Strategic Evaluation of the Traceless Staudinger Ligation for Radiolabeling with the Tricarbonyl Core

The traceless Staudinger ligation with its two variants is a powerful biorthogonal conjugation method not only for the connection of biomolecules, but also for the introduction of fluorescence- or radiolabels under mild reaction conditions. Herein, the strategic evaluation of the traceless Staudinger ligation for radiolabeling 99mTc using the fac-[Tc(CO)3]+ core is presented. A convenient and high-yielding three-step synthetic procedure of dipicolylamine-based phosphanols as ligands for the mild radiolabeling was developed. The labeling was accomplished using a tricarbonyl kit and a 99mTc-pertechnetate generator eluate showing 87% radiochemical conversion. The respective rhenium-based, non-radioactive reference compounds were synthesized using (Et4N)2[Re(CO)3Br3] as precursor. All products were analyzed by NMR, MS, and elemental analysis. Additional XRD analyses were performed.

Clinical Significance of Extra-Thyroid99mTc-Pertechnetate Uptake Before Initial Radioiodine Therapy For Differentiated Thyroid Carcinoma

Background: Over the last few decades, extra-thyroid 99mTc-pertechnetate uptake has rarely been reported. The clinical characteristics of extra-thyroid 99mTc-pertechnetate uptake were retrospectively analysed to explore the effect of the phenomenon on RAI therapy for DTC and its clinical significance. Methods: In this study, we retrospectively analysed 4930 RAI-treated DTC patients who had undergone 99mTc-pertechnetate scanning. Thirty-eight cases with extra-thyroid 99mTc-pertechnetate uptake were selected. The clinical features, location, location count and extra-thyroid 99mTc-pertechnetate uptake distribution were analysed, combined with the uptake rate, stimulated thyroglobulin (sTg) level, post-therapy whole-body scan and curative effect. Results: The results showed that sixty-five extra-thyroid 99mTc-pertechnetate foci were detected in 38 patients. The proportions of patients with abnormal uptake in the lymph nodes, lungs and bones were 68.4%, 10.5% and 10.5%, respectively. The corresponding uptake rates were 0.2%, 0.2% and 0.8%. The uptake rate was significantly lower in the lymph nodes than in the bones (Z = -2.722, p = 0.019). The uptake rate and sTg were positively correlated (r = 0.36, p = 0.027). 131I uptake was found in 36 cases at the technetium uptake site, and the number of iodine uptake foci was significantly higher than that of 99mTc-pertechnetate uptake foci. The sTg value and pathological staging significantly differed between the excellent and nonexcellent response groups (Z = 2.947, p = 0.003 and Z = 2.348, p = 0.019, respectively). Conclude: Extra-thyroid 99mTc-pertechnetate uptake mostly indicated metastases with specific clinical features, which may have prognostic value for the judgment of iodine uptake function and the RAI therapy plan.

Thyroid scintigraphy in diagnosis of nodular and diffuse thyroid pathology

Diagnosis of the causes of thyrotoxicosis (destruction or increased functional activity of the thyroid tissue in nodular and diffuse thyroid pathology) is a key point in determining the management of patients with this pathology. Scintigraphy is the method of choice in differential diagnosis of the causes of thyrotoxicosis assessing the functional state of the thyroid gland. According to variable medical interest, thyroid scintigraphy can be performed using 99mTc-pertechnetate or radioactive iodine isotopes (123I, 124I, 131I). For thyroid uptake evaluation used scintigraphy with 99mTc-pertechnetate radiopharmaceutical, which is not organificates and quickly excretes from thyroid tissue. In case of thyroid iodine pharmacokinetics investigation radiopharmaceuticals labeled by iodine isotopes (123I,131I, 124I) are used. The review includes original scintigrams, tables and diagrams. Article shows thyroid scintigraphy informativity analysis, evaluates the place and role of the thyroid scintigraphy examinations in modern diagnostic algorithms taking into account the history of the disease, laboratory tests, ultrasound (TIRADS) and result ofFNA (Bethesda). Additionally authors focused on existing clinical guidelines analysis. An optimized algorithm for the diagnosis and treatment of diffuse and/or nodular thyroid pathology associated with thyrotoxicosis is proposed.

