Faint Uptake Research Articles

8135 A Rare Case of Late Recurrence of Graves’ Disease Decades After Radioactive Iodine Therapy: Is it Really a Definitive Treatment?

Abstract Disclosure: K.S. Hill: None. R. Osman: None. Graves’ disease (GD) is the most common cause of hyperthyroidism in the US and worldwide. Radioactive iodine (RAI) therapy has excellent success rates in treatment of GD. Studies have demonstrated that RAI successfully treats GD with a single session in the majority of cases. Recurrence after RAI, if it occurs, is most commonly seen in the first year after RAI. However, this is rare particularly in patients who have developed evidence of successful treatment in the form of post-ablative hypothyroidism. Only a few case reports have demonstrated recurrence of GD more than 10 years after treatment of GD with RAI and development of post-ablative hypothyroidism. We report a case of GD recurrence approximately 30 years after ablation. A 69 y/o woman presented for evaluation of hyperthyroidism and newly discovered thyroid nodule. Her history was significant for GD with orbitopathy diagnosed in the early 1990s and treated with RAI. Following the ablation, she developed hypothyroidism and was managed for over 20 years on levothyroxine therapy. In recent years she began to develop symptoms of palpitations and heat intolerance with biochemical evidence of thyrotoxicosis despite reductions in her levothyroxine dose. She also developed recurrence of her orbitopathy, confirmed by ophthalmology. During this time, a neck CT incidentally described an atrophic thyroid gland with a 9 mm soft tissue nodule in the left thyroid bed. Follow up ultrasound showed a 1.1 cm nodule with increased vascularity in the left thyroid bed with an otherwise atrophic gland and no lymphadenopathy. Her levothyroxine was stopped for one month in preparation for a thyroid uptake scan, during which TSH increased to 15 mcU/mL. Scan showed overall severely decreased radioactive iodine uptake of the gland consistent with prior ablation although there was a faint uptake most focally conspicuous on the left side inferiorly. Thyroid stimulating immunoglobulin (TSI) was elevated at 1.35 IU/L (Ref 0.00-0.55). After discussion with the patient, the decision was made for surgical treatment with thyroidectomy. Pathology was benign. She was continued on her prior dose of levothyroxine 75 mcg daily however now with clinical and biochemical evidence of hypothyroidism requiring continued increase in levothyroxine dose to normalize TSH levels. GD is the most common cause of hyperthyroidism and RAI therapy is the most common definitive treatment for GD in the US. Recurrence of GD after ablative hypothyroidism is rare, particularly in the case of late recurrence decades after ablation. Only a few cases are reported in the literature, ours with the longest interval-to-relapse. Recurrence of orbitopathy may be the first clue. Our case highlights the need to continue to monitor clinically for recurrence of Graves’ disease long after RAI use. Presentation: 6/3/2024

Exploratory Tau PET/CT with [11C]PBB3 in Patients with Suspected Alzheimer's Disease and Frontotemporal Lobar Degeneration: A Pilot Study on Correlation with PET Imaging and Cerebrospinal Fluid Biomarkers.

Accurately diagnosing Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) is challenging due to overlapping symptoms and limitations of current imaging methods. This study investigates the use of [11C]PBB3 PET/CT imaging to visualize tau pathology and improve diagnostic accuracy. Given diagnostic challenges with symptoms and conventional imaging, [11C]PBB3 PET/CT's potential to enhance accuracy was investigated by correlating tau pathology with cerebrospinal fluid (CSF) biomarkers, positron emission tomography (PET), computed tomography (CT), amyloid-beta, and Mini-Mental State Examination (MMSE). We conducted [11C]PBB3 PET/CT imaging on 24 patients with suspected AD or FTLD, alongside [11C]PiB PET/CT (13 patients) and [18F]FDG PET/CT (15 patients). Visual and quantitative assessments of [11C]PBB3 uptake using standardized uptake value ratios (SUV-Rs) and correlation analyses with clinical assessments were performed. The scans revealed distinct tau accumulation patterns; 13 patients had no or faint uptake (PBB3-negative) and 11 had moderate to pronounced uptake (PBB3-positive). Significant inverse correlations were found between [11C]PBB3 SUV-Rs and MMSE scores, but not with CSF-tau or CSF-amyloid-beta levels. Here, we show that [11C]PBB3 PET/CT imaging can reveal distinct tau accumulation patterns and correlate these with cognitive impairment in neurodegenerative diseases. Our study demonstrates the potential of [11C]PBB3-PET imaging for visualizing tau pathology and assessing disease severity, offering a promising tool for enhancing diagnostic accuracy in AD and FTLD. Further research is essential to validate these findings and refine the use of tau-specific PET imaging in clinical practice, ultimately improving patient care and treatment outcomes.

