Guiding principles on the education and practice of theranostics.

PURPOSE: The recent development and approval of new diagnostic imaging and therapy approaches in the field of theranostics have revolutionised nuclear medicine practice. To ensure the provision of these new imaging and therapy approaches in a safe and high-quality manner, training of nuclear medicine physicians and qualified specialists is paramount. This is required for trainees who are learning theranostics practice, and for ensuring minimum standards for knowledge and competency in existing practising specialists. METHODS: To address the need for a training curriculum in theranostics that would be utilised at a global level, a Consultancy Meeting was held at the IAEA in May 2023, with participation by experts in radiopharmaceutical therapy and theranostics including representatives of major international organisations relevant to theranostics practice. RESULTS: Through extensive discussions and review of existing curriculum and guidelines, a harmonised training program for theranostics was developed, which aims to ensure safe and high quality theranostics practice in all countries. CONCLUSION: The guiding principles for theranostics training outlined in this paper have immediate relevance for the safe and effective practice of theranostics.

Comparison of MRI, [18F]FDG PET/CT, and 99mTc-UBI 29-41 scintigraphy for postoperative spondylodiscitis-a prospective multicenter study.

PURPOSE: Postoperative infection still constitutes an important complication of spine surgery, and the optimal imaging modality for diagnosing postoperative spine infection has not yet been established. The aim of this prospective multicenter study was to assess the diagnostic performance of three imaging modalities in patients with suspected postoperative spine infection: MRI, [18F]FDG PET/CT, and SPECT/CT with 99mTc-UBI 29-41. METHODS: Patients had to undergo at least 2 out of the 3 imaging modalities investigated. Sixty-three patients enrolled fulfilled such criteria and were included in the final analysis: 15 patients underwent all 3 imaging modalities, while 48 patients underwent at least 2 imaging modalities (MRI + PET/CT, MRI + SPECT/CT, or PET/CT + SPECT/CT). Final diagnosis of postoperative spinal infection was based either on biopsy or on follow-up for at least 6 months. The MRI, PET/CT, and SPECT/CT scans were read blindly by experts at designated core laboratories. Spine surgery included metallic implants in 46/63 patients (73%); postoperative spine infection was diagnosed in 30/63 patients (48%). RESULTS: Significant discriminants between infection and no infection included fever (P = 0.041), discharge at the wound site (P < 0.0001), and elevated CRP (P = 0.042). There was no difference in the frequency of infection between patients who underwent surgery involving spinal implants versus those who did not. The diagnostic performances of MRI and [18F]FDG PET/CT analyzed as independent groups were equivalent, with values of the area under the ROC curve equal to 0.78 (95% CI: 0.64-0.92) and 0.80 (95% CI: 0.64-0.98), respectively. SPECT/CT with 99mTc-UBI 29-41 yielded either unacceptably low sensitivity (44%) or unacceptably low specificity (41%) when adopting more or less stringent interpretation criteria. The best diagnostic performance was observed when combining the results of MRI with those of [18F]FDG PET/CT, with an area under the ROC curve equal to 0.938 (95% CI: 0.80-1.00). CONCLUSION: [18F]FDG PET/CT and MRI both possess equally satisfactory diagnostic performance in patients with suspected postoperative spine infection, the best diagnostic performance being obtained by combining MRI with [18F]FDG PET/CT. The diagnostic performance of SPECT/CT with 99mTc-UBI 29-41 was suboptimal in the postoperative clinical setting explored with the present study.

Advances in radioguided surgery in oncology.

