Kinetics of Perrhenate Uptake and Comparative Biodistribution of Perrhenate, Pertechnetate, and Iodide by Nai Symporter-Expressing Tissues in Vivo

Pertechnetate (as (TcO4-)-Tc-99m), I-123(-), and I-131(-) have a long and successful history of use in the diagnosis and therapy of thyroid cancer, with uptake into thyroid tissue mediated by the sodium-iodide symporter ( NIS). NIS has also emerged as a potential target for radiotherapy of nonthyroid malignancies that express the endogenous or transfected symporter. Perrhenates (as (ReO4-)-Re-188 and ( ReO4-)-Re-186) are promising therapeutic substrates of NIS, although less is known about their behavior in vivo. In this study, we endeavored to characterize the biologic behavior of perrhenate, especially in relation to iodide and pertechnetate, to better explore its possible therapeutic role. Methods: We describe the simultaneous biodistribution and uptake in vivo of iodide, pertechnetate, and perrhenate in groups of healthy CD1 mice, either with or without coadministration of perchlorate (ClO4-), a potent NIS inhibitor . Animals administered single radiopharmaceuticals were imaged as a means of illustrating these findings. Kinetic properties of perrhenate were compared with those of iodide in a stably transfected NIS-bearing Madin- Darby canine kidney (MDCK) cell line. Results: Biodistributions of iodide, pertechnetate, and perrhenate in live mice were remarkably similar. Activity in salivary gland and stomach was severalfold greater than in blood, remained elevated over the initial 2 h, and subsequently washed out . A similar pattern characterized pertechnetate and perrhenate uptake by the thyroid, in which the 2-h concentration was slightly more elevated than at the 20-min time point. However, uptake subsequently decreased by 19 h. In contrast, iodide continued to increase through the 19-h time point, presumably as a result of organification. The addition of perchlorate sharply decreased uptake of all 3 radiopharmaceuticals by the stomach, salivary glands, and thyroid and resulted in their rapid clearance, paralleling blood-pool clearance. In tissues that do not express NIS ( liver, muscle, spleen), uptake of all 3 radiopharmaceuticals was low and rapidly decreased over time, paralleling blood- pool clearance. Similar findings were seen in kidney, where only minimal amounts of NIS are expressed in tubular cells. In stably transfected MDCK cells, steady-state accumulation of iodide was approximately 4-fold higher than that of perrhenate at 30 min. No active transport was demonstrated in nontransfected MDCK cell lines or after perchlorate administration. Uptake values measured at different concentrations of substrate demonstrated saturation kinetics . Apparent maximal velocity values for perrhenate and iodide were 25.6 1.4 and 106 3.2 pmol/mug, respectively, and corresponding affinity constant values were 4.06 0.87 and 24 .6 1.81 mumol/L. Conclusion: Perrhenate is avidly taken up by NIS in a manner similar to iodide and pertechnetate in vivo, with the exception of organification of iodide by the thyroid. By more fully appreciating the behavior of perrhenate, especially in relation to iodide and pertechnetate , we can better realize its potential role in the diagnosis and therapy of NIS-bearing tissues

Pulmonary Scintigraphy for the Diagnosis of Acute Pulmonary Embolism: A Survey of Current Practices in Australia, Canada, and France.

International audienceThere are currently no data published regarding the proportion of nuclear medicine centers using SPECT or SPECT/CT rather than planar ventilation/perfusion (V/Q) imaging in patients with suspected acute pulmonary embolism (PE). Furthermore, the reporting criteria used for interpretation of both planar and SPECT V/Q scans are variable and data are lacking regarding which criteria are commonly used in various centers. The aim of this study was to assess current practices regarding the performance and interpretation of lung scintigraphy across 3 different countries. A short online survey composed of simple multiple-choice questions was distributed to nuclear medicine departments in Australia, Canada, and France during the period April to December 2014. The survey covered image acquisition, interpretation criteria for SPECT and planar images, and use of pseudoplanar images and radiopharmaceuticals. Information was initially solicited by 2 sets of e-mails, which pointed to the survey internet link. Departments were subsequently contacted by telephone. A single response per department was consolidated. Three hundred thirty-one responses were collected (Australia, 74; Canada, 48; and France, 209). Twenty-eight percent of centers indicated use of V/Q planar imaging alone whereas 72% of centers included some form of SPECT in their acquisition protocol for evaluation of PE, specifically V/Q SPECT in 36%, V/Q SPECT/CT in 29%, Q SPECT/CT in 2%, and both V/Q planar and SPECT in 5%, with a strong variability among countries. The most commonly used criteria for SPECT interpretation were the those of the European Association of Nuclear Medicine (60%). Criteria used for planar interpretation were heterogeneous (European Association of Nuclear Medicine criteria, 35%; Prospective Investigation of Pulmonary Embolism Diagnosis study, 29%; no standardized criteria, 21%). Sixty-three percent of departments used pseudoplanar images in addition to SPECT images. In the 3 countries surveyed, SPECT has largely replaced planar imaging for evaluation of PE, with almost half of the SPECT studies incorporating a CT acquisition. Criteria used for interpretation are inconsistent, especially for planar imaging