SAT555 Utility of 18F-DOPA PET/CT in the Diagnosis of Medullary Thyroid Cancer in a Patient with Multiple Endocrine Neoplasia Type 2B

Abstract Disclosure: D.G. Varghese: None. S. Akshintala: None. A. Jha: None. S. Gubbi: None. A. Reno: None. J. Klubo-Gwiezdzinska: None. K. Pacak: None. J. Glod: None. J. Del Rivero: None. Background: MEN2B is a cancer predisposition syndrome caused by an activating mutation in the RET proto-oncogene. It is characterized by medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and extra endocrine features. U/S, CT, MRI and 18F-fluorodeoxyglucose (18F-FDG), 18F-fluorodihyroxyphenylalanine (18F-FDOPA), 68Ga-DOTA-(0)-Tyr(3)-octreotate (68Ga-DOTATATE) PET/CT scans have been used for the diagnosis and follow up of MTC. However, there is increasing evidence of 18F-FDOPA PET as more specific imaging modality in the diagnosis of MTC since L-type amino acid transporters have shown to be present in MTC cells.Clinical Case: 26-year-old female presented with HTN at the age of 17. The patient developed episodes of nausea/vomiting, intermittent headaches with systolic BP in the 190’s. Further work-up revealed bilateral adrenal nodules with elevated plasma metanephrines. The patient underwent left adrenalectomy and a year later, right adrenal nodule resection confirming PHEO. On follow up, calcitonin was elevated, and the patient underwent a total thyroidectomy with bilateral central lymph node dissection. At age 19 she was diagnosed with MEN2B (RET mutation, p.Met918Thr). With rising calcitonin, she was referred to our institution for further evaluation. Her serum calcitonin was 31986(<7.6 pg/ml), CEA 631 (0.8-3.4 ng/ml), fractionated plasma normetanephrine 565 (18-112 pg/ml), and metanephrine 304 (12-61 pg/mL). MRI of the abdomen showed enlarging adrenal masses. 18F-FDG PET/CT scan showed a focus of uptake (SUVmax of 8.5) in posterior right thyroid bed, uptake in the liver (SUVmax of 7.5) and uptake in the right adrenal gland and left adrenal bed; 68Ga-DOTATATE PET/CT scan showed a faint uptake in the right thyroid lobe (SUVmax of 2.7) and an 18F-FDOPA PET/CT scan showed intense uptake in both lobe of the thyroid, multiple lesions in the liver and suspicious focus in the right adrenal bed. The patient underwent bilateral adrenalectomy for recurrent PHEO and her plasma metanephrines normalized. Conclusion: This case adds to the mounting evidence in the usage of 18F-FDOPA PET/CT scan as a useful imaging modality for MTC especially in the setting of MEN2B syndrome. A head-to-head comparison in 18 patients, both per patient and per lesion sensitivity by 18F-FDOPA PET/CT (72%, 85%) was found to be statistically superior compared to 68Ga-DOTATATE PET/CT (33%, 20%), and 18F-FDG PET/CT (17%, 28%). A meta-analysis conducted in MTC consisting of 306 patients from 14 studies, 18F-FDOPA compared to 18F-FDG and 68Ga-DOTATATE showed the highest surface under the cumulative ranking curve (SUCRA) value in both patient and lesion-based analyses irrespective of serum calcitonin/CEA values or calcitonin doubling time. The potential for use of 18F-FDOPA as a diagnostic agent and the potential to provide insight into possible therapeutic targets are unknown and should be further studied. Presentation Date: Saturday, June 17, 2023

