Joint EANM, SNMMI and IAEA enabling guide: how to set up a theranostics centre.

The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumours and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine. The roll-out of radioligand therapy for treating a high-incidence tumour such as prostate cancer requires the expansion of existing and the establishment of new theranostics centres. Despite wide global variation in the regulatory, financial and medical landscapes, this guide attempts to provide valuable information to enable interested stakeholders to safely initiate and operate theranostics centres. This enabling guide does not intend to answer all possible questions, but rather to serve as an overarching framework for multiple, more detailed future initiatives. It recognizes that there are regional differences in the specifics of regulation of radiation safety, but common elements of best practice valid globally.

Unusual presentations of Carney Complex in patient with a novel PRKAR1A mutation.

Carney Complex (CNC) is a multiple neoplasia syndrome characterized by skin tumors and pigmented lesions, myxomas, and various endocrine tumors. The aim of this case report was to describe a case of CNC with a novel PRKAR1A mutation. A man aged 46 years with a medical history of surgery for cardiac myxomas at the age of 39 was admitted to our hospital because of four newly-developed heart masses. The histologic examination confirmed cardiac myxomas. He had many presentations of CNC such as growth hormone (GH) and prolactin (PRL)-secreting mixed pituitary adenoma, benign thyroid nodule, large-cell calcifying Sertoli cell tumor (LCCST), and superficial angiomyxoma. A bilateral adrenalectomy was performed because the laboratory findings suggested primary pigmented nodular adrenocortical disease (PPNAD). The pathologic examination revealed a focal unilateral PPNAD, unilateral nonpigmented adrenocortical nodule, and bilateral adrenal medullary hyperplasia. Two years after the second cardiac operation, an interatrial septum-derived tumor was detected. An atrial myxoma was confirmed with histologic studies. Based on these findings, the patient was confirmed to have CNC. A novel insertion mutation in the type 1A regulatory subunit of the cAMP-dependent protein kinase A gene (PRKAR1A) in exon 2 was detected in our patient through genetic analysis. The presence of multiple myxomas and endocrine abnormalities should be an indication to physicians to further investigate for CNC. Herein, we described a case of CNC with a novel mutation in exon 2 of the PRKAR1A gene with typical and atypical clinical features.

Nuclear Medicine in Pediatric and Adolescent Tumors.

Nuclear medicine has an important role in the management of many cancers in pediatric age group with multiple imaging modalities and radiopharmaceuticals targeting various biological uptake mechanisms. 18-Flourodeoxyglucose is the radiotracer of choice especially in patients with sarcoma and lymphoma. (18)FDG-PET, for sarcoma and lymphomas, is proved to be superior to conventional imaging in staging and therapy response. Although studies are limited in pediatric population, (18)FDG-PET/CT has found its way through international guidelines. Limitations and strengths of PET imaging must be noticed before adapting PET imaging in clinical protocols. Established new response criteria using multiple parameters derived from (18)FDG-PET would increase the accuracy and repeatability of response evaluation. Current data suggest that I-123 metaiodobenzylguanidine (MIBG) remains the tracer of choice in the evaluation of neuroblastoma (NB) because of its high sensitivity, specificity, diagnostic accuracy, and prognostic value. It is valuable in determining the response to therapy, surveillance for disease recurrence, and in selecting patients for I-131 therapy. SPECT/CT improves the diagnostic accuracy and the interpretation confidence of MIBG scans. (18)FDG-PET/CT is an important complementary to MIBG imaging despite its lack of specificity to NB. It is valuable in cases of negative or inconclusive MIBG scans and when MIBG findings underestimate the disease status as determined from clinical and radiological findings. F-18 DOPA is promising tracer that reflects catecholamine metabolism and is both sensitive and specific. F-18 DOPA scintigraphy provides the advantages of PET/CT imaging with early and short imaging times, high spatial resolution, inherent morphologic correlation with CT, and quantitation. Regulatory and production issues currently limit the tracer's availability. PET/CT with Ga-68 DOTA appears to be useful in NB imaging and may have a unique role in selecting patients for peptide receptor radionuclide therapy with somatostatin analogues. C-11 hydroxyephedrine PET/CT is a specific PET tracer for NB, but the C-11 label that requires an on-site cyclotron production and the high physiologic uptake in the liver and kidneys limit its use. I-124 MIBG is useful for I-131 MIBG pretherapeutic dosimetry planning. Its use for diagnostic imaging as well as the use of F-18 labeled MIBG analogues is currently experimental. PET/MR imaging is emerging and is likely to become an important tool in the evaluation. It provides metabolic and superior morphological data in one imaging session, expediting the diagnosis and lowering the radiation exposure. Radioactive iodines not only detect residual tissue and metastatic disease but also are used in the treatment of differentiated thyroid cancer. However, these are not well documented in pediatric age group like adult patients. Use of radioactivity in pediatric population is very important and strictly controlled because of the possibility of secondary malignities; therefore, management of oncological cases requires detailed literature knowledge. This article aims to review the literature on the use of radionuclide imaging and therapy in pediatric population with thyroid cancer, sarcomas, lymphoma, and NB.

