Academic literature on the topic 'Radioisotopes in endocrinology'

Abstract Background: The 10-yr survival rate of patients with differentiated thyroid cancer exceeds 90%. These patients may be at elevated risk for secondary cancers. Methods: The risk of nonthyroid second primary malignancies after differentiated thyroid cancer was determined in 30,278 patients diagnosed between 1973 and 2002 from centers participating in the National Cancer Institute’s Surveillance, Epidemiology, and End Results program. Median follow-up was 103 months (range, 2–359 months). Risk was further assessed for the addition of radioisotope therapy, gender, latency to development of secondary cancer, and age at thyroid cancer diagnosis. Results: There were 2158 patients who developed a total of 2338 nonthyroid second primary malignancies, significantly more than that expected in the general population [observed/expected (O/E) = 1.09; 95% confidence interval (CI), 1.05–1.14; P < 0.05; absolute excess risk per 10,000 person-years (AER) = 6.39]. A significantly greater risk of second primary malignancies over that expected in the general population was for patients treated with radioisotopes (O/E = 1.20; 95% CI, 1.07–1.33; AER = 11.8) as well as for unirradiated patients (O/E = 1.05; 95% CI, 1.00–1.10; AER = 3.53). However, the increased risk was greater for the irradiated vs. the unirradiated cohort (relative risk = 1.16; 95% CI, 1.05–1.27; P < 0.05). Gender did not affect risk. The greatest risk of second primary cancers occurred within 5 yr of diagnosis and was elevated for younger patients. Conclusions: The overall risk of second primary malignancies is increased for thyroid cancer survivors and varies by radioisotope therapy, latency, and age at diagnosis.

Introduction In contemporary nuclear medicine, alpha, pure beta or beta-gamma emitters are used for targeted therapy. Use of pure and combined alpha/beta emitters in oncology, endocrinology, rheumatology and, a short while ago, interventional cardiology, has refined as an important alternative to more common therapeutic regimens. Two radioisotopes of rhenium, rhenium-186 and rhenium-188, are of particular interest. Production of Rhenium-186 and Rhenium-188 Rhenium-186 is routinely produced in nuclear reactors by direct neutron activation of metallic rhenium enriched with 185Re via 185Re(n,)186Re nuclear reaction. For production of 188Re the target is 186W. 188W is produced by double neutron capture which gives 188Re due to beta decay. Separation of 188Re is performed in generators by column chromatography, extraction or by gel technology. The best results are obtained using chromatographic 188W/188Re generator in which 188W is adsorbed on aluminum. Rhenium-188 is eluted in saline solution. Radiopharmaceuticals labeled with rhenium radioisotopes and their clinical applications There are several fields of applications of radiopharmaceuticals labeled with 186,188Re. For bone pain palliation the most often used are 186Re-HEDP and 188Re-DMSA. For synovectomy, 186Re-sulphide in kit form is already commercially available. Endovascular radiation therapy is performed by using 188Re-perrhenate or 188Re-MAG3. Labeling of peptides and antibodies with 188Re is also reported. Application of rhenium radioisotopes depends on their specific activity. Rhenium-186,188 of low specific activity can be used only for labeling of particles or diphosphonates. However, labeling of peptides or antibodies can be performed only by using 188Re of high specific activity. Conclusion 188Re is expected to have wide applications after development of a chromatographic 188W/188Re generator. One of the advantages of rhenium is its chemical similarity with technetium. So technetium analogues labeled with 186,188Re can be developed for several specific applications.

Iodide (I−) metabolism is crucial for the synthesis of thyroid hormones (THs) in the thyroid and the subsequent action of these hormones in the organism. I−is principally transported by the sodium iodide symporter (NIS) and by the anion exchanger PENDRIN, and recent studies have demonstrated the direct participation of new transporters including anoctamin 1 (ANO1), cystic fibrosis transmembrane conductance regulator (CFTR) and sodium multivitamin transporter (SMVT). Several of these transporters have been found expressed in various tissues, implicating them in I−recycling. New research supports the exciting idea that I−participates as a protective antioxidant and can be oxidized to hypoiodite, a potent oxidant involved in the host defense against microorganisms. This was possibly the original role of I−in biological systems, before the appearance of TH in evolution. I−per se participates in its own regulation, and new evidence indicates that it may be antineoplastic, anti-proliferative and cytotoxic in human cancer. Alterations in the expression of I−transporters are associated with tumor development in a cancer-type-dependent manner and, accordingly, NIS, CFTR and ANO1 have been proposed as tumor markers. Radioactive iodide has been the mainstay adjuvant treatment for thyroid cancer for the last seven decades by virtue of its active transport by NIS. The rapid advancement of techniques that detect radioisotopes, in particular I−, has made NIS a preferred target-specific theranostic agent.