Performances of 68Ga-PSMA PET-CT compared to 18F-FDOPA PET-CT to discriminate inflammatory radiation related changes from early recurrences in Glioblastoma's patients: Preliminary analysis

Discriminating recurrence from post-radiation related modification in patients with glioblastomas still remains challenging with morphological and functional imaging. The purpose of this pilot study was to assess the feasibility of 68Ga-PSMA PET/CT in detecting early recurrence, by comparison with 18F-FDOPA PET/CT. This was a non-randomized, prospective, multicentric feasibility study. Patients followed up for glioblastomas, with a MRI performed since the end of the radiotherapy until 12 months of follow up after the end of radiotherapy, were referred for both 68Ga-PSMA and 18F-FDOPA PET-CT, whatever the conclusion of the MRI (post radiation modifications, relapse or doubtful MRI). Nine patients from 2 centers were included. They were referred for both PET/CT which were realized the same day with a 6 hours delay. SUVmax, lesion-to-striatum ratio (TBR), lesion-to-normal parenchyma ratio (TNR), and lesion-to-salivary glands ratio (TSGR) were calculated. Among our nine patients, five patients demonstrated good correlation between 18F-FDOPA and 68Ga-PSMA PECT/CT findings. For four of these five patients, both examinations were consistent with recurrence, better visualized with PSMA, thanks to a better lesion-to-background ratio. Examinations of the fifth patient were suggestive of post radiation related changes. It was better analyzed with PSMA which displays a very faint uptake compared to DOPA. Conversely, four of our nine patients showed conflicting results. A recurrence was not detected by the PSMA because of a previously introduced bevacizumab treatment (false negative). For another patient, both examinations were consistent with recurrence, but there was an uptake mismatch regarding suspected lesion sites. This highlights distinct pathophysiological processes. Eventually, two patients presented inconsistent examinations, one patient with post radiation related remodeling (DOPA + PSMA−) and one suspected of recurrence (DOPA + PSMA−). Investigations are ongoing to try to explain these findings. Despite some scarce discrepancies between 68Ga-PSMA and 18F-FDOPA examinations, and the small number of patients included, this pilot study highlights the potential role of 68Ga-PSMA in helping to discriminate post-radiation inflammatory related modifications from glioblastoma recurrence in patients whithout recent bevacizumab treatment. The discrepancies are probably related to not fully understood distinct pathophysiological processes. False positives and false negatives could be minimised by following certain rules before carrying out the examination. 68Ga PSMA PET/CT seems useful because of its excellent lesion to background ratio. In case of positive PSMA recurrence, 177Lu PSMA could be considered as a new therapeutic alternative. However, more powerful prospective studies are needed to validate these results.

Temporal Evolution and Prognostic Role of Indeterminate Response Sub-Groups in Patients with Differentiated Thyroid Cancer after Initial Therapy with Radioiodine

The clinical outcome of patients affected by Differentiated Thyroid Carcinoma (DTC) and an indeterminate response (IR) after initial therapy is not yet clear. IR includes three different sub-groups of patients: (1) IRTg+ group: Detectable thyroglobulin (Tg), regardless of antithyroglobulin antibodies (TgAb) presence or imaging studies; (2) IRTgAb+ group: Positive TgAb, regardless of Tg levels and nonspecific imaging findings; (3) IRImaging+ group: Nonspecific findings on neck ultrasonography or faint uptake in the thyroid bed on the whole-body scan, negative TgAb, and undetectable Tg. The main aim of this retrospective study was to investigate the dynamic evolution and prognostic role of these patients. From January 2010 to December 2017, 2176 patients who received radioiodine for DTC after total thyroidectomy were included. Two-hundred-eighty-eight patients had IR one year after therapy (187 TgAb+, 76 Tg+, 25 imaging+). After two years, 110 patients (38%) were reclassified as an excellent response and 5 (2%) as an incomplete response; after five years, 221 (77%) achieved an excellent response and 11 (4%) showed an incomplete response. One-year stimulated Tg and nodal disease at diagnosis may predict the final status of the disease. Progression-free survival was significantly shorter in IRTg+ than in IRTgAb+ and IRimaging+ groups. Considering Tg+ patients, a threshold of 3.3 ng/mL is best to predict prognosis.

