Radioiodine Imaging Research Articles

Number of Foci of Functioning Thyroid Tissue Remaining after Thyroidectomy for Differentiated Thyroid Cancer: Institutional Experience.

Radioiodine imaging of the neck with a pinhole collimator (PinC) is frequently performed in differentiated thyroid cancer (DTC) patients for visualizing individual, and a total number of foci (NOF) of functioning residual thyroid tissue (FRTT) within the thyroid bed in postthyroidectomy patients. The objective of this study was to determine our experience regarding the NOF of FRTT visualized on pretherapy radioiodine PinC images. We performed a retrospective review of radioiodine PinC images of the neck of patients with very low-risk DTC and who had thyroidectomy performed by selected surgeons at MedStar Washington Hospital Center. For each patient's image, the NOF of FRTT was determined by two blind readers. Statistical analysis was performed. One hundred and twenty-six patients met the criteria. Surgeon (S1, S2, S3, and S4) performed 17, 10, 86, and 13 thyroidectomies, respectively. The analysis (mean, range, and standard deviation) of NOF of FRTT was: S1: (2.2, 0-5, 1.3); S2: (1.6, 1–3, 0.8); S3: (2.6, 0–7, 1.5); S4: (3.3, 1–5, 1.3). The percentages of < 2, ≤3, ≤4, and <5 foci remaining were 4.9%, 21.5%, 77.0%, and 91.3%, respectively. For the selected surgeons, the NOF of FRTT in the thyroid bed or neck in postthyroidectomy patients never exceeded 7, rarely exceeded 5 (2.4%), and infrequently exceeded 4 (8.7%). Based on these data, our thresholds of the NOF for which we perform further workup for possible locoregional disease are ≥5. Each facility is encouraged to establish their own criteria for their facility and preferably for each of their surgeons.

68Ga-DOTATOC PET/CT in Patients with Iodine- and 18F-FDG-Negative Differentiated Thyroid Carcinoma and Elevated Serum Thyroglobulin.

68Ga-DOTATOC PET/CT (CT without contrast, low-dose) was performed on average 6 wk after negative 18F-FDG PET/CT (CT contrast-enhanced, full-dose) in 15 consecutive radioiodine-negative DTC patients with elevated and rising thyroglobulin. Visual assessment of 68Ga-DOTATOC PET/CT images used a 4-point scale for classification of lesions (0, no pathologic findings; 1, benign; 2, equivocal; 3, malignant). PET findings were correlated with the histologic subtype of tumor, levels of serum thyroglobulin, and morphologic findings on full-dose CT and neck ultrasound. Histology or clinical and imaging follow-up served as a reference standard. Analysis was performed on a patient and lesion basis. 68Ga-DOTATOC PET/CT was true-positive in 5 patients (10 tumor lesions) and was false-positive in 1 patient. The rate of positive 68Ga-DOTATOC PET/CT was significantly higher in poorly differentiated/oxyphilic carcinomas (4/4 patients) than in papillary (1/5) or follicular (0/6) tumors. Thyroglobulin levels tended to be higher in patients with tumor localization on 68Ga-DOTATOC PET/CT, but differences were not significant. In 2 of 5 patients with true-positive findings on 68Ga-DOTATOC PET/CT, CT alone but not ultrasound identified 2 of 10 tumor lesions, but in both patients 68Ga-DOTATOC-PET/CT revealed further tumor lesions not detected on CT alone. 68Ga-DOTATOC PET/CT should be considered in the case of negative 18F-FDG PET/CT in radioiodine-negative DTC patients with elevated and rising thyroglobulin. Imaging with 68Ga-DOTATOC appears promising especially in poorly differentiated and oxyphilic subtypes of DTC.

False positive diagnosis on (131)iodine whole-body scintigraphy of differentiated thyroid cancers.