Nuclear Medicine in Thyroid Diseases in Pediatric and Adolescent Patients.

Both benign and malignant diseases of the thyroid are rare in the pediatric and adolescent population, except congenital hypothyroidism. Nuclear medicine plays a major role, both in the diagnosis and therapy of thyroid pathologies. Use of radioactivity in pediatric population is strictly controlled due to possible side effects such as secondary cancers; therefore, management of pediatric patients requires detailed literature knowledge. This article aims to overview current algorithms in the management of thyroid diseases and use of radionuclide therapy in pediatric and adolescent population.

The relationship between changes in functional cardiac parameters following anthracycline therapy and carbonyl reductase 3 and glutathione S transferase Pi polymorphisms.

The aim of this prospective clinical study is to evaluate the relationship between changes in functional cardiac parameters following anthracycline therapy and carbonyl reductase 3 (CBR3p.V244M) and glutathione S transferase Pi (GSTP1p.I105V) polymorphisms. Seventy patients with normal cardiac function and no history of cardiac disease scheduled to undergo anthracycline chemotherapy were included in the study. The patients' cardiac function was evaluated by gated blood pool scintigraphy and echocardiography before and after chemotherapy, as well as 1 year following therapy. Gene polymorphisms were genotyped in 70 patients using TaqMan probes, validated by DNA sequencing. A deteriorating trend was observed in both systolic and diastolic parameters from GG to AA in CBR3p.V244M polymorphism. Patients with G-allele carriers of GSTP1p.I105V polymorphism were common (60%), with significantly decreased PFR compared to patiens with AA genotype. Variants of CBR3 and GSTP1 enzymes may be associated with changes in short-term functional cardiac parameters.

Correlations between histopathologic and scintigraphic parameters of salivary glands in patients with Sjögren's syndrome.

The aim of this study is to evaluate the diagnostic value of quantifying salivary gland scintigraphy in correlation to the labial biopsy findings of Sjögren's syndrome (SS). Thirty patients suspected of having SS referred to our clinic for salivary gland scintigraphy were included to this study. All patients underwent salivary gland biopsy as well. The severity of histopathologic changes was graded according to the Chisholm and Mason scoring system. Dynamic scintigraphy was performed and region of interests (ROI) were drawn. Time activity curves for salivary glands were generated. Count rates of maximum, minimum activity after lemon juice stimuli, and last minute activities of parotid and submandibular glands were obtained. On the basis of this ROI counts, excretion fraction (EF%) was calculated for all salivary glands. The mean EF% for normal parotid gland and pathologic parotid gland was 54.5 ± 13.9 and 45.8 ± 18.42, respectively, while it was 46.7 ± 11.7 for the normal submandibular gland and 29.3 ± 18.8 for the pathologic submandibular gland. With progression in histopathologic grades from 0 to 4, the EF decreased in all salivary glands. Decreased EF in the salivary glands is correlated with the SS, and salivary gland scintigraphy is a sensitive and valid method for evaluation of the function of the salivary glands.

Gastroesophageal reflux scintigraphy: interpretation methods and inter-reader agreement.

BACKGROUND: Scintigraphic imaging is a useful screening tool for patients with suspected gastroesophageal reflux. New scintigraphic interpretation methods have recently been introduced. This study was undertaken to evaluate the efficiency of various scintigraphic interpretation methods in the detection of gastroesophageal reflux and to measure their influence on inter-reader agreement. METHODS: Scintigraphic images of 49 children with suspected gastroesophageal reflux were interpreted by three different methods: visual interpretation, time activity curves, and condensed images. The readings were performed by three specialists and a resident. The discordant results were resolved by a consensus reading done together by all interpreters based on the three different methods. The gastroesophageal refluxes were grouped according to their number, location and intensity. RESULTS: Gastroesophageal reflux scintigraphy revealed 22 patients with negative results and 27 with positive results. The sensitivity, positive predictive value and specificity for each of the three specialists vs. the resident were 96%, 96% and 81% vs. 96%; 93%, 90% and 96% vs. 81%; and 90%, 86%, and 95% vs. 73%, respectively. The mean inter-observer reproducibility (κ value) was 0.910 for visual interpretation, 0.652 for time activity curves and 0.789 for condensed images. Twenty-seven percent of the results were discordant and most of these refluxes were of low grade (92%), low intensity (77%) and localization in the distal esophagus (54%). CONCLUSION: Gastroesophageal scintigraphy is a useful tool for detecting patients with suspected reflux, and visual interpretation is better than the other two methods in terms of accuracy and inter-observer reproducibility.

Is the predicted postoperative FEV1 estimated by planar lung perfusion scintigraphy accurate in patients undergoing pulmonary resection? Comparison of two processing methods.

BACKGROUND: Estimation of postoperative forced expiratory volume in 1 s (FEV1) with radionuclide lung scintigraphy is frequently used to define functional operability in patients undergoing lung resection. We conducted a study to outline the reliability of planar quantitative lung perfusion scintigraphy (QLPS) with two different processing methods to estimate the postoperative lung function in patients with resectable lung disease. METHODS: Forty-one patients with a mean age of 57 +/- 12 years who underwent either a pneumonectomy (n = 14) or a lobectomy (n = 27) were included in the study. QLPS with Tc-99m macroaggregated albumin was performed. Both three equal zones were generated for each lung [zone method (ZM)] and more precise regions of interest were drawn according to their anatomical shape in the anterior and posterior projections [lobe mapping method (LMM)] for each patient. The predicted postoperative (ppo) FEV1 values were compared with actual FEV1 values measured on postoperative day 1 (pod1 FEV1) and day 7 (pod 7 FEV1). RESULTS: The mean of preoperative FEV1 and ppoFEV1 values was 2.10 +/- 0.57 and 1.57 +/- 0.44 L, respectively. The mean of Pod1FEV1 (1.04 +/- 0.30 L) was lower than ppoFEV1 (p < 0.0001) but increased on day 7 (1.31 +/- 0.32 L) (p < 0.0001); however, it never reached the predicted values. Zone and LMMs estimated mean ppoFEV1 as 1.56 +/- 0.45 and 1.57 +/- 0.44 L, respectively. Both methods overestimated the actual value by 50% (ZM), 51% (LMM) and 19% (ZM), 20% (LMM) for pod 1 and pod 7, respectively. This overestimation was more pronounced in patients with chronic lung disease and hilar tumors. No significant differences were observed between ppoFEV1 values estimated by ZM or by LMM (p > 0.05). CONCLUSIONS: PpoFEV1 values predicted by both the zone and LMMs overestimated the actual measured lung volumes in patients undergoing pulmonary resection in the early postoperative period. LMM is not superior to ZM.

Quality control of instant kit 99mTc-mercapto acetyl triglycine with inter- and intra-operator measurements.

This prospective study was aimed to assess inter- and intra-operator variability during routine quality control (QC) procedure for technetium-99m mercaptoacetyl triglycine ((99m)Tc-MAG3) instant kit formulation. A total of 160 QC analyses with thin layer chromatography (TLC) for 20 separate MAG3 re-constitutions were performed by 2 radiochemists. The percentage of free and hydrolysed (99m)Tc as well as binding efficiency, were calculated according to standard TLC. Each QC analysis was done using silica gel (SG), silica acrylic (SA), Whatman 1 (W1) and Whatman 3 (W3) TLC strips separately at 1h, following labeling MAG3 instant kit with (99m)Tc-pertechnetate. To assess the radiochemical stability of (99m)Tc-MAG3, the same analysis was performed 4h after kit reconstitution. Visual confirmation for QC with scintigraphy was also performed. At both time points, each radio-chemist repeated all the procedure twice for each of the TLC paper types to analyze the intra-operator reliability. Crombach's Test was used for the reliability analysis. High inter-operator correlation ratios (range: 0.821-0.920) per each TLC strip were found where the highest concordance rate was 0.921 for SA. Each TLC strip showed adequate kit reconstitution with acceptable free and hydrolysed (99m)Tc percentages both at 1 and 4 h analyses, along with high binding efficiency values of 94.3 +/- 2.9 and 92.5 +/- 1.9 at 1 and 4 h respectively. Intra-observers reliability showed almost equal high concordance rates (range: 0.888-0.961) for all types of strips. In conclusion, all kinds of ITLC/TLC strips were reliable to assess stability of the radiopharmaceutical at 1 and 4 h while analysis with the SA strip had the highest concordence rate. Inter- and intra-operator QC was also reliable.