The sentinel lymph node (SLN) biopsy is probably the most well-known radioguided technique in surgical oncology. Today SLN biopsy reduces the morbidity associated with lymphadenectomy and increases the identification rate of occult lymphatic metastases by offering the pathologist the lymph nodes with the highest probability of containing metastatic cells. These advantages may result in a change in clinical management both in melanoma and breast cancer patients. The SLN evaluation by pathology currently implies tumor burden stratification for further prognostic information. The concept of SLN biopsy includes pre-surgical lymphoscintigraphy as a "roadmap" to guide the surgeon toward the SLNs and to localize unpredictable lymphatic drainage patterns. In addition to planar images, SPECT/CT improves SLN detection, especially in sites closer to the injection site, providing anatomic landmarks which are helpful in localizing SLNs in difficult to interpret studies. The use of intraoperative imaging devices allows a better surgical approach and SLN localization. Several studies report the value of such devices for excision of additional sentinel nodes and for monitoring the whole procedure. The combination of preoperative imaging and radioguided localization constitutes the basis for a whole spectrum of basic and advanced nuclear medicine procedures, which recently have been encompassed under the term "guided intraoperative scintigraphic tumor targeting" (GOSTT). Excepting SLN biopsy, GOSTT includes procedures based on the detection of target lesions with visible uptake of tumor-seeking radiotracers on SPECT/CT or PET/CT enabling their subsequent radioguided excisional biopsy for diagnostic of therapeutic purposes. The incorporation of new PET-tracers into nuclear medicine has reinforced this field delineating new strategies for radioguided excision. In cases with insufficient lesion uptake after systemic radiotracer administration, intralesional injection of a tracer without migration may enable subsequent excision of the targeted tissue. This approach has been helpful in non-palpable breast cancer and in solitary pulmonary nodules. The introduction of allied technologies like fluorescence constitutes a recent advance aimed to refine the search for SLNs and tracer-avid lesions in the operation theatre in combination with radioguidance.

Standardization of MRI and Scintigraphic Scores for Assessing the Severity of Bone Marrow Involvement in Adult Patients With Type 1 Gaucher Disease.

OBJECTIVE: MRI and (99m)Tc-sestamibi scintigraphy are used to estimate bone marrow infiltration in patients with Gaucher disease (GD), but comparison of data obtained at different institutions is difficult because different scores are employed for semiquantitative assessment. We developed normalized scores for comparing data both within a single method (MRI) and between different methods (MRI versus scintigraphy). MATERIALS AND METHODS: We evaluated 51 patients with type 1 GD (26 women, 25 men; mean age ± SD, 36.3 ± 10.9 years old). T1- and T2-weighted turbo spin-echo sequences at 1.5 T served to derive the bone marrow burden score (0-16), the vertebra-disk ratio (VDR), the Terk score (0-3), and the Spanish-MRI score (S-MRI, 0-24). Scintigraphy was scored between 0 and 8. Each score was normalized into four categories: 0 = normal, 1 = mild, 2 = intermediate, 3 = severe involvement. Interobserver and intraobserver agreements were evaluated by kappa statistics; nonparametric statistics with Bonferroni correction assessed correlations among the various original and normalized scores. RESULTS: Interobserver agreement was excellent for the original scores (κ = 0.730-0.843) and even more so for the normalized scores (κ = 0.775-0.940). Intraobserver agreement kappa values ranged from 0.753 to 0.937 for the original scores and 0.851 to 1.000 for the normalized scores. Highly significant correlations were found among the various original scores (r = 0.42-0.86, p values between 0.0296 and < 0.0001), except for VDR versus S-MRI and Terk. Normalization generally induced marginal reductions in statistical significance, whereas S-MRI versus VDR reached statistical significance with the normalized scores. CONCLUSION: Our data indicate no significant loss of statistical information is caused by the normalization we employed. Our approach therefore facilitates comparison of different scores obtained in different institutions with different imaging modalities.

Radium 223 dichloride: a multidisciplinary approach to metastatic castration-resistant prostate cancer.

The role of nuclear medicine physicians in the multidisciplinary team for the management of patients with prostate cancer has been restricted because of a lack of available tools. The only drugs approved to relieve pain related to bone metastases were ß-emitting radiopharmaceuticals. These drugs did not prove to prolong survival when used as single agent and resulted associated with important adverse events. This situation has changed with the introduction of radium 223 because of evidence of improved survival in patients, the good safety profile and the opportunity to avoid clonal selection of tumor cells. Cooperation among physicians involved in cancer management will lead to improvements in the treatment of bone metastases due to prostate cancer and is thought to extend to other tumor types.

Mozart, music and medicine.