The rates (and extent) of appearance of glucose in arterialized plasma from an oral glucose load and from liver (RaO, RaH) can be estimated in humans using radioisotopes, but estimates vary among laboratories. We investigated the use of stable isotopes and undertook 22 primed intravenous infusions ofd-[6,6-2H2]glucose with an oral load includingd-[13C6]glucose in healthy humans. The effective glucose pool volume (VS) had a lower limit of 230 ml/kg body weight (cf. 130 ml/kg commonly assumed). This VSin Steele’s one-compartment model of glucose kinetics gave a systemic appearance from a 50-g oral glucose load per 70 kg body weight of 96 ± 3% of that ingested, which compared with a theoretical value of ∼95%. Mari’s two-compartment model gave 100 ± 3%. The two models gave practically identical RaOand RaHat each point in time and a plateau in the cumulative RaOwhen absorption was complete. Less than 3% of13C was recycled to [13C3]glucose, suggesting that recycling errors were practically negligible in this study. Causes of variation among laboratories are identified. We conclude that stable isotopes provide a reliable and safe alternative to radioactive isotopes in these studies.

At present there is no clinical guideline or standardised protocol for the treatment of metastatic or invasive phaeochromocytoma and paraganglioma (collectively known as PPGL) due to the rarity of the disease and the lack of prospective studies or extended national databases. Prognosis is mainly determined by genetic predisposition, tumour burden, rate of disease progression, and location of metastases. For patients with progressive or symptomatic disease that is not amenable to surgery, there are various palliative treatment options available. These include localised therapies including radiotherapy, radiofrequency, or cryoablation, as well as liver-directed therapies for those patients with hepatic metastases (e.g., transarterial chemoembolisation) and systemic therapies including chemotherapy or molecular targeted therapies. There is currently intense research interest in the value of radionuclide therapy for neuroendocrine tumours, including phaeochromocytoma and paraganglioma, with either iodine-131 (131I)-radiolabelled metaiodobenzylguanidine or very recently peptide receptor radionuclide therapy (PRRT), and the most important contemporary clinical studies will be highlighted in this review. The studies to date suggest that PRRT may induce major clinical, biochemical, and radiological changes, with 177Lu-DOTATATE being most efficacious and presenting less toxicity than 90Y-DOTATATE. Newer combination therapies with combined radioisotopes, or combinations with chemotherapeutic agents, also look promising. Given the favourable efficacy, logistic, and safety profiles, we believe that PRRT will probably become the standard treatment for inoperable metastatic PPGL in the near future, but we await data from definitive randomised controlled trials to understand its role.

The Caco-2 cell model is widely used to assess the bioaccessibility/availability of iron from foods and diets. Analysis of iron uptake in this human epithelial cell line is usually preceded by a two-step digestion to simulate the conditions in the stomach and small intestine. Moreover, culturing the cells on inserts permits the measurement of iron transport. The cellular iron uptake is determined by direct measurements using radioisotopes, or indirectly by measurement of ferritin, the intracellular storage form of iron. There is a good correlation between Caco-2 cell uptake and human iron bioavailability for a number of dietary factors known to affect iron absorption. However, recent data suggest that in some cases there is no correlation. Possible reasons for such discrepancies, the benefits, and limitations of the Caco-2 cell model are discussed. In conclusion, in vitro experiments with Caco-2 cells are important tools for ranking foods with respect to bioavailability, for mechanistic studies of iron absorption, and for studies of dietary factors influencing absorption. The results need to be confirmed in humans.