LBODP097 Malignant Struma Ovarii: Long Term Successful Treatment. Outcome

Abstract 18 year old African American female saw her GYN in 9/2008 for abdominal pain. CT: bilateral adnexal masses (10×8 cm left; 6.3×3.1 cm right). Surgical pathology reported a left benign cystic teratoma and right corpus luteum cyst. Pain recurred in 2010. MRI showed: 9×7.5×4 cm right adnexal mass. Repeat surgery was done. Pathology: benign cystic teratoma with focal thyroid tissue - "Struma Ovarii". Abdominal pain recurred yet again in 2012. Sonography revealed a mixed solid/cystic pelvic mass measuring 10.6×7.9×7.6 cm. Exploratory laparotomy 9/2012 revealed a right adnexal mass and widespread peritoneal nodules. Pathology reported follicular tissue with colloid in the nodules - "Peritoneal Strumatosis" suggesting benignity. Upon further review was reclassified as metastatic well differentiated follicular thyroid cancer of ovarian origin with follicular thyroid tissue identified in peritoneal lymph nodes, spleen, bladder and rectal wall. The patient was then referred to endocrinology at our facility. On exam she was clinically euthyroid without thyromegaly or nodularity. Thyroid hormone levels were normal. Antithyroid antibodies were absent. Serum Thyroglobulin (Tg): elevated (229; normal 2-35 ng/ml) as was CA125 (64; normal <21 U/ml). Immunohistochemistry: positive for Tg and Thyroid transcription factor-1. Molecular markers: no mutations in BRAF, RAS, or TP53. In preparation for radioactive iodine (RAI) therapy, total thyroidectomy was performed 4/13/2013 and reported as normal thyroid tissue. Dosimetry findings: very iodine avid tissue with prolonged retention (33% at 6 days). Maximum tolerated dose: 200 mCi. A 62.8 mCi RAI was administered 7/13/2013. Post RAI whole body scan (WBS): numerous focal areas of increased uptake in abdomen and pelvis consistent with metastatic disease. Treatment with L-thyroxine was given to suppress TSH. Follow up WBS 12/26/2013 showed persistent increased uptake in abdomen and pelvis. Serum Tg was high (198. 0). A second RAI dose of 104.8 mCi was given. Post RAI WBS confirmed multiple areas of metastatic disease in abdomen and pelvis. Subsequent serum Tg levels down trended. WBS 11/12/2014: only two residual abnormal foci in the lower neck and one inferior to the liver without abdominal or pelvic foci. Given the dosimetry issue and the reassuring serum Tg levels, surveillance was continued. WBS 9/25/2015: unchanged. Now age 27, WBS 1/26/2022: only residual faint lower neck uptake, resolution of the focus inferior to the liver and no distant foci. Stimulated Tg was normal at 2.2 ng/ml with stimulated TSH >110. 0 uIU/ml. Presentation: No date and time listed

OLD WOUNDS RUN DEEP: A CASE OF THORACIC SPLENOSIS FOLLOWING REMOTE TRAUMA

TOPIC: Disorders of the Pleura TYPE: Medical Student/Resident Case Reports INTRODUCTION: Thoracic splenosis develops as a result of auto-transplantation of splenic tissue into the thoracic cavity following splenic and diaphragmatic injury. Less than 40 cases have been reported in the literature so far and it remains an elusive diagnosis.[1] The majority of cases were asymptomatic and presented as incidental findings on imaging. Few cases reported symptoms like pleuritic chest pain, hemoptysis, and phrenic nerve irritation that prompted a diagnostic workup. [2] We report one such case in which a young female with penetrating abdominal trauma and unexplained shortness of breath was diagnosed with thoracic splenosis. CASE PRESENTATION: Our patient is a 32-year-old female who presented for evaluation of lung nodules found on work-up for recurrent dyspnea. She had previously been treated for suspected bronchitis, however, complained of persistent exertional dyspnea, orthopnea, and fatigue. She denied any chest pain, fever, chