of tumors with radiolabeled antibodies against CEA is possible; however, current nuclear medicine scanning cameras rarely detect tumors smaller than 2 cm in diameter. One of the limitations to tumor detection is the inability to place a detecting camera near a deeply seated intra-abdominal tumor. A hand-held gamma-detecting probe, suitable for intraoperative use, was designed to locate radioactive tumors. Experimental work with CEA-producing colon tumor xenografts in nude mice suggests this probe is more sensitive than external scanners in detecting small tumors. A case report documents the clinical use of this new intraoperative probe.

Indium-111-pentetreotide scanning versus conventional imaging techniques for the localization of gastrinoma

BACKGROUND The present study evaluates 111In-pentetreotide scanning as a method for detection of gastrinomas. Operative findings serve as the benchmark for comparison of the efficacy of 111In-pentetreotide versus conventional imaging studies. METHODS Twelve patients (seven female and five male; age, 37 to 80 years) with histologic confirmation of gastrinoma underwent thin section dynamic computed tomography (CT) scanning and 111In-pentetreotide scanning. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 111In-pentetreotide and CT scanning are compared on the basis of tumor size and location. RESULTS Thirty discrete foci of intrahepatic and extrahepatic tumors were detected at operation. CT scanning detected three of nine pancreaticoduodenal lesions, whereas eight of these nine extrahepatic primary tumors were imaged by 111In-pentetreotide scanning. No false-positive 111In-pentetreotide scans were noted. The sensitivity of CT scanning for detection of metastatic disease was 56% versus 94% for the 111In-pentetreotide scan. Successful CT imaging was highly dependent on tumor size. No tumor smaller than 1 cm was imaged by CT, whereas four of seven lesions greater than 1 cm were imaged by 111In-pentetreotide scintigraphy. The smallest gastrinoma imaged by 111In-pentetreotide scanning was a 4 mm duodenal tumor. CONCLUSIONS 111In-pentetreotide scanning was superior to CT scanning for localizing gastrinomas. Further studies are required to determine whether 111In-pentetreotide scans will complement or replace traditional imaging methods.

Localization by hand-held gamma probe of tumor labeled with antibody “cocktail”

Five groups (n = 4) of congenitally athymic female nude mice bearing subcutaneous implants of CX-1 and/or SW-1116 tumor in the hind limbs received iodine-125 radio-labeled monoclonal antibodies (MoAbs) B72.3 (two groups), 17-1A (two groups), and cocktail (one group) (iodogen method, 50 microCi/10 micrograms/mouse). Daily probe counts were made in duplicate with a hand-held detector over each tumor site and the front leg (background) for 21 days. Animals were sacrificed and appropriate well counts were obtained. All the single MoAb preparations localized well in both tumor cell lines. Uptake of monoclonal antibody 17-1A was similar in the two tumor cell lines, with counts initially high and slowly decreasing over the 21-day period. Tumor/background ratios continued to increase over time, indicating that both tumor lines have similar antigenic expression for the monoclonal antibody 17-1A. This was not the case for monoclonal antibody B72.3, which showed a preferential uptake by the CX-1 tumor, with higher initial counts and prolonged binding of the antibody, giving rise to higher tumor/background ratios. The mixture of monoclonal antibodies B72.3 and 17-1A markedly improved the uptake by the CX-1 tumor cell line but not that by the SW-1116 cell line, where the effect was negative when compared to the uptake of the single MoAb preparations. The use of a monoclonal antibody mixture can enhance targeting of some tumor sites. Due to the heterogeneity of tumor cell lines, even within the same animal, different mixtures of monoclonal antibodies are needed to increase the targeting of tumor.

Design and optimization of a breast coil for magnetic resonance imaging

Mathematical methods were implemented to optimize the configuration of specially designed breast coils leading to substantial improvements in magnetic field homogeneity. Multiple-turn shaped coils were constructed according to mathematically determined parameters derived from B1 field optimization calculations. Significant improvements in coil homogeneity were obtained without overcompromising quality factors and signal-to-noise ratios (S/N). Coil performance was verified using both phantom and breast images, revealing improved coil performance particularly in the region adjacent to the chest wall. These new coils are easily constructed and can be designed to accommodate various breast sizes. They can be utilized in the transmit/receive or receive only mode and can be doubly tuned for multinuclear spectroscopic studies. Moreover, nothing precludes their use to image both breasts simultaneously. The results demonstrate the ease of our approach and suggests that these methods can be feasibly applied to other surface coil designs.

Failure of normalized ventricular filling rates to predict true filling rates

Ventricular filling rates derived from radionuclide angiographic (RNA) time–activity curves are commonly expressed as normalized values. The assumption that normalized filling rates have a relationship to the actual filling rates was tested. RNA and contrast angiography were performed within 20 min of one another in 21 patients with widely disparate volumes. The RNA time–activity curve was converted from counts to milliliters by equating the contrast angiography derived end diastolic volume to the end diastolic count rate determined by RNA. Peak filling rates were normalized to end diastolic volume (EDV), stroke volume (SV), and peak ejection rate (ER). No significant correlation between the normalized filling rates and the true filling rate was found. Significant correlations were found between the EDV normalized filling rate and the EDV (r = −0.70) and the ejection fraction (r = 0.89). Normalized filling rates are dependent upon the normalizing variable and are not a pure measure of ventricular filling rates.As the technique of gated radionuclide angiography has matured, it has become apparent that there is more information in the time–activity curve than just the ejection fraction. The emptying rates, filling rates, time to peak emptying, and time to peak filling are parameters that are also available from the time–activity curve. Several authors have used this information to quantitate ventricular ejection and filling rates [1–6]. Since the contrast angiography literature would indicate that in some disease states ventricular filling is impaired [7,8], attempts have been made to identify impaired filling rates by radionuclide techniques. Using this method, decreased normalized filling rates have been found in groups of patients with coronary artery disease and it has been suggested that the observed decrease is due to impairment of active relaxation and/or to reduced compliance [2,3,5,6]. It has even been suggested that the decrease seen in the normalized filling rates may be a reflection of ischemia in the resting patient [6].While these RNA derived parameters have been normalized to end diastolic volume by most authors, normalization to stroke volume and maximum ejection rate have also been.

Iodine-131 labeled anti-CEA antibodies uptake by Hürthle cell carcinoma.

Localization of Hürthle cell cancer deposits in the lung with l-131 labeled anti-carcinoembryonic antigen (CEA) monoclonal antibody is described. This technique may prove useful if conventional scanning with l-131 sodium iodide for distant metastases is negative.

An Assessment of Prolonged Reactivity of Seven Monoclonal Antibodies Against CX-1 Tumor Xenografts Using A Hand-Held Gamma-Detecting Probe

The biodistribution and kinetics of 7 monoclonal antibodies (MAb) with known reactivity against CX-1 tumor were examined over 21 days using a hand-held gamma-detecting probe (Neoprobe system). Twenty-eight immuno-deprived (athymic) nude mice implanted with human colon adenocarcinoma CX-1 xenografts were injected intraperitoneally with 50 microCi of 125I-labeled antibodies (4 mice/antibody). Of the 7 monoclonal antibodies, 4 were anti-CEA (MA, MB, MC, and MD), 2 were anti-TAG 72 (B72.3 NCI and B72.3 fermented) and one was anti-colorectal cancer (17-1A). Daily probe counts were recorded in duplicate over the tumor site and the contralateral nontumor site (background), and tumor-to-background (Tu/Bkg) ratios were calculated. Animals were sacrificed on day 21, and blood, heart, liver, spleen, lungs, kidneys, intestine, muscle, and the tumor were removed for gamma well counting. All antibodies identified the tumor as early as 24 h postinjection and specific tumor localization improved over time. Patterns of prolonged tumor binding varied considerably from one antibody to another, although all but one (MB) showed continuously increasing Tu/Bkg ratios. These data indicate progressive clearance of the antibodies from the background tissue and a persistence of labeled MAb activity in tumor resulting in improved tumor localization with increasing postinjection time.