(131)Iodine is used both to ablate any residual thyroid tissue or metastatic disease and to obtain whole-body diagnostic images after total thyroidectomy for differentiated thyroid cancer (DTC). Even though whole-body scan is highly accurate in showing thyroid residues as well as metastases of DTC, false positive results can be found, possibly leading to diagnostic errors and unnecessary treatments. This paper reviews the physiological and pathological processes involved as well as the strategy to recognize and rule out false positive radioiodine images.

Su1910 Adenovirus Expressing Sodium Iodide Symporter (NIS) Targets Pancreatic Cancer for Radioiodine Therapy and Imaging

Su1910 Adenovirus Expressing Sodium Iodide Symporter (NIS) Targets Pancreatic Cancer for Radioiodine Therapy and Imaging

Role of single photon emission computed tomography/computed tomography in diagnostic iodine-131 scintigraphy before initial radioiodine ablation in differentiated thyroid cancer.

Objectives:The study was performed to evaluate the incremental value of single photon emission computed tomography/computed tomography (SPECT/CT) over planar radioiodine imaging before radioiodine ablation in the staging, management and stratification of risk of recurrence (ROR) in differentiated thyroid cancer (DTC) patients.Materials and Methods:Totally, 83 patients (21 male, 62 female) aged 17–75 (mean 39.9) years with DTC were included consecutively in this prospective study. They underwent postthyroidectomy planar and SPECT/CT scans after oral administration of 37–114 MBq iodine-131 (I-131). The scans were interpreted as positive, negative or suspicious for tracer uptake in the thyroid bed, cervical lymph nodes and sites outside the neck. In each case, the findings on planar images were recorded first, without knowledge of SPECT/CT findings. Operative and pathological findings were used for postsurgical tumor–node–metastasis staging. The tumor staging was reassessed after each of these two scans.Results:Single photon emission computed tomography/computed tomography localized radioiodine uptake in the thyroid bed in 9/83 (10.8%) patients, neck nodes in 24/83 (28.9%) patients and distant metastases in 8/83 (9.6%) patients in addition to the planar study. Staging was changed in 8/83 (9.6%), ROR in 11/83 (13.2%) and management in 26/83 (31.3%) patients by the pretherapy SPECT/CT in comparison to planar imaging. SPECT/CT had incremental value in 32/83 patients (38.5%) over the planar scan.Conclusion:Single photon emission computed tomography/computed tomography is feasible during a diagnostic I-131 scan with a low amount of radiotracer. It improved the interpretation of pretherapy I-131 scintigraphy and changed the staging and subsequent patient management.

Cardiac blood pool activity on postablation radioiodine imaging.

There are reports on physiologic and pathologic mediastinal uptake on radioiodine imaging in patients with thyroid carcinoma. The most commonly reported physiologic causes of mediastinal uptake are esophageal retention of salivary secretion and uptake by hyperplastic or normal thymus gland. In this study, we evaluated physiologic cardiac blood pool (CBP) activity and its associated findings on radioiodine imaging. Cardiac blood pool activity was evaluated in 186 postablation and 32 posttherapy scans. After oral radioiodine administration, imaging was initiated on day 7. Thyroglobulin, anti-thyroglobulin and TSH blood level determination was carried out in all patients. Whole-body scans were inspected with regard to residual thyroid uptake, esophageal uptake, CBP activity, hepatic activity and metastatic iodine uptake. Uptake in the residual thyroid tissue was graded visually as mild (m), moderate (M) and significant (S). Whenever CBP activity was detected on visual inspection, its intensity was graded as mild (1), moderate (2), and significant (3). Cardiac blood pool activity was detected in 61 postablation scans (33 %). Residual thyroid uptake was observed in all patients with CBP. A significant correlation existed between the intensity of uptake and the presence of CBP (p < 0.05). The mean Tg in patients with CBP was significantly higher than those without CBP (p < 0.05). Cardiac blood pool activity was not observed in any posttherapy scans and in those scans with distant metastases in the postablation group. Linear or irregular activity pattern thought to be due to esophagus was detected in 4 % of postablation scans. The results have revealed CBP to be common on postablation scans. Its presence correlated with the intensity of residual thyroid uptake and had a significant association with increased thyroglobulin levels. Its absence on posttherapy scans despite increased Tg levels suggested that this activity is due to labeled thyroid hormones released by the residual thyroid tissue. Its presence might imply a high level of blood radiation dose.