Neuroendocrine tumours (NETs) constitute a heterogeneous group of tumours that frequently express cell membrane-specific peptide receptors, such as somatostatin receptors (SSTRs), and of which gastroenteropancreatic (GEP), carcinoid and pancreatic islet cell tumours exhibit the highest expression of SSTRs. Radiolabelled receptor-binding somatostatin analogues (octreotide and lanreotide) act as vehicles to guide radioactivity to tissues expressing SSTRs, and can thus be used for their diagnosis and treatment. After the localization of NETs bearing SSTRs with 111In-octreotide (OctreoScan), a number of radioisotopes with different physical properties have been used for their treatment. The administration of high doses of the Auger electron and γ-emitter 111In-diethylenetriaminepenta-acetic acid (DTPA)0,octreotide in patients with metastatic tumours has been associated with considerable symptomatic improvement but relatively few and short-lived objective tumour responses. The use of another radiolabelled somatostatin analogue coupled with 90Y, a pure β-emitter, 90Y-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA)0,Tyr3,octreotide (90Y-DOTATOC, OctreoTher), was associated with 10–30% objective tumour response rates, and appears to be particularly effective in larger tumours. 111In- and 90Y-DOTA-lanreotide has also been used for the treatment of NETs although its therapeutic efficacy is probably inferior to that of octreotide-based radiopharmaceuticals. More recently, treatment with 177Lu-DOTA0,Tyr3octreotate (177Lu-DOTATATE), which has a higher affinity for the SSTR subtype 2, resulted in approximately 30% complete or partial tumour responses; this radiopharmaceutical is particularly effective in smaller tumours. Furthermore, treatment using both 90Y-DOTATOC and 177Lu-DOTA0,Tyr3octreotate seems promising, as the combination of these radiopharmaceuticals could be effective in tumours bearing both small and large lesions. Tumour regression is positively correlated with a high level of uptake on 111In-octreotide scintigraphy, limited tumour mass and good performance status. In general, better responses have been obtained in GEP tumours than other NETs. The side effects of this form of therapy are relatively few and mild, particularly when kidney-protective agents are used. Treatment with radiolabelled somatostatin analogues presents a promising tool for the management of patients with inoperable or disseminated NETs, and particularly GEP tumours.