Gated myocardial perfusion scintigraphy in children with myocarditis: can it be considered as an indicator of clinical outcome?

PURPOSE: Myocarditis is an inflammation of the heart muscle and represents a challenge for diagnosis and treatment. On account of the lack of sensitivity and specificity of routine cardiac tests, there is a need for accurate diagnostic imaging. The aim of this study is to review the role of gated 99Tc-methoxyisobutylisonitrile myocardial perfusion scintigraphy (G-MPS) in the diagnosis and follow-up of the patients with myocarditis in comparison with gallium scintigraphy. MATERIALS AND METHODS: Thirteen patients with a clinical diagnosis of myocarditis were included in the study. All underwent rest G-MPS and the images were then evaluated by quantitative perfusion single-photon emission computed tomography and quantitative gated single photon emission computed tomography software program. Visual evaluation of perfusion was performed as well as analysis of motion with thickening function [expressed as summed rest score, summed motion score, and summed thickening score (STS)] with calculation of ejection fraction (EF) and lung-to-heart (L/H) ratio. Eight patients underwent 67Ga scintigraphy. Clinical, echocardiography, and cardiac enzymes (creatinine kinase-MB, myoglobulin, troponin T, brain natriuretic peptide) data were gathered from the patients' charts. Clinical outcome was grouped according to prognosis. Spearman's correlation (SC) test was used for comparison analysis. RESULTS: Myocardial perfusion defects were observed in eight patients. Perfusion defects in the left ventricle involve a mean of 7.25% (range: 1-11%), whereas wall motion abnormality on G-MPS was more prominent, which showed to be a better marker for myocardial inflammation and necrosis. The 67Ga scintigraphy findings were normal in all, but two. The G-MPS EF (33+/-21%) was slightly lower than the echocardiography EF (40+/-15%), but with close correlation (SC coefficient: 0.635). Comparison of scintigraphic findings with clinical parameters showed that summed motion score with G-MPS EF and STS with L/H ratios were highly correlated (0.932 and 0.622, respectively). The maximum brain natriuretic peptide and L/H ratio with STS were highly correlated with the patients' outcomes (SC coefficient: -0.621, 0.821, and 0.579, respectively), as well. CONCLUSION: Tc-methoxyisobutylisonitrile G-MPS is therefore helpful in providing additional diagnostic and prognostic information in patients with myocarditis.

Mandibular reconstruction in Goldenhar syndrome using temporalis muscle osteofascial flap.

Goldenhar syndrome is a well-known developmental anomaly of the maxillofacial skeleton and hemifacial soft tissue. Maxillofacial anomalies of that syndrome can be managed by a variety of means such as inlay- or onlay-applied nonvascularized bone grafts, vascularized osteocutaneous/osseous flaps, or distraction osteogenesis. Vascularized full-thickness calvarial bone grafting is an important option for mandibular reconstruction for cases in which, for one reason or another, other techniques are not available, not applicable, or have failed. A mandibular defect of a 6-year-old boy presenting with bilateral preauricular skin tags, right microtia, right mandibular hypoplasia (with missing right condylar head and ascending ramus of the mandible) was reconstructed with right vascularized full-thickness calvarial bone grafting. Preoperative three-dimensional computed tomographic scans were used to acquire the stereolithographic biomodeling of the patient for assessing the amount of bone defect and precise planning of the surgery. Panoramic, anteroposterior, and lateral cephalograms and three-dimensional computed tomographic scans were obtained before and after the surgery and in the follow-up period for the evaluation of amount of relapse in the follow-up period. Clinical follow up and bone scintigraphy were used to assess the viability of transferred vascularized calvarial bone graft in the postoperative period. Plain radiographic evaluation with anteroposterior radiographs showed that mandibular symmetry increased and normooclusive closure of incisive teeth was achieved after surgery and retained in the postoperative period. Radiographs taken 1 year after surgery demonstrated that there was a slight relapse (1 mm) to the right side in the mandible when the results were compared with early postoperative ones. Postoperative three-dimensional computed tomographic evaluation of bony structures 3 months after operation showed that the transferred bone retained its volume. Sequential bone scintigraphies, performed to assess the vascularity of the grafts 1 week, 1 month, and 1 year after the operation, demonstrated the viability of transferred vascularized bone graft. The temporalis muscle osteofascial flap is a reliable method for mandibular reconstruction. It lessens the operative time, lessens surgical team labor, minimizes postoperative morbidity and discomfort, minimizes the hospital stay period, and minimizes financial expenses without renouncing the bone-healing capacity and increases aesthetic outcome by camouflaging the donor site scar in scalp and minimizing the facial scarring.