According to the first publication in 1993 by Rauscher et al. [Nature 1993;365:611], the Mozart effect implies the enhancement of reasoning skills solving spatial problems in normal subjects after listening to Mozart's piano sonata K 448. A further evaluation of this effect has raised the question whether there is a link between music-generated emotions and a higher level of cognitive abilities by mere listening. Positron emission tomography and functional magnetic resonance imaging have revealed that listening to pleasurable music activates cortical and subcortical cerebral areas where emotions are processed. These neurobiological effects of music suggest that auditory stimulation evokes emotions linked to heightened arousal and result in temporarily enhanced performance in many cognitive domains. Music therapy applies this arousal in a clinical setting as it may offer benefits to patients by diverting their attention from unpleasant experiences and future interventions. It has been applied in the context of various important clinical conditions such as cardiovascular disorders, cancer pain, epilepsy, depression and dementia. Furthermore, music may modulate the immune response, among other things, evidenced by increasing the activity of natural killer cells, lymphocytes and interferon-γ, which is an interesting feature as many diseases are related to a misbalanced immune system. Many of these clinical studies, however, suffer from methodological inadequacies. Nevertheless, at present, there is moderate but not altogether convincing evidence that listening to known and liked music helps to decrease the burden of a disease and enhances the immune system by modifying stress.

Weighted registration of 123I-FP-CIT SPECT images improves accuracy of binding potential estimates in pathologically low striatal uptake.

To test whether the use of a striatum weighted image may improve registration accuracy and diagnostic outcome in patients with parkinsonian syndromes (PS), weighted images were generated by increasing signal intensity of striatal voxels and used as intermediate dataset for co-registering the brain image onto template. Experimental validation was performed using an anthropomorphic striatal phantom. (123)I-FP-CIT SPECT binding ratios were manually determined in 67 PS subjects and compared to those obtained using unsupervised standard (UWR) and weighted registered (WR) approach. Normalized cost function was used to evaluate the accuracy of phantom and subjects registered images to the template. Reproducibility between unsupervised and manual ratios was assessed by using intra-class correlation coefficient (ICC) and Bland and Altman analysis. Correlation coefficient was used to assess the dependence of semi-quantitative ratios on clinical findings. Weighted method improves accuracy of brain registration onto template as determined by cost function in phantom (0.86 ± 0.06 vs. 0.98 ± 0.02; Student's t-test, P = 0.04) and in subject scans (0.69 ± 0.06 vs. 0.53 ± 0.06; Student's t-test, P < 0.0001). Agreement between manual and unsupervised derived binding ratios as measured by ICC was significantly higher on WR as compared to UWR images (0.91 vs. 0.76). Motor UPDRS score was significantly correlated with manual and unsupervised derived binding potential. In phantom, as well as in subjects studies, correlations were more significant using the WR method (BPm: R(2) = 0.36, P = 0.0001; BPwr: R(2) = 0.368, P = 0.0001; BPuwr: R(2) = 0.300, P = 0.0008). Weighted registration improves accuracy of binding potential estimates and may be a promising approach to enhance the diagnostic outcome of SPECT imaging, correlation with disease severity, and for monitoring disease progression in Parkinsonian syndromes.

Microalbuminuria predicts silent myocardial ischaemia in type 2 diabetes patients.

