Potential organ or tumor imaging agents. 16. Fluorinated androstanes and the prostate.

A series of substituted 5alpha-androstan-17beta-ols was synthesized and evaluated for their potential use in the development of a prostate imaging agent. The ability of the synthesized compounds to compete with [3H]-5alpha-dihydrotestosterone for rat prostate androgen receptor protein served as the screening assay. For 3-substituted derivatives, the order of binding to the androgen receptor protein was =O greater than -OH greater than H approximately or equal to F. 3beta-Fluoro-5alpha-androstan-17beta-ol was found to have approximately 5% the androgenic activity of testosterone propionate in the castrated rat. The low biological activity for the 3beta-fluoro derivatives, coupled with the synthetic obstacles associated with introducing fluorine-18, has led us to search for more suitable halo steroids as potential radiodiagnostics.

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.

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.

The influence of venous occlusion on xenon 133 muscle clearance.

Progressive degrees of venous occlusion in the canine hind limb were employed to evaluate the influence of venous disease on the xenon 133 muscle washout test. Increasing degrees of venous occlusion, from superficial venous occlusion alone to total occlusion induced with intravenously administered thrombin, decreased both resting muscle blood flow and maximal muscle blood flow stimulated with intra-arterially administered papaverine hydrochloride. This alteration lasted for varying lengths of time with all but the group with total venous occlusion eventually returning to a normal flow. The status of the venous circulation must be considered in order to accurately interpret the results of the 133Xe clearance test when used to evaluate arterial occlusive disease. The 133Xe washout test may be an accurate indicator of venous occlusion in a limb with normal arterial supply.

The inhibitive effects of steroid analogues in the binding of tritiated 5alpha-dihydrotestosterone to receptor proteins from rat prostate tissue.

The relationship between molecular structure and the binding potential of steroids to receptor proteins was investigated. Twenty-four selected steroids were studied in minced incubations of rat prostate tissue. Measurements of the inhibitory effects of the steroids on the binding of tritiated 5alpha-dihydrotestosterone to the receptor proteins were obtained in the 100,000 times g dialysed supernatant and the purified nuclear component of the prostate cells. The steroids that achieved the highest degree of inhibition were those compounds that exhibited a generally planar geometric shape and were known to possess potent androgenic activity. Several of the compounds were shown to possess a higher degree of inhibition than that of testosterone or 5alpha-dihydrotestosterone. The data is further supportive of the two step theory that necessitates the complexing of the free steroids to the receptor proteins in the cytosol before transport to the nuclei. Evidence is also suggestive of the presence of 17-esterase activity. The inhibitory effect of the steroids apparently involves the binding to the intracellular receptors and is not related to the uptake of 5alpha-dihydrotestosterone into the cell.

Androgen receptor protein binding properties and tissue distribution of 2-selena-a-nor-5alpha-androstan-17beta-ol in the rat.

2-selena-A-nor-5alpha-androstan-17beta-ol was studied in vitro and in vivo in the rat prostate gland. The data demonstrates the ability of this compound to selectively complex with the specific receptors of 5alpha-dihydrotestosterone (5alpha-DHT) in the cytosol and to be retained in the nuclei in an unaltered form. Studies with selenium-75 labeled material suggests that the uptake and localization is similar to endogenous 5alpha-dihydrotestosterone.

Benign histiocytoma (xanthoma) of the rib.

A 64-year-old man was found to have isolated focal rib lesion(s) by radiographs and radionuclide bone scan. A biopsy of one of the lesions located by imaging was done. The histologic diagnosis was sclerosing (ossifying) xanthoma. A literature search disclosed that xanthomatous lesions of bone are only one of the manifestations in hyperlipidemic patients. These benign lesions should be included among the causes of discrete hot rib abnormalities visualized on bone scan.

Atypical findings of discordant bone scan and radiographs in transient osteoporosis of the hip: case report and review of the literature.

The authors report atypical findings of discordant bone scans and radiography seen in a patient with transient osteoporosis of the hip (TOH). Presented in the case of a 60-year-old man who had spontaneous onset of left hip pain which worsened for 2 months with weight-bearing on the affected side. Initial and follow-up radiographs of the let hip were normal. Bone scan demonstrated intense uptake of Tc-99m MDP in the affected femoral head and neck, corresponding to characteristics of abnormal signal intensity of TOH or transient bone marrow edema syndrome on MRI. This discordant pattern of bone scan and radiographs has rarely been reported in the literature. Its possible mechanism of causation and clinical implication in TOH, together with a review of the literature, are discussed in this report.

Metastatic pure papillary thyroid carcinoma presenting as a toxic hot nodule.

In the majority of cases, carcinoma of the thyroid presents as a cold nodule by radioiodine and Tc-99m sodium pertechnetate scintigraphy. Whereas the presence of a hot nodule usually implies a benign entity, it does not provide complete assurance against thyroid malignancy. Presented is a rare case of metastatic pure papillary thyroid carcinoma appearing as a hot nodule on Tc-99m sodium pertechnetate and I-123 sodium iodide scintigraphy. The implications of such a case, its management, and review of the pertinent literature are discussed.

Confusing appearance of a dilated jejunal loop.

A case report is presented concerning a patient with a dilated loop of bowel that was misinterpreted on ultrasound examination. Attention is called to this entity as part of the differential diagnosis of an intra-abdominal fluid collection demonstrated by ultrasound.

133Xe muscle clearance: a screening test for arterial occlusive disease.

133Xe muscle clearance following ischemic exercise provides a simple, well-tolerated screening procedure for evaluating patients suspected of having arterial occlusive disease in the lower extremeties and may be useful in the follow-up of patients who have undergone corrective arterial surgery. It can be performed in nuclear medicine units capable of doing renography, and the authors feel it should be used prior to undertaking more invasive procedures such as arteriography. Methods and results of tests involding 92 legs in men are described.