Remission of Disseminated Cancer After Systemic Oncolytic Virotherapy

MV-NIS is an engineered measles virus that is selectively destructive to myeloma plasma cells and can be monitored by noninvasive radioiodine imaging of NIS gene expression. Two measles-seronegative patients with relapsing drug-refractory myeloma and multiple glucose-avid plasmacytomas were treated by intravenous infusion of 1011 TCID50 (50% tissue culture infectious dose) infectious units of MV-NIS. Both patients responded to therapy with M protein reduction and resolution of bone marrow plasmacytosis. Further, one patient experienced durable complete remission at all disease sites. Tumor targeting was clearly documented by NIS-mediated radioiodine uptake in virus-infected plasmacytomas. Toxicities resolved within the first week after therapy. Oncolytic viruses offer a promising new modality for the targeted infection and destruction of disseminated cancer.

Molecular imaging agents for SPECT (and SPECT/CT)

The development of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) cameras has increased the diagnostic value of many existing single photon radiopharmaceuticals. Precise anatomical localization of lesions greatly increases diagnostic confidence in bone imaging of the extremities, infection imaging, sentinel lymph node localization, and imaging in other areas. Accurate anatomical localization is particularly important prior to surgery, especially involving the parathyroid glands and sentinel lymph node procedures. SPECT/CT plays a role in characterization of lesions, particularly in bone scintigraphy and radioiodine imaging of metastatic thyroid cancer. In the development of novel tracers, SPECT/CT is particularly important in monitoring response to therapies that do not result in an early change in lesion size. Preclinical SPECT/CT devices, which actually have spatial resolution superior to PET/CT devices, have become essential in characterization of the biodistribution and tissue kinetics of novel tracers, allowing coregistration of serial studies within the same animals, which serves both to reduce biological variability and reduce the number of animals required. In conclusion, SPECT/CT increases the utility of existing radiopharmaceuticals and plays a pivotal role in the evaluation of novel tracers.

SPECT/CT localization of oral radioiodine activity

PurposeWe sought to further localize radioiodine activity in the mouth on post-thyroid cancer therapy imaging using single-photon emission computed tomography/computed tomography (SPECT/CT).Materials and methodsWe retrospectively reviewed all patients (58) who underwent thyroid cancer therapy with iodine-131 (131I) at our institution from August 2009 to March 2011 whose post-therapy radioiodine imaging included neck SPECT/CT. A small group (six) of diagnostic 123I scans including SPECT/CT was also reviewed. Separately, we performed in-vitro 131I (sodium iodide) binding assays with amalgam and Argenco HP 77 (77% dental gold alloy) as proof of principle for these interactions.ResultsOf the 58 post-therapy patients, 45 (78%) had undergone metallic dental restorations, and of them 41 (91%) demonstrated oral 131I activity localizing preferentially to those restorations. It was observed that radioiodine also localized to other dental restorations and to orthodontic hardware. Gum-line activity in edentulous patients suggests radioiodine interaction with denture adhesive.In vitro, dental amalgam and Argenco HP 77 bound 131I in a time-dependent manner over 1–16 days of exposure. Despite subsequent washings with normal saline, significant 131I activity (maximally 12% for amalgam and 68% for Argenco HP 77) was retained by these metals. Subsequent soaking in a saturated solution of potassium iodide partially displaced 131I from amalgam, with near-total displacement of 131I from Argenco HP 77.ConclusionSPECT/CT shows that radioiodine in the oral cavity localizes to metallic dental restorations. Furthermore, in-vitro studies demonstrate partially reversible binding of 131I to common dental metals.