PURPOSE: Myocardial ischaemia is frequently silent in patients with type 2 diabetes. Although it has been proposed as a potential screening tool, the role of myocardial perfusion single photon emission computed tomography (MPS) has recently been questioned, due to the low prevalence of positive scans and the low rate of cardiac events. The aim of this study was to assess if pretest clinical variables can identify a subgroup of asymptomatic patients with type 2 diabetes at risk of silent myocardial ischaemia and a subsequent poor outcome METHODS: This prospective study included 77 patients (50 men, mean age 63 ± 9 years) with type 2 diabetes and no known coronary artery disease (CAD) or angina pectoris who underwent gated MPS to screen for CAD between March 2006 and October 2008. MPS images were interpreted using a semiquantitative visual 20-segment model to define summed stress, rest and difference scores. Ischaemia was defined as a sum difference score (SDS) ≥2. Patients were followed-up (median 4.1 years, range 0.8 - 6.1 years) and cardiac hard events (cardiac death or nonfatal myocardial infarction) were recorded. RESULTS: Silent ischaemia was detected in 25 of the 77 patients (32 %). Specifically, 10 patients (13 %) had mild ischaemia (SDS 2 to ≤4) and 15 patients (19 %) had severe ischaemia (SDS >4). In univariate binary logistic analysis, microalbuminuria was the only significant predictor of silent ischaemia on MPS (odds ratio 4.42, 95 % CI 1.27 - 15.40; P = 0.019). The overall accuracy of microalbuminuria for predicting silent ischaemia was 71.4 % and was 89.6 % for predicting severe ischaemia. Kaplan-Meier curves showed no significant group differences in 5-year cardiac event-free survival between patients with and those without microalbuminuria, or between patients with SDS ≥2 and those with SDS <2. In contrast, 5-year event-free survival was significantly lower in patients with SDS >4 than in patients with SDS ≤4: 55.6 % (95 % CI 39.0 - 72.2 %) vs. 94.5 % (95 % CI: 91.4 - 97.6 %), respectively (Breslow test, chi-square 20.9, P < 0.001). Median cardiac event-free survival was not observed in the whole group, while the 25th percentile of cardiac event-free survival was reached only in patients with SDS >4 (2.3 years). In univariate Cox regression analysis, SDS >4 predicted cardiac event-free survival (hazard ratio 12.87, 95 % CI 2.86 - 27.98; P = 0.001), while SDS ≥2 did not (hazard ratio 2.78, 95 % CI 0.62 - 12.46, P = 0.16). CONCLUSION: In this group of patients with type 2 diabetes, microalbuminuria was the only predictor of silent ischaemia on MPS. Assessment of microalbuminuria should be routinely considered among the first risk stratification steps for CAD in patients with type 2 diabetes, even though severe ischaemia on MPS is a major predictor of cardiac event-free survival.

Radio-guided thoracoscopic surgery (RGTS) of small pulmonary nodules.

BACKGROUND: The demand for adequate tissue sampling to determine individual tumor behavior is increasing the number of lung nodule resections, even when the diagnosis is already recognized. Video-assisted thoracic surgery (VATS) is the procedure of choice for diagnosis and treatment of small pulmonary nodules. Difficulties in localizing smaller and deeper nodules have been approached with different techniques. Herein we report our 13-years' experience with radio-guided thoracoscopic resection. METHODS: Patients with pulmonary nodules smaller than 1 cm and/or deeper than 1 cm, below the visceral pleura, underwent computed tomography (CT)-guided injection of a solution, composed of 0.2 ml (99)Tc-labeled human serum albumin microspheres and 0.1 ml nonionic contrast, into the nodule. During the VATS procedure, an 11-mm-diameter collimated probe connected to a gamma ray detector was introduced to scan the lung surface. The area of major radioactivity, which matched with the area of the nodule, was resected. RESULTS: From 1997 to 2009, 573 patients underwent thoracoscopic resection of small pulmonary nodules, 211 with the radio-guided technique. There were 159 men and 52 women, with an average age of 60.6 years (range = 12-83). The mean duration of the surgical procedure was 41 min (range = 20-100). The procedure was successful in 208/211 cases. Three patients (0.5%) required conversion to a minithoracotomy. The mean length of pleural drainage and hospital stay was 2.3 and 3.7 days, respectively. Histological examination showed 98 benign lesions and 113 malignant lesions (61 metastases and 52 primary lung cancers). CONCLUSION: This study confirms that radio-guided localization of small pulmonary nodules is a feasible, safe, and quick procedure, with a high rate of success. The spread of the sentinel lymph node technique has increased the availability of technology required for RGTS.

Sentinel Lymph Node Methods in Breast Cancer.

Breast cancer is the most frequent cancer diagnosed in women worldwide. Accurate lymph node staging is essential for both prognosis (of early-stage disease) and treatment (for regional control of disease) in patients with breast cancer. The sentinel lymph nodes are the regional nodes that directly drain lymph from the primary tumor. No imaging modality is accurate enough to detect lymph node metastases when a primary breast cancer is at an early stage (I or II), but sentinel lymph node biopsy is a highly reliable method for screening axillary nodes and for identifying metastatic (including micro-metastatic) disease in regional lymph nodes. Despite the widespread use of sentinel lymph node biopsy for early-stage breast cancer, relevant variations have been described regarding practical aspects of the procedure, and some variability has initially been reported regarding the rates of intraoperative sentinel lymph node identification and of false-negative findings, most likely because of differences in the size of the populations being investigated and in lymphatic mapping techniques. Nevertheless, using adequate learning curves and once a multidisciplinary team is experienced with the procedure, improved levels of accuracy are achieved.

Expression of the oncofetal ED-B-containing fibronectin isoform in hematologic tumors enables ED-B-targeted 131I-L19SIP radioimmunotherapy in Hodgkin lymphoma patients.

Current treatment of hematologic malignancies involves rather unspecific chemotherapy, frequently resulting in severe adverse events. Thus, modern clinical research focuses on compounds able to discriminate malignant from normal tissues. Being expressed in newly formed blood vessels of solid cancers but not in normal mature tissues, the extradomain B of fibronectin (ED-B FN) is a promising target for selective cancer therapies. Using immunohistology with a new epitope retrieval technique for paraffin-embedded tissues, ED-B FN expression was found in biopsies from more than 200 Hodgkin and non-Hodgkin lymphoma patients of nearly all entities, and in patients with myeloproliferative diseases. ED-B FN expression was nearly absent in normal lymph nodes (n = 10) and bone marrow biopsies (n = 9). The extent of vascular ED-B FN expression in lymphoma tissues was positively correlated with grade of malignancy. ED-B FN expression was enhanced in lymph nodes with severe lymphadenopathy and in some hyperplastic tonsils. The in vivo accessibility of ED-B FN was confirmed in 3 lymphoma patients, in whom the lymphoma lesions were visualized on scintigraphy with (131)I-labeled L19 small immunoprotein ((131)I-L19SIP). In 2 relapsed Hodgkin lymphoma patients(131)I-L19SIP radioimmunotherapy induced a sustained partial response, qualifying ED-B FN as a promising target for antibody-based lymphoma therapies.

Adrenal masses in patients with cancer: PET/CT characterization with combined CT histogram and standardized uptake value PET analysis.

OBJECTIVE: Our purpose was to determine the diagnostic performance of 18F-FDG PET/CT for characterizing adrenal masses in patients with cancer, combining standardized uptake value (SUV) and CT histogram analysis. MATERIALS AND METHODS: A total of 117 adrenal masses in 93 patients with cancer (61 men and 32 women; mean [± SD] age, 67.2 ± 10.3 years; range, 38-84 years) were evaluated with FDG PET/CT. Of the 117 lesions, 42 were malignant according to histopathologic analysis or size change, whereas 75 were benign on the basis of stability for 6 months. Size, mean attenuation value, percentage of negative pixels at CT histogram analysis, maximum SUV (SUV(max)), and average SUV were calculated for each adrenal lesion. Moreover, FDG adrenal uptake was compared with radioactivity of the aorta, liver, and spleen by calculating the SUV ratios of adrenal lesion to aorta, adrenal lesion to liver, and adrenal lesion to spleen. PET/CT value was assessed by using independent t tests and receiving operating characteristic (ROC) analysis. RESULTS: There was a statistically significant difference in size, attenuation value, percentage of negative pixels, and SUV between benign and malignant masses. All malignant lesions showed FDG activity higher than that in liver, spleen, and aorta, with SUV(max) greater than 2.8 in all cases, whereas with the CT histogram analysis, all lesions with a percentage of negative pixels higher than 10% were benign. Combined SUV and CT histogram analysis yielded 100% sensitivity, 97.3% specificity, 95.7% positive predictive value, and 100% negative predictive value. At ROC analysis, combined SUV and CT histogram analysis (area under the ROC curve [AUC], 0.996) was more accurate than simple SUV(max) analysis (AUC, 0.961) and the combination of SUV(max) and attenuation value (AUC, 0.987). CONCLUSION: The combination of SUV and CT histogram analysis allowed us to significantly improve the PET/CT diagnostic accuracy for characterizing adrenal lesions, leading to a significant reduction in the number of false-positive cases.