Bakgrund: Graves sjukdom är den vanligaste formen av hypertyreos med en incidens på 20 fall per 100 000 individer och år. Graves sjukdom är ett autoimmunt tillstånd där autoantikroppar riktade mot tyreoideastimulerande hormonreceptorer (TSH-R) orsakar okontrollerad syntes och sekretion av tyreoideahormonerna trijodtyronin (T3) och tyroxin (T4). Hur tillståndet uppkommer är inte fullständigt förstått, riskfaktorer inkluderar dock rökning, kvinnligt kön och emotionell stress. Det finns i dagsläget tre etablerade behandlingsmetoder vid Graves sjukdom, dessa är tyreostatikabehandling, radiojodbehandling och tyreoidektomi. Behandling med tyreostatika pågår i regel i 12-18 månader, efter avslutad behandling är risken för recidiv mellan 50-60%. Både tyreoidektomi och radiojodbehandling är definitiva behandlingsmetoder som för majoriteten innebär övergång i hypotyreos med livslångt behov av levotyroxin-(LT4)behandling. Syfte: Syftet med examensarbetet var att undersöka långvarig effekt av radiojodbehandling vid Graves sjukdom och hur radiojodbehandling påverkar livskvalitet. Metod: Arbetet utfördes som en litteraturstudie, en sökning efter kliniska studier gjordes i PubMed med sökorden ”Graves disease” AND ”iodine radioisotopes”. Totalt åtta artiklar som i praktiken baserades på fem studier inkluderades i litteraturstudien. Resultat: Studie 1A, 1B och 1C var uppföljningsstudier av en tidigare utförd randomiserad klinisk studie. I studie 1A sågs det att samtliga individer som behandlats för Graves sjukdom hade sämre livskvalitet än den generella befolkningen 14-21 år efter behandling, ingen skillnad kunde ses beroende på behandlingsmetod. Studie 1B visade att skillnaderna i livskvalitet som funnits i studie 1A inte berodde på tyreoideahormonstatus. Resultaten i studie 1C visade att autoimmun aktivitet i form av tyreoideastimulerande hormonreceptorantikropp(TRAk)-nivåer var förhöjda bland individer som behandlats med radiojod i samtliga fem år som uppföljningen skedde, bland tyreostatika- och kirurgibehandlade individer var TRAk-nivåer normaliserade ett år efter behandling.  Studie 2 visade att tidig insättning av LT4 efter radiojodbehandling kunde förebygga försämring i livskvalitet de sex första månaderna efter radiojodbehandling. I studie 3 sågs det att större andel individer utvecklade oftalmopati efter radiojodbehandling jämfört med tyreostatika, vidare sågs sämre livskvalitet bland individer som utvecklat oftalmopati jämfört med individer utan oftalmopati. Studie 4 eftersökte optimumdosering av radiojod för att uppnå eutyreos bland individer med Graves sjukdom, det fanns att 1,85 MBq/g resulterade i eutyreos hos 72% 12 år efter behandling. I studie 5A sågs det att majoriteten av radiojodbehandlade individer övergick i hypotyreos samt att andelen som upplevde återställning 6-10 år efter diagnostisering var mindre bland de som efter behandling av Graves sjukdom var i behov av LT4-behandling. Studie 5B visade att radiojodbehandlade individer hade sämre livskvalitet jämfört med individer som behandlats med tyreostatika eller kirurgi 6-10 år efter behandling av Graves sjukdom. Vidare hade hela studiepopulationen, oavsett behandlingsmetod, sämre livskvalitet jämfört med den generella populationen. Slutsats: På grund av skillnader i upplägg och utfallsvariabler i de inkluderade studierna kan inga generella slutsatser dras utifrån samtliga studieresultat. Sammantaget sågs dock att individer som behandlats för Graves sjukdom har sämre livskvalitet jämfört med den generella befolkningen många år efter behandling. Det förefaller finnas ökad risk för sämre livskvalitet efter radiojodbehandling av Graves sjukdom jämfört med tyreostatika och tyreoidektomi, det krävs dock fler studier för att säkerställa dessa resultat samt undersöka hur och varför radiojodbehandling påverkar livskvalitet.
Graves´ disease is an autoimmune disease resulting in uncontrolled auto antibody-mediated secretion of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). Graves´ disease is the most common cause of hyperthyroidism and has an annual incidence of 20 cases per 100 000 inhabitants. The pathogenesis of the disease is not yet fully understood, but risk factors include smoking, female gender and emotional stress. Since thyroid hormones act in almost every cell in the body, an imbalance in thyroid hormone levels can lead to severe consequences and affected quality of life. Symptoms of Graves´ disease include weight loss, tremor, tachycardia, heat intolerance, increased sweating, anxiety, fatigue and loss of libido.  There are three established treatment approaches for Graves´ disease including antithyroid drugs, radioiodine treatment and surgical thyroidectomy. The treatment goal for Graves´ disease is to stop the hyperthyroid state and reduce the risk of complications from the condition. Antithyroid drugs is the treatment modality most frequently used in newly diagnosed Graves´ disease and the duration of treatment is normally 12-18 months. The risk of recurrence after antithyroid drugs is 50-60%. Both radioiodine treatment and surgery are considered definitive treatments for Graves´ disease, the majority of treated individuals become hypothyroid with a life-long need for levothyroxine (LT4) treatment. The three available treatment options have both advantages and disadvantages that should be discussed with the patient in each individual case.  The aim of this study was to evaluate the long-term effects of radioiodine treatment for Graves´ disease and how radioiodine treatment affects the quality of life.  This is a literature study based on eight articles that, in practice, were based on five different clinical trials. The included studies were collected from the database PubMed. Since the included studies were different in both study design and outcome, no general conclusion can be drawn from all of the included studies. Two of the studies examined long-term effects on the quality of life of radioiodine treatment for Graves´ disease. Both studies found that persons diagnosed with Graves´ disease have a lower quality of life many years after treatment compared to the general population. The quality of life in individuals treated for Graves´ disease seems to be lower than the general population regardless of thyroid hormone state and mode of treatment. There seems to be an increased risk for lower quality of life among individuals treated with radioiodine compared to antithyroid drugs and surgery. Early administration of LT4 after radioiodine treatment could prevent worsening of quality of life according to the short form health survey (SF-36), whilst the long-term need for LT4 treatment after treatment of Graves´ disease is associated with a lower chance of feeling fully recovered 6-10 years after diagnosis.  There is a need for future studies to determine the effects of radioiodine treatment, especially regarding the long-term quality of life. There is also a need to determine the pathogenesis of Graves´ disease and to find new treatment options for the disease since the established treatment methods result in chronic illness or risk of recurrence.