The Changing Role of Oncologists in the Care of Thyroid Cancer Patients

The Changing Role of Oncologists in the Care of Thyroid Cancer Patients

“Hidden” bone metastasis from thyroid carcinoma: A clinical note

The (131)I-iodide ((131)I) whole-body scan, for thyroid carcinoma is at times difficult to interpret. In a diagnostic whole body (131)I scan of a patient with follicular carcinoma, a posterior skull lesion was partially hidden by overlapping facial structures. On lateral head view, the abnormality was clearly evident. SPECT/CT and MRI showed the lesion originated in the occipital bone and had enlarged into the posterior fossa. The mass was surgically removed and the patient received (131)I therapy for residual tissue. The study demonstrates a pitfall in the reading of two dimensional radioiodine images which can be overcome by SPECT or lateral imaging.

SPECT/CT Evaluation of Unusual Physiologic Radioiodine Biodistributions: Pearls and Pitfalls in Image Interpretation

Radioiodine imaging has a well-established role in depicting metastatic disease after thyroidectomy in patients with well-differentiated thyroid cancer. Uptake of radioiodine in thyroid metastases depends on expression of sodium-iodide symporter (NIS) by tumor tissues. However, because radioiodine may also accumulate in normal structures and tissues, it is important to distinguish physiologic radioiodine activity from metastatic disease. Furthermore, secretions that contain radioiodine may also simulate pathologic uptake. A spectrum of physiologic distributions, normal variants, and benign mimics of disease have been described in the literature; yet, even when armed with a comprehensive knowledge of these patterns, interpreting radiologists and nuclear physicians may still encounter diagnostic uncertainty. Single-photon emission computed tomography (SPECT) with integrated computed tomography (CT) is a novel technology that, when applied to diagnostic iodine 123 or iodine 131 ((131)I) radioiodine scintigraphy, may accurately localize and help distinguish benign mimics of disease, with the potential to alter the management plan. SPECT/CT is increasingly being used with radioiodine scintigraphy to evaluate patients with thyroid cancer and shows promise for improving imaging specificity and reducing false-positive results.

Radioiodine scintigraphy with SPECT/CT: an important diagnostic tool for thyroid cancer staging and risk stratification.

Staging and risk stratification predicate the postoperative management of thyroid cancer patients, determining not only the need for (131)I therapy or alternative options (conservative management without ablation, surgical reintervention, or external-beam radiation therapy) but also the long-term follow-up strategy. This paper presents the progress made in the field of thyroid cancer imaging by application of SPECT/CT technology to radioiodine scintigraphy in both diagnostic and post-therapy settings and reviews the impact of fusion radioiodine imaging on staging, risk stratification, and clinical management of patients with thyroid cancer. In addition, this paper addresses the role of preablation radioiodine imaging and provides nuclear medicine physicians with the background knowledge required for integrating information from fusion imaging into the clinical and histopathologic risk stratification for developing an individualized treatment plan for patients with thyroid cancer.

The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS)

New drugs with anti-tumor activity, also able to modify the expression of selected molecules, are under evaluation in breast cancer which is becoming resistant to conventional treatment, or in metastatic disease. The sodium-iodide symporter (NIS), which mediates iodide uptake into thyroid cells, and is the molecular basis of radioiodine imaging and therapy in thyroid cancer, is also expressed in a large portion of breast tumors. Since NIS expression in breast cancer is not sufficient for a significant iodide uptake, drugs able to induce its expression and correct function are under evaluation. In the present study, we report for the first time that the pan-deacetylase (DAC) inhibitor LBH589 (panobinostat) significantly induced NIS, both as mRNA and as protein, through the increase of NIS promoter activity, with the final consequence of obtaining a significant up-take of iodide in MCF7, T47D, and MDA-MB231 breast cancer cells. Moreover, we observed that LBH589 causes a significant reduction in cell viability of estrogen-sensitive and -insensitive breast cancer cells within nanomolar range. The anti-tumor effect of LBH589 is sustained by apoptosis induction and cell cycle arrest in G(2)/M. In conclusion, our data suggest that LBH589 might be a powerful tool in the management of breast cancer due to its multiple effects and support a potential application of LBH589 in the diagnosis and treatment of this disease.