Implementing sentinel lymph node biopsy programs in developing countries: challenges and opportunities.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is the accepted standard of care in early-stage breast cancer and cutaneous melanoma. This technology is accurate for nodal staging and determining the prognosis of these patients. There are several randomized controlled trials confirming the accuracy of this technique and confirming its role in reducing morbidity and improving quality of life. It is also gaining increased acceptance in the management of other solid tumors. Despite the established benefits of SLNB as a minimally invasive approach for nodal staging, the procedure is still underutilized in many developing countries. METHODS: The Human Health Division of the International Atomic Energy Agency (IAEA) convened advisory meetings with panels of multidisciplinary experts from different backgrounds with the remit to analyze the difficulties encountered by developing countries in establishing a successful SLNB program. The other remit of the panel was to recommend an effective program based on existing evidence that can be adapted and implemented in developing countries. The experience of some members of the panel in the training for this technique in Asia, Latin America, and Africa provided the insight required for the development of a comprehensive and structured program. The panel included recommendations on the technical aspects of the procedure, as well as a comprehensive training program, including theoretical teaching, practical training in surgical skills, laboratories, and hands-on proctored learning. Particular emphasis was placed on in-built quality assurance requirements to ensure that this powerful staging investigation is implemented with the highest possible standard in the management of cancer patients, with the lowest false negative rate. CONCLUSIONS: It is hoped that this article will be a useful resource for our colleagues planning to establish a SLNB program.

Current role of 111In-DTPA-octreotide scintigraphy in diagnosis of thymic masses.

AIMS AND BACKGROUND: Thymic tumors (thymomas and thymic carcinomas) represent 50% of all mediastinal tumors. Thymomas usually express high levels of somatostatin receptors, which enable in vivo imaging with 111In-DTPA-octreotide (OctreoScan®). The aim of this study was to further investigate the role of radionuclide techniques in the diagnosis, staging and follow-up of these tumors. METHODS: Eight patients (5 women, 3 men, age range 35-79 years; mean ± SD 56.1 ± 15.8 years) entered the study. In 4 patients, myasthenia gravis was the presenting symptom. 111In-DTPA-octreotide scan was performed within 3 weeks after contrast enhanced CT and/or MRI. Planar and tomographic images were acquired within 24 hours of the injection of 111 MBq OctreoScan. The scintigraphic results were defined in correlation with the histological findings. RESULTS: Histology revealed thymoma in 3 patients, thymic carcinoma in 1, insular carcinoma of presumably thymic origin in 1, thymic carcinoid in 1, and thymic hyperplasia in 2 patients. Two thymomas were at stage I, 1 thymoma and 1 thymic carcinoma at stage II, 1 insular carcinoma of presumably thymic origin at stage IV, and 1 thymic carcinoid at stage IV. OctreoScan consistently accumulated in primary and/or metastatic sites of thymic tumors while no radiotracer uptake was detected in the 2 patients with benign thymic hyperplasia. In 1 patient with a very large mediastinal mass (13 cm in largest diameter) and multiple metastatic deposits in the lungs, OctreoScan scintigraphy showed a large area of pathological uptake in the anterior mediastinum and a small area of focal uptake in the cervical-dorsal region of the right lung corresponding to a lymph node expressing somatostatin receptors. CONCLUSIONS: OctreoScan is avidly taken up by thymic tumors, enabling the diagnosis of these tumors and a better evaluation of their extension. It does not accumulate in thymic hyperplasia, thus allowing the differential diagnosis between these 2 pathological conditions. In patients affected by myasthenia gravis, OctreoScan scintigraphy can play an important role in characterizing thymic masses.

The Role of Nuclear Medicine in the Clinical Management of Benign Thyroid Disorders, Part 1: Hyperthyroidism.

