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The new technology of combined transmission and emission tomography in evaluation of endocrine neoplasms.

UNLABELLED: The clinical value of a novel technology of combined transmission and emission tomography (TET) was assessed in patients with endocrine tumors. METHODS: TET technology, which combines simultaneous acquisition of SPECT and CT images, using the same imaging device, allows correct fusion of images of both modalities. TET was performed on 27 patients with known or suspected endocrine tumors. The radiopharmaceuticals used for the emission part of the study were chosen according to the tumor type: (111)In-octreotide for patients with neuroendocrine tumors (n = 10), (99m)Tc-sestamibi for patients with primary hyperparathyroidism (n = 8), (131)I for patients with thyroid cancer (n = 4), and (123)I-metaiodobenzylguanidine and (75)Se-cholesterol for patients with adrenal masses (n = 3 and n = 2, respectively). The additional information provided by TET compared with scintigraphy was assessed for both image interpretation and clinical utility. RESULTS: TET did not provide any additional data in 16 patients (59%), including 5 patients with normal scintigraphy. In 11 patients (41%) with abnormal SPECT findings, TET improved image interpretation by providing a better anatomic localization of SPECT-detected lesions. It showed unsuspected bone involvement in 4 patients, it identified the organs involved and the relationship of the lesions to neighboring structures in 5 patients, and it differentiated physiologic uptake from tumor uptake in 2 patients. TET provided additional information of clinical value in 9 patients (33%). It assisted in better planning of surgery in 2 patients with neuroendocrine tumors and in 2 patients with ectopic parathyroid adenomas. It changed the treatment approach in 2 patients with neuroendocrine tumors and 1 patient with thyroid carcinoma, and it altered prognosis in 2 patients with thyroid malignancy. CONCLUSION: TET enhances the already unique role of nuclear medicine procedures in the assessment and management of patients with endocrine neoplasms.

3-Iodobenzylguanidine↗

Pharmacokinetics of internally labeled monoclonal antibodies as a gold standard: comparison of biodistribution of 75Se-, 111In-, and 125I-labeled monoclonal antibodies in osteogenic sarcoma xenografts in nude mice.

In order to know the true biodistribution of anti-tumor monoclonal antibodies, three monoclonal antibodies (OST6, OST7, and OST15) against human osteosarcoma and control antibody were internally labeled with 75Se by incubating [75Se]methionine and hybridoma cells. 75Se-labeled monoclonal antibodies were evaluated both in vitro and in vivo using the human osteogenic sarcoma cell line KT005, and the results were compared with those of 125I- and 111In-labeled antibodies. 75Se-, 125I- and 111In-labeled monoclonal antibodies had identical binding activities to KT005 cells, and the immunoreactivity was in the decreasing order of OST6, OST7, and OST15. On the contrary, in vivo tumor uptake (% injected dose/g) of 75Se- and 125I-labeled antibodies assessed using nude mice bearing human osteosarcoma KT005 was in the order of OST7, OST6, and OST15. In the case of 111In, the order was OST6, OST7, and OST15. High liver uptake was similarly seen with 75Se- and 111In-labeled antibodies, whereas 125I-labeled antibodies showed the lowest tumor and liver uptake. These data indicate that tumor targeting of antibody conjugates are not always predictable from cell binding studies due to the difference of blood clearance of labeled antibodies. Furthermore, biodistribution of both 111In- and 125I-labeled antibodies are not identical with internally labeled antibody. Admitting that internally labeled antibody is a "gold standard" of biodistribution of monoclonal antibody, high liver uptake of 111In-radiolabeled antibodies may be inherent to antibodies. Little, if any, increase in tumor-to-normal tissue ratios of antibody conjugates will be expected compared to those of 111In-labeled antibodies if stably coupled conjugates are administered i.v.

Animals↗

Selenium-75: a potential source for use in high-activity brachytherapy irradiators.

A study was made to find a high-specific-activity radioisotope having a longer half-life and lower gamma-ray energies than 192Ir in order to replace 192Ir in high-activity afterloading brachytherapy devices. Based upon a number of considerations, 75Se was selected. The present paper describes the physical properties of 75Se, its method of production, and the properties of an encapsulated source that was fabricated to prove the accuracy of our initial calculations.

Biophysical Phenomena↗

Direct measurement of first-pass ileal clearance of a bile acid in humans.

The purpose of this study was to develop and validate a method of directly measuring ileal bile acid absorption efficiency during a single enterohepatic cycle (first-pass ileal clearance). This has become feasible for the first time because of the availability of the synthetic gamma-labeled bile acid 75Selena-homocholic acid-taurine (75SeHCAT). Together with the corresponding natural bile acid cholic acid-taurine (labeled with 14C), SeHCAT was infused distal to an occluding balloon situated beyond the ampulla of Vater in six healthy subjects. Completion of a single enterohepatic cycle was assessed by obtaining a plateau for 75SeHCAT activity proximal to the occluding balloon, which prevented further cycles. Unabsorbed 75SeHCAT was collected after total gut washout, which was administered distal to the occluding balloon. 75SeHCAT activity in the rectal effluent measured by gamma counter was compared with that of absorbed 75SeHCAT level measured by gamma camera and was used to calculate first-pass ileal clearance. This was very efficient (mean value, 96%) and showed very little variation in the six subjects studied (range, 95%-97%). A parallel time-activity course in hepatic bile for 14C and 75Se during a single enterohepatic cycle, together with a ratio of unity for 14C/75Se in samples obtained at different time intervals, suggests that 75SeHCAT is handled by the ileum like the natural bile acid cholic acid-taurine. Extrapolation of 75SeHCAT first-pass ileal clearance to that of the natural bile acid therefore seems justifiable. In a subsidiary experiment, ileal absorption efficiency per day for 75SeHCAT was also measured by scanning the gallbladder area on 5 successive days after the measurement of first-pass ileal clearance. In contrast with absorption efficiency per cycle, absorption efficiency per day varied widely (49%-86%), implying a possible wide variation in recycling frequency per day.