Molecular imaging in thyroid cancer

Molecular imaging plays an important role in the evaluation and management of thyroid cancer. The routine use of thyroid scanning in all thyroid nodules is no longer recommended by many authorities. In the initial work-up of a thyroid nodule, radioiodine imaging can be particularly helpful when the thyroid stimulating hormone level is low and an autonomously functioning nodule is suspected. Radioiodine imaging can also be helpful in the 10–15% of cases for which fine-needle aspiration biopsy is indeterminate. Therapy of confirmed thyroid cancer frequently involves administration of iodine-131 after surgery to ablate remnant tissue. In the follow-up of thyroid cancer patients, increased thyroglobulin levels will often prompt the empiric administration of 131I followed by whole body radioiodine imaging in the search for recurrent or metastatic disease. 131I imaging of the whole body and blood pharmacokinetics can be used to determine if higher doses of 131I can be given in thyroid cancer. The utility of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is steadily increasing. FDG is primarily taken up by dedifferentiated thyroid cancer cells, which are poorly iodine avid. Thus, it is particularly helpful in the patient with an increased thyroglobulin but negative radioiodine scan. FDG PET is also useful in the patient with a neck mass but unknown primary, in patients with aggressive (dedifferentiated) thyroid cancer, and in patients with differentiated cancer where histologic transformation to dedifferentiation is suspected. In rarer types of thyroid cancer, such as medullary thyroid cancer, FDG and other tracers such as 99mTc sestamibi, [11C]methionine, [111In]octreotide, and [68Ga]somatostatin receptor binding reagents have been utilized. 124I is not widely available, but has been used for PET imaging of thyroid cancer and will likely see broader applicability due to the advantages of PET methodology.

Construction of an MUC-1 promoter driven, conditionally replicating adenovirus that expresses the sodium iodide symporter for gene therapy of breast cancer

IntroductionThe sodium iodide symporter (NIS) directs the uptake and concentration of iodide in thyroid cells. This in turn allows radioiodine imaging and therapy for thyroid cancer. To extend the use of NIS-mediated radioiodine therapy to other types of cancer, we successfully transferred and expressed the sodium-iodide symporter (NIS) gene in prostate, colon, and breast cancer cells both in vivo and in vitro by using non-replicating adenoviral vectors.MethodsTo improve virotherapy efficiency, we developed a conditionally replicating adenovirus (CRAd) in which the transcriptional cassette RSV promoter-human NIScDNA-bGH polyA was also inserted at the E3 region. The E1a gene is driven by the tumor-specific promoter MUC-1 in the CRAd Ad5AMUCH_RSV-NIS.ResultsIn vitro infection of the MUC-1-positive breast cell line T47D resulted in virus replication, cytolysis, and release of infective viral particles. Conversely, the MUC-1-negative breast cancer cell line MDA-MB-231 was refractory to the viral cytopathic effect and did not support viral replication. The data indicate that Ad5AMUCH_RSV-NIS activity is stringently restricted to MUC-1-positive cancer cells. Radioiodine uptake was readily measurable in T47 cells infected with Ad5AMUCH_RSV-NIS 24 hours after infection, thus confirming NIS expression before viral-induced cell death.ConclusionsThis construct may allow multimodal therapy, combining virotherapy with radioiodine therapy to be developed as a novel treatment for breast and other MUC1-overexpressing cancers.