Benign thyroid disorders, especially hyper- and hypothyroidism, are the most prevalent endocrine disorders. The most common etiologies of hyperthyroidism are autoimmune hyperthyroidism (Graves disease, GD), toxic multinodular goiter (TMNG), and toxic thyroid adenoma (TA). Less common etiologies include destructive thyroiditis (e.g., amiodarone-induced thyroid dysfunction) and factitious hyperthyroidism. GD is caused by autoantibodies against the thyroid-stimulating hormone (TSH) receptor. TMNG and TA are caused by a somatic activating gain-of-function mutation. Typical laboratory findings in patients with hyperthyroidism are low TSH, elevated free-thyroxine and free-triiodothyronine levels, and TSH-receptor autoantibodies in patients with GD. Ultrasound imaging is used to determine the size and vascularity of the thyroid gland and the location, size, number, and characteristics of thyroid nodules. Combined with lab tests, these features constitute the first-line diagnostic approach to distinguishing different forms of hyperthyroidism. Thyroid scintigraphy with either radioiodine or 99mTc-pertechnetate is useful to characterize different forms of hyperthyroidism and provides information for planning radioiodine therapy. There are specific scintigraphic patterns for GD, TMNG, TA, and destructive thyroiditis. Scintigraphy with 99mTc-sestamibi allows differentiation of type 1 from type 2 amiodarone-induced hyperthyroidism. The radioiodine uptake test provides information for planning radioiodine therapy of hyperthyroidism. Hyperthyroidism can be treated with oral antithyroid drugs, surgical thyroidectomy, or 131I-iodide. Radioiodine therapy is generally considered after failure of treatment with antithyroid drugs, or when surgery is contraindicated or refused by the patient. In patients with TA or TMNG, the goal of radioiodine therapy is to achieve euthyroid status. In GD, the goal of radioiodine therapy is to induce hypothyroidism, a status that is readily treatable with oral thyroid hormone replacement therapy. Dosimetric estimates based on the thyroid volume to be treated and on radioiodine uptake should guide selection of the 131I-activity to be administered. Early side effects of radioiodine therapy (typically mild pain in the thyroid) can be handled by nonsteroidal antiinflammatory drugs. Delayed side effects after radioiodine therapy for hyperthyroidism are hypothyroidism and a minimal risk of radiation-induced malignancies.

The Role of Nuclear Medicine in the Clinical Management of Benign Thyroid Disorders, Part 2: Nodular Goiter, Hypothyroidism, and Subacute Thyroiditis.

Part 2 of this series of Continuing Education articles on benign thyroid disorders deals with nodular goiter, hypothyroidism, and subacute thyroiditis. Together with Part 1 (which dealt with various forms of hyperthyroidism), this article is intended to provide relevant information for specialists in nuclear medicine dealing with the clinical management of patients with benign thyroid disorders, the primary audience for this series. Goiter, an enlargement of the thyroid gland, is a common endocrine abnormality. Constitutional factors, genetic abnormalities, or dietary and environmental factors may contribute to the development of nodular goiter. Most patients with nontoxic nodular goiter are asymptomatic or have only mild mechanical symptoms (globus pharyngis). Work-up of these patients includes measurement of thyroid-stimulating hormone, free triiodothyronine, free thyroxine, thyroid autoantibodies, ultrasound imaging, thyroid scintigraphy, and fine-needle aspiration biopsy of nodules with certain ultrasound and scintigraphic features. Treatment for multinodular goiter includes dietary iodine supplementation, surgery, radioiodine therapy (to decrease thyroid size), and minimally invasive ablation techniques. Hypothyroidism ranges from rare cases of myxedema to more common mild forms (subclinical hypothyroidism). Primary hypothyroidism often has an autoimmune etiology. Clinical presentations differ in neonates, children, adults, and elderly patients. Work-up includes thyroid function tests and ultrasound imaging. Nuclear medicine is primarily used to locate ectopic thyroid tissue in congenital hypothyroidism or to detect defects in iodine organification with the perchlorate discharge test. Treatment consists of thyroid replacement therapy with l-thyroxine, adjusting the daily dose to the individual patient's metabolic and hormonal requirements. Subacute thyroiditis is a self-limited inflammatory disorder of the thyroid gland, often associated with painless or painful swelling of the gland and somatic signs or symptoms. Inflammation disrupts thyroid follicles resulting in a rapid release of stored thyroxine and triiodothyronine causing an initial thyrotoxic phase, often followed by transient or permanent hypothyroidism. Although subacute thyroiditis is often related to a viral infection, no infective agent has been identified. Subacute thyroiditis may be caused by a viral infection in genetically predisposed individuals. Work-up includes lab tests, ultrasound imaging, and radionuclide imaging. Thyroid scintigraphy demonstrates different findings depending on the phase of the illness, ranging from very low or absent tracer uptake in the thyroid gland in the hyperthyroid phase to a normal appearance in the late recovery phase. Since subacute thyroiditis is self-limited, treatment is directed toward relief of pain. High-dose nonsteroidal antiinflammatory drugs are usually the first-line treatment. If severe pain persists, a course of corticosteroids may be necessary. Permanent hypothyroidism develops in up to 15% of patients with subacute thyroiditis, even more than 1 y after presentation.

A review on the clinical uses of SPECT/CT.