Protective Effect of Alpha-Lipoic Acid on Salivary Dysfunction in a Mouse Model of Radioiodine Therapy-Induced Sialoadenitis

Radioiodine (RI) therapy is known to cause salivary gland (SG) dysfunction. The effects of antioxidants on RI-induced SG damage have not been well described. This study was performed to investigate the radioprotective effects of alpha lipoic acid (ALA) administered prior to RI therapy in a mouse model of RI-induced sialadenitis. Four-week-old female C57BL/6 mice were divided into four groups (n = 10 per group): group I, normal control; group II, ALA alone (100 mg/kg); group III, RI alone (0.01 mCi/g body weight, orally); and group IV, ALA + RI (ALA at 100 mg/kg, 24 h and 30 min before RI exposure at 0.01 mCi/g body weight). The animals in these groups were divided into two subgroups and euthanized at 30 or 90 days post-RI treatment. Changes in salivary 99mTc pertechnetate uptake and excretion were tracked by single-photon emission computed tomography. Salivary histological examinations and TUNEL assays were performed. The 99mTc pertechnetate excretion level recovered in the ALA treatment group. Salivary epithelial (aquaporin 5) cells of the ALA + RI group were protected from RI damage. The ALA + RI group exhibited more mucin-containing parenchyma and less fibrotic tissues than the RI only group. Fewer apoptotic cells were observed in the ALA + RI group compared to the RI only group. Pretreatment with ALA before RI therapy is potentially beneficial in protecting against RI-induced salivary dysfunction.

RADIOISOTOPE DIAGNOSTIC ALGORITHM FOR THE RELAPSE AND METASTASES DETECTION IN THE IODINE-NEGATIVE DIFFERENTIATED THYROID CANCER

Objective. Developing of algorithm for the post-surgical management of patients with iodine-negative metastases of differentiated thyroid cancer (DTC). Materials and methods. The DTC patients with iodine-negative metastases (n = 115) were enrolled in the study. Of them the whole body scintigraphy (WBS) was performed with technetium-99m-hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) (n = 30), WBS with technetium-99m dimercaptosuccinic acid (99mTc-DMSA) (n = 30), 18FDG PET (n = 30), and computer tomography (CT-scan) (n = 25). Complex 99mTc-pertechnetate scans including the dynamic and static scintigraphy was performed supplementary to 99mTc-MIBI WBS in 10 patients to obtain the angiographic curves from DTC metastatic foci. The non-radioiodine radiopharmaceutical technologies, namely the labeled 99mTc-MIBI, 99mTc-DMSA, 99mTc-pertechnetate, and 18FDG were applied to detect the iodine-negative DTC metastases. Radioisotopic examinations were performed at the dual-head gamma camera (Mediso Medical Imaging Systems Ltd., Hungary) and single photonemission computed tomography (SPECT) scanner «E.CAM» (Siemens, Germany). PET/CT scans were performed on the «Biograph 64 TruePoint» imaging platform (Siemens, Germany) in accordance with the European Association of Nuclear Medicine (EANM) recommendations for the Siemens imaging devices with 3D-mode data acquisition. Results. The conducted research suggested that it is feasible to use the non-radioiodine (99mTc-MIBI and 99mTc-DMSA) radiopharmaceutical technologies to detect the iodine-negative DTC metastases. 18FDG PET is a highly informative technology for the detection of iodine-negative DTC metastases in case of lung involvement in the process. Compare of the non-radioiodine radiopharmaceuticals, CT scan and 18FDG-PET/CT indicated the highest sensitivity of 18FDG PET/CT (p < 0.05). WBS with 99mTc-MIBI and 99mTc-DMSA featured the highest specificity (100 %, p < 0.05). X-ray CT is marked by the significantly lower either sensitivity, specificity, and accuracy rate (p > 0.05). Developing and application of algorithm for the post-surgical management of patients with iodine-negative forms of DTC will allow for the betimes detection of relapses and metastases with administration of adequate surgical, radiation, and targeted treatment. Conclusions. Obtained results offer the opportunity to optimize the post-surgical management of patients with iodine-negative DTC forms using the options of radionuclide diagnostics with non-radioiodine radiopharmaceuticals. The latter are readily available providing the cost-cutting of diagnostic support in these patients. Place of morphological methods of diagnosis is determined and stage of monitoring of patients with the iodine-negative metastases is established. Possibility of the 18FDG-PET tests for the early diagnosis of iodine-negative metastases in DTC for the first time have been studied and substantiated in Ukraine. A comprehensive radiation algorithm for the long-term monitoring of this category of patients will allow the timely detection of recurrences and metastases of DTC and appropriate surgery, radiation and targeted therapy administration. Data obtained as a result of the study allowed to improve the overall and recurrence-free survival rates in the able-bodied DTC patients and reduce the costs of follow-up of patients with iodine-negative forms of DTC. Key words: differentiated thyroid cancer, radioiodine-negative metastases, non-radioiodine radiopharmaceuticals, 18FDG-PET/CT.