Recombinant human thyroid stimulating hormone in 2008: focus on thyroid cancer management

Radioiodine (RAI) ablation following thyroidectomy is standard of care treatment for patients with intermediate or high risk differentiated thyroid cancer. Traditionally, this has been achieved by forgoing thyroid hormone replacement postoperatively, allowing endogenous thyroid stimulating hormone (TSH) levels to rise. This rise in TSH provides the stimulus for RAI uptake by the thyroid remnant, but is associated with clinical hypothyroidism and its associated morbidities. Recombinant human TSH (rhTSH, thyrotropin alfa [Thyrogen(®)], Genzyme Corporation, Cambridge, MA, USA) was developed to provide TSH stimulation without withdrawal of thyroid hormone and clinical hypothyroidism. Phase III studies reported equivalent detection of recurrent or residual disease when rhTSH was used compared with thyroid hormone withdrawal (THW). These trials led to its approval as an adjunctive diagnostic tool for serum thyroglobulin (Tg) testing with or without RAI imaging in the surveillance of patients with differentiated thyroid cancer. Recently, rhTSH was given an indication for adjunctive preparation for thyroid remnant ablation after phase III studies demonstrated comparable outcomes for rhTSH preparation when compared with THW. Importantly, rhTSH stimulation has been found to be safe, well tolerated, and to result in improved quality of life. Here, we review the efficacy and tolerability studies leading to the approval for the use of rhTSH in well-differentiated thyroid cancer management.

Expanding Indications for Recombinant Human TSH in Thyroid Cancer

On December 17, 2007, Genzyme Corporation (Cambridge, MA) announced that the U.S. Food and Drug Administration (FDA) had approved a supplemental indication for Thyrogen®, its brand of recombinant human thyroid-stimulating hormone (rhTSH), to be used in combination with radioiodine to ablate, or destroy, the remaining thyroid tissue in patients who have had surgery for differentiated thyroid cancer. Although rhTSH was first approved for clinical use in the United States, most European and certain Asian and South American countries approved rhTSH for ablation of postsurgical thyroid remnants before the FDA action. In this article we review the timelines for rhTSH approval and present the views of experts from around the world regarding the expanding indications for rhTSH in thyroid cancer.* The commentary concludes with an editorial summary. Timelines for rhTSH Approval† On November 30, 1998, the FDA issued its first approval of rhTSH, as “an adjunctive diagnostic tool for serum thyroglobulin (Tg) testing with or without radioiodine imaging in the follow-up of patients with thyroid cancer” (1). In the original approval, provisions were made for thyroid cancer patients who were unable to mount an endogenous TSH response to hypothyroidism, such as those with pituitary failure. On September 3, 2000, rhTSH was approved in European Union countries‡ for preparation of Tg testing with or without radioiodine imaging for detection of thyroid remnants and well-differentiated thyroid cancer in adult postthyroidectomy patients maintained on hormone suppression therapy. Low-risk patients with well-differentiated thyroid carcinoma who have undetectable serum Tg levels on thyroid hormone suppression could be followed by assaying rhTSH-stimulated serum Tg levels. These indications were adopted in a similar time period by Liechtenstein, Norway, and Iceland, and similar indications were approved by Ukraine on May 17, 2004. On February 23, 2005, rhTSH was approved in Europe for pretherapeutic stimulation and low-risk postthyroidectomy adult patients maintained on hormone suppression therapy for the ablation of thyroid remnant tissue in combination with 3.7 GBq (100 mCi) radioactive iodine (RAI). In Australia (2006), Malaysia (2007), Thailand (2007), and Singapore (2007), government agencies approved indications for rhTSH similar to that adapted by the FDA in 2007. As noted by Dr. Yamashita, rhTSH has not been approved for clinical use in Japan. Prior to the approval of rhTSH for remnant ablation in 2007, the FDA approved label changes on March 11, 2004, and January 1, 1006. These dealt with Thyrogen® Tg testing alone and in combination with radioiodine imaging in patients with metastatic disease and a Quality of Life statement, respectively. In 2006 rhTSH was approved for clinical use by many countries in South America (see below).

Utility of fluorodeoxyglucose-PET in patients with differentiated thyroid carcinoma

In differentiated thyroid carcinoma, persistent plasma thyroglobulin (Tg) is a specific marker for persistent or recurrent disease after thyroidectomy and radioiodine ablation. When Tg remains elevated and no substrate can be found on whole-body radioiodine imaging (131I-WBS), or even when recurrent disease is suspected with normal Tg, conventional imaging (CI) is often insufficient. As fluorodeoxyglucose (FDG)-PET has proven to be an effective modality for detecting various types of cancer, the utility of FDG-PET was analysed and compared with CI in this retrospective study in patients with differentiated thyroid cancer. After total thyroidectomy and radioiodine ablation, 68 FDG-PET scans were performed in 39 patients with elevated Tg levels or clinical suspicion of recurrent disease. At the time of FDG-PET, 54 131I-WBS (in 30 patients) were negative, 14 (in 11 patients) were equivocal. Tg was normal at the time of 14 scans (10 patients) and elevated in 54 (in 33 patients). FDG-PET results were compared with histology, 131I-WBS and CI and clinical follow-up. Sensitivity and specificity were evaluated in various subgroups. Overall, there were 35 true-positive, two false-positive, 20 true-negative and three false-negative FDG-PET scans. In six of these cases (one true positive, five true negative) FDG-PET was repeated without intervention and in an additional eight FDG-PET scans no definite conformation of abnormal FDG-PET could be obtained, so these results were not used for statistical analysis. Sensitivity, specificity, PPV and NPV for the whole group were 92, 88, 94 and 83%, respectively. In 38 scans performed on 31 patients with elevated Tg levels, who were not known with recurrence, this was 84, 100, 100 and 75%, respectively. In 16 scans in 10 patients with known recurrence (all with elevated Tg), sensitivity and PPV were 100% without false-positive or false-negative results. When Tg was not detectable (14 scans in 10 patients), sensitivity, specificity, PPV and NPV were 100, 75, 60 and 100%, respectively. After 35 FDG-PET scans (51%), there was a change in patient management by avoiding ineffective 131I treatment, by guiding surgical reintervention, or avoiding futile surgery. One FP FDG-PET resulted in an unnecessary surgical procedure. In 33 cases, FDG-PET did not lead to a change in treatment policy, which retrospectively would have been beneficial in six cases. FDG-PET affected patient management in patients with differentiated thyroid cancer and negative 131I-WBS, not only when Tg is elevated, but also when Tg is not detectable and therefore the use of FDG-PET as a diagnostic tool is justified in these patients.

Do cell surface trafficking impairments account for variable cell surface sodium iodide symporter levels in breast cancer?

The Na(+)/I(-) symporter (NIS) is a transmembrane glycoprotein that mediates iodide uptake into thyroid follicular cells and serves as the molecular basis of radioiodine imaging and therapy for thyroid cancer patients. The finding that NIS protein is present in 80-90% of breast tumors suggests that breast cancer patients may also benefit from NIS-mediated radionuclide imaging and targeted therapy. However, only 17-25% of NIS-positive breast tumors have detectable radionuclide uptake activity. The discrepancy between NIS expression and radionuclide uptake activity is most likely contributed by variable cell surface NIS protein levels. Apart from the prevalent view that NIS cell surface trafficking impairments account for the variability, our current study proposes that differential levels of NIS expression may also account for variable cell surface NIS levels among breast tumors. We address the need to confirm the identity of intracellular NIS staining to reveal the mechanisms underlying variable cell surface NIS levels. In addition, we warrant a quantitative correlation between cell surface NIS levels and radionuclide uptake activity in patients such that the cell surface NIS levels required for radionuclide imaging can be defined and the defects impairing NIS activity can be recognized.