Adult↗

Generic models for radionuclide dosimetry: 11C-, 18F- or 75Se-labelled amino acids.

A generic biokinetic model was developed for use in the assessment of the internal dose received by human subjects injected with amino acids labelled with 11C (T1/2 = 0.34 h, beta+, gamma), 18F(T1/2 = 1.83 h, beta+, gamma) or 75Se (T1/2 = 119.8 d, beta-, gamma). This generic model was used in conjunction with the MIRDOSE 3 computer programme to calculate radiation doses to adults; these radiation doses were compared with those calculated using compound-specific models for two [11C]-, and eight [18F]-labelled amino acids and [75Se]selenomethionine. In general, the effective doses, as well as the organ and tissue doses, calculated using the generic model agreed within a factor of 2 or less, with those calculated using compound-specific models; the generic model tended to over-, rather than underestimate the organ and tissue doses. It was concluded that for 11C- and 18F-labelled amino acids and for 75Se-labelled amino acids or their analogues, the single generic biokinetic model could be applied for general radiation protection purposes.

Adult↗

Scintigraphic study of extra-adrenal ganglioneuroma in a patient with overlap between multiple endocrine neoplasia types 1 and 2.

A 27-year-old woman was diagnosed with a pituitary prolactinoma. Seven years later, when she was 34, an abdominal mass was incidentally discovered and ascribed to the right adrenal gland on the basis of evidence from ultrasonography, computed tomography, and arteriography. Adrenal scintigraphy with Se-75 selenomethylcholesterol imaged both adrenal glands, but the right gland was distorted, suggesting external compression. I-131 MIBG was not taken up by the mass. At surgery, an extra-adrenal ganglioneuroma was found and excised. This case represents an overlap between multiple endocrine neoplasia types 1 and 2. The failure of the ganglioneuroma to concentrate MIBG was likely caused by secretory inactivity of a biologically mature tumor.

3-Iodobenzylguanidine↗

[Scintigraphic characterization of expansive lesions located in the adrenals. Comparison with magnetic resonance imaging].

In this study, 35 patients (11 men and 24 women, mean age 47 +/- 16 years) with unilateral adrenal masses underwent nor-cholesterol (nor-Chol) (n = 11), metaiodobenzylguanidine (MIBG) (n = 15) or nor-Chol and MIBG (n = 9) radionuclide studies. In all patients Magnetic Resonance (MR) adrenal imaging was also performed. In 19 (54%) patients, no laboratory abnormalities of adrenal function were observed. In the other 16 (46%) patients, adrenal hyperfunction was found. In 21 lesions, histology showed 10 pheochromocytomas (Pheos), 6 adenomas, 3 metastases, 1 cyst and 1 nodular focal liver hyperplasia. In the remaining 14 lesions, increased cortisol (n = 4) or aldosterone (n = 2) levels and/or intense nor-Chol uptake (n = 14) were considered suggestive of adenoma. Diagnostic accuracy of both nor-Chol and MIBG radionuclide studies in correctly identifying adenoma or Pheos was 100%. Conversely, qualitative MR signal intensity (SI) analysis on T2-weighted images did not allow to accurately distinguish lesions of different nature. In particular, 10 Pheos, 8 adenomas, 3 mestastasis and 1 cyst clearly showed on T2-weighted images higher SI than the liver; 5 adenomas had a slight higher SI; the remaining lesions (7 adenomas and 1 liver hyperplasia) exhibited low SI. In conclusion, adrenal scintigraphy using nor-Chol or MIBG allows to identify adenomas and Pheos, respectively. Conversely, qualitative MR SI analysis cannot differentiate different adrenal lesion (Pheos, adenoma, metastasis and cyst) and yields heterogeneous results in adenomas.

3-Iodobenzylguanidine↗

A comparison of the uptake of [75Se]selenite, [75Se]selenomethionine and [35S]methionine by tissues of ewes and lambs.

The fate of selenium, given as Na2(75)SeO3, or [75Se]selenomethionine, and of [35S]methionine administered intravenously to ewes and lambs, has been examined. The main intention was to follow the incorporation of selenium into protein in a number of tissues, including liver and kidney, and to measure the extent of that incorporation of selenoamino acid, particularly with respect to the administration of selenite. The ewes chosen were lactating ewes with lambs at foot, and the lambs were animals which had been weaned on to fodder low in selenium and were recovering from white muscle disease with selenium therapy. These two experimental situations were chosen as they offered conditions under which selenium incorporation might be considered to be maximal. Entry of isotope into milk was rapid and was greater when 75Se was given as the selenoamino acid than as selenite. In both ewes and lambs greater amounts of activity, derived from selenite, were bound to plasma proteins than to the proteins of milk. This was particularly evident in samples taken some hours after administration. This ability of the plasma to bind selenium was demonstrated by alkaline dialysis. Small, though significant amounts of selenium, derived from Na2(75)SeO3, were incorporated as selenoamino acids into the proteins of liver, kidney and pancreas, as well as into the proteins of milk and plasma. In ewes, both selenomethionine and selenocystine were identified chromatographically in enzyme digests of defatted liver and kidney. Some differences occurred in the distribution of labelled compounds in organs from lactating ewes and recovering lambs. The incorporation of selenium into protein is discussed briefly in relation to the recent findings of an association between selenium and the enzyme glutathione peroxidase.

Animals↗