European Nuclear Medicine Guide
Iodide uptake by the thyroid cells results from active transport mediated by the sodium iodide symporter (NIS). Iodide is translocated into the colloid, oxidized and then combined with the tyrosine residues of thyroglobulin. Such reaction is stimulated by thyrotropin levels. Iodide is also taken up by other tissues (e.g. salivary gland) but its organification is not possible. Thus, there is no prolonged retention of iodine outside thyroid gland or DTC metastases. Kidneys are the principal pathway for iodine elimination and renal excretion is rapid in the first hours, reaching a plateau within 24 to 48 hours. Such a clearance is not influenced by iodine intake but by the endogenous TSH levels.
Differentiated Thyroid cancer (DTC)
Suspicious DTC persistence/relapse on the base of Thyroglobulin levels in patients already treated with thyroidectomy and radioactive iodine therapy (RAI).
Identification of DTC patients amenable for second RAI
Dosimetric pretherapeutic studies (i.e. pre 131I)
Pregnancy and lactation.
Relative contraindications: absence of TSH stimulation (i.e. exogenous or endogenous) and Iodine contamination (e.g. drugs containing high concentration of iodine, as Amiodarone, or iodine-based contrast material for radiological investigations).
No adverse reactions are reported in literature. Overall, the safety profile of 124I is very good and no safety concern requiring additional risk minimisation activities have been identified.
Activity to administer: 20-185 MBq oral or intravenously
Diagnostic purpose: patients with suspicious DTC persistence/relapse.
Dosimetric purpose: patients amenable for RAI with curative intent in which dosimetric study is indicated (e.g. paediatric patients, young adults, multi-treated patients).
Since 124I has both a diagnostic and dosimetric role, patients have to be in the same clinical condition expected before 131I administration. Therefore, hypothyroidism condition, after withdrawal of thyroid hormone (THW) for 3-4 weeks (TSH level of at least 30 mIU/L) and 4 weeks of hypoiodic diet [148]. However, NIS stimulation by using rhTSH is an important e reliable alternative. Iodine contamination should be checked by urine testing. During THW, patients may experience hypothyroid symptoms such as fatigue, listlessness, depression and concentration disorders. Extra hydration and timely voiding are widely recommended after injection to facilitate clearance of residual tracer and to lessen the dose to bladder wall. Any drug the patient is taking has to be reported to the nuclear medicine physician, in order to discuss its possible temporary suspension.
Relatively low activities of 20–74 MBq (up to 185 MBq) are used for diagnostic purposes. The preferred 124I route of administration is oral. Safety of efficacy problems are not expected as the doses applied are in the range of nanograms.
Whole body 124I-PET/CT can be acquired by using a 5-point protocol (4, 24, 48, 72, and 96 h after 124I administration) that is certainly the most accurate among the approaches investigated. However, the adapted 24-96-h approach using 2 points is an optimal dosimetry protocol when the clinical workload is particularly heavy, reducing logistical and time demands for patients [337].
The goal of individualized 124I-PET/CT dosimetry is to deliver ample radiation doses to destroy DTC foci, without exceeding safe doses to the whole body, particularly the bone marrow and lungs, which are the main concerning organs at risk in this clinical iter.
Statistical results highlighted that the pre-therapeutic blood kinetics derived from diagnostic 124I activities provides a reliable estimation of the intra-therapeutic 131I blood kinetics in patients receiving largely high therapy activities, showing its potential for radioiodine treatment planning [338,339].
Thyroid lesions dosimetry can be easily performed by acquiring 124I-PET/CT images at different time. The lowest doses able to provide therapeutic effects are 300 Gy and 80–100 Gy for thyroid remnant and DTC metastases, respectively [340–344].
The 124I-iodide effective dose per administrated activity is 0.095 mSv/MBq with a thyroid uptake of 0% and increases to1.5 mSv/MBq with a thyroid uptake of 35% [345]. Therefore, the effective dose is equal to 7.0 mSv for an administrated activity of 74 MBq, which is comparable to that of other routine nuclear medicine scans [345].
Caveat:
“Effective Dose” is a protection quantity that provides a dose value related to the probability of health detriment to an adult reference person due to stochastic effects from exposure to low doses of ionizing radiation. It should not be used to quantify the radiation risk for a single individual associated with a particular nuclear medicine examination. It is used to characterize a certain examination in comparison to alternatives, but it should be emphasized that if the actual risk to a certain patient population is to be assessed, it is mandatory to apply risk factors (per mSv) that are appropriate for the gender, the age distribution and the disease state of that population."
If serum Tg levels suggest persistence/recurrence of disease after initial treatment (i.e. suppressed Tg > 5 ng/ml) [148]. and the principal diagnostic procedures, such as neck ultrasonography, diagnostic 131I-WBS/123I-WBS and 18F-FDG-PET/CT are unable to identify structural disease amenable to directed therapy (surgical, thermal ablation or external beam radiotherapy), a second empiric RAI can be considered, in order to identify the site of disease and to provide therapeutic benefit. However, this approach fails in over 50% of patients [346]. In this regard, imaging biomarkers able to predict which patents will respond to further RAI therapies are required, in order to spare the patient any further fruitless exposure. This is particularly important in paediatric patients.
The main goals of 124I-PET/CT are to identify iodine-avid DTC localizations with high sensitivity [347,348]. with a low radiation exposure of patients and to perform a personalized dosimetry. Such a clinical technique, coupled with the routine diagnostic practices, on one side could improve patients’ DTC staging or re-staging and on the other side could allow nuclear medicine physicians to select those who will actually benefit from RAI [349].
In clinical applications, the pretherapy 124I-PET dosimetry may result in a significant alteration in the therapeutic procedure compared to standard therapy using fixed therapeutic activities. In this context, 124I-PET dosimetry is a useful procedure especially in advanced DTC, and allows the administration of safer and more effective radioiodine activities as well as earlier multimodal interventions compared to standard empirical protocols [350].