In the era when positron emission tomography (PET) seems to constitute the most advanced application of nuclear medicine imaging, still the conventional procedure of single photon emission computed tomography (SPECT) is far from being obsolete, especially if combined with computed tomography (CT). In fact, this dual modality imaging technique (SPECT/CT) lends itself to a wide variety of useful diagnostic applications whose clinical impact is in most instances already well established, while the evidence is growing for newer applications. The increasing availability of new hybrid SPECT/CT devices with advanced technology offers the opportunity to shorten acquisition time and to provide accurate attenuation correction and fusion imaging. In this review we analyse and discuss the capabilities of SPECT/CT for improving sensitivity and specificity in the imaging of both oncological and non-oncological diseases. The main advantages of SPECT/CT are represented by better attenuation correction, increased specificity, and accurate depiction of the localization of disease and of possible involvement of adjacent tissues. Endocrine and neuroendocrine tumours are accurately localized and characterized by SPECT/CT, as also are solitary pulmonary nodules and lung cancers, brain tumours, lymphoma, prostate cancer, malignant and benign bone lesions, and infection. Furthermore, hybrid SPECT/CT imaging is especially suited to support the increasing applications of minimally invasive surgery, as well as to precisely define the diagnostic and prognostic profile of cardiovascular patients. Finally, the applications of SPECT/CT to other clinical disorders or malignant tumours is currently under extensive investigation, with encouraging results in terms of diagnostic accuracy.

Recombinant human TSH and ablation of post-surgical thyroid remnants in differentiated thyroid cancer: the effect of pre-treatment with furosemide and furosemide plus lithium.

BACKGROUND AND AIM: Recombinant human TSH (rhTSH) can be used for post-surgical radioiodine (I-131) thyroid remnants ablation in differentiated thyroid cancer (DTC) patients after surgery. Debate exists in literature about the optimal amount of I-131 that should be given for obtaining an effective ablation and about the role of iodine pool during treatment. Therefore, the aim of the present study was to assess whether I-131 ablation during rhTSH stimulus can be improved by reducing the circulating iodine pool and by increasing thyroid cell uptake and retention of I-131 obtained by administering furosemide and lithium. METHODS: A total of 201 consecutive DTC patients were entered in the study: they were treated by total thyroidectomy and I-131 therapy during rhTSH stimulus to ablate thyroid remnants. Patients were divided into two groups according to the TNM stage: group 1 included patients in stage I-II who were treated with a low 30-mCi I-131 dose, while group 2 included patients in stage III-IV who were treated by a high 100-mCi I-131 dose. Moreover, both groups were further subdivided into three subgroups. Subgroup (a) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-thyroxine (LT4). Subgroup (b) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-T4, and after furosemide administration (25 mg/day orally) during the 3 days before I-131. Subgroup (c) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day L-T4 withdrawal, and after administration of furosemide (25 mg/day orally) during the 3 days prior I-131 and lithium (450 mg/day orally) during the 3 days following I-131. Another group (group 3) of 20 patients characterized by a very low-risk cancer (unifocal tumor <1.0 cm in diameter, without extra-capsular extension, N0) was treated with a 30-mCi I-131 dose under rhTSH stimulus without performing the short 4-day L-4 withdrawal: this group was taken as the control. Follow-up was performed by neck ultrasonography (US), and Tg measurement and I-131 WBS under rhTSH stimulus. RESULTS: Among the patients from group 1, those pre-treated with furosemide or with furosemide plus lithium showed a better outcome of ablation both in terms of undetectable Tg values (97.7% and 95.5 % vs. 79.5%, p < 0.05) and of WBS negativity (97.7% vs. 81.8%, p < 0.05) during the rhTSH stimulus. No similar findings were observed in group 2 patients. Moreover, in patients from group 3 (I-131 30 mCi, without L-T4 withdrawal), the outcome of ablation was significantly lower in comparison to patients from group 1 (I-131 30 mCi, with L-T4 withdrawal) in terms of undetectable Tg during the rhTSH stimulus (55.0%, p < 0.001). CONCLUSION: rhTSH is highly effective for post-surgical thyroid remnant ablation in low-risk cancer patients using the low 30-mCi dose protocol combined with the short 4-day withdrawal of L-T4. Moreover, in these patients the pre-treatment with furosemide seems to play an important role to further improve the outcome of ablation by reducing the iodine pool.