Indium-111-labelled octreotide scintigraphy in the diagnosis and management of non-iodine avid metastatic carcinoma of the thyroid

Indium-111-labelled octreotide scintigraphy in the diagnosis and management of non-iodine avid metastatic carcinoma of the thyroid. Treatment of differentiated thyroid cancer is a success of modern medicine with the use of radioiodine (I-131). However, a significant proportion of thyroid cancers may be non-iodine avid. Thyroid tumours are known to express somatostatin receptors. Octreotide, an analogue of somatostatin, can be combined with a radioactive isotope, such as In-111-DTPA(0) to visualise tumours with high concentrations of somatostatin receptors. We assessed 18 patients with histologically proven metastatic or locally recurrent noniodine avid thyroid carcinoma to determine the usefulness of In-111-DTPA(0) octreotide scintigraphy compared to conventional radiology in diagnosing sites of metastasis. The diagnosis of metastatic disease was made using conventional radiology and all had prospective scintigraphy using In-111-DTPA(0) octreotide. Of the 18 patients, 14 had octreotide-positive scans. In eight, the octreotide scans identified the same sites of metastases as conventional radiology, that is, were concordant. In nine patients, conventional radiology showed more extensive disease than revealed on the octreotide scans. In one patient with widespread bone metastases, octreotide gave a more detailed assessment of metastatic disease than conventional radiology. These data indicate that In-111-DTPA(0) octreotide imaging for patients with non-iodine avid carcinoma of the thyroid may be a useful diagnostic and staging tool. One patient with Hurthle cell carcinoma metastatic to bone and a positive octreotide scan has been treated with (90)yttrium-labelled octreotide

Interaction of a G protein with an activated receptor opens the interdomain interface in the alpha subunit

In G-protein signaling, an activated receptor catalyzes GDP/GTP exchange on the Gα subunit of a heterotrimeric G protein. In an initial step, receptor interaction with Gα acts to allosterically trigger GDP release from a binding site located between the nucleotide binding domain and a helical domain, but the molecular mechanism is unknown. In this study, site-directed spin labeling and double electron–electron resonance spectroscopy are employed to reveal a large-scale separation of the domains that provides a direct pathway for nucleotide escape. Cross-linking studies show that the domain separation is required for receptor enhancement of nucleotide exchange rates. The interdomain opening is coupled to receptor binding via the C-terminal helix of Gα, the extension of which is a high-affinity receptor binding element