Inter- and intraobserver variability of (99m)Tc-DMSA renal scintigraphy: impact of oblique views.

UNLABELLED: (99m)Tc-Dimercaptosuccinic acid (DMSA) scintigraphy is a frequently used diagnostic test to assess the presence and severity of cortical damage. The aim of this study is to investigate the variability in the interpretation of (99m)Tc-DMSA scans, evaluate the usefulness of oblique images, and assess their impact on scan interpretation. METHODS: Two experienced nuclear medicine physicians independently interpreted 100 (99m)Tc-DMSA scans (197 kidneys) 4 times. Interpretation was twice based on posterior projection images and twice based on posterior and posterior oblique projection images. For each kidney, the observers had to choose between the following results: normal, abnormal, and indeterminate. The indices of variability used were the percentage of agreement, kappa-statistic, and marginal homogeneity. RESULTS: Intraobserver and interobserver reproducibility (kappa-values) varied between 0.683 and 0.708 and between 0.609 and 0.671, respectively, for posterior images. Disagreement in (99m)Tc-DMSA scan interpretation occurred in 18% of kidneys within observers and in 21% of kidneys between observers when only posterior images were used. Oblique views changed the interpretation in 14% and 11.5% of kidneys for the first and second observers, respectively. The use of oblique views increased the agreement rate within and between observers (kappa-values, 0.725-0.812 and 0.768-0.732, respectively; mean agreement, 86.5 and 87.25, respectively). CONCLUSION: Oblique views were found useful in approximately 13% of kidneys and affected inter- and intraobserver variability. Our results suggest that oblique views should be used routinely in children with clinically suspected urinary tract infection to reliably interpret images.

Visualization of gallbladder with In-111 labeled octreotide in post prandial state.

Somatostatin receptor scintigraphy is widely used in the management of neuroendocrine tumors. Somatostatin receptors are present in both neoplastic and normal tissues, which may lead to misinterpretation of the scans. Here, a patient with lung carcinoid imaged with In-111 octreotide is presented. Imaging was performed 4 and 24 hours after an intravenous injection of 185 MBq In-111 octreotide in the post prandial state. Whole body and SPECT images showed accumulation of radioactivity in the gallbladder. Imaging was repeated after fatty meal ingestion to differentiate abnormal activity and physiological uptake in the gallbladder. The abdominal SPECT studies at 28 hours revealed no uptake in the gallbladder, and the scintigraphic study was reported as normal so further excessive diagnostic procedures were prevented. Gallbladder can be visualized on somatostatin receptor scintigraphy even in the post prandial state. Delayed images after fatty meal administration are important for differential diagnosis.

Role of scintigraphy in congenital thyroid anomalies.

Thyroid scintigraphy using Tc-99m pertechnetate is a frequently performed procedure in routine nuclear medicine practice. The indications for thyroid scintigraphy are investigation of hyperthyroidism, nodularity of the gland, cause of thyroid stimulating hormone elevation and localization of an ectopic thyroid gland. In the pediatric population, the most common request is for the evaluation of neonatal hypothyroidism. This imaging procedure is helpful in the identification of the underlying cause as well as in making a differential diagnosis. Early diagnosis is essential for appropriate therapy planning in this age group, and thyroid scintigraphy provides important diagnostic data. This article is written to review the scintigraphic findings in various congenital thyroid anomalies and to underline its use in the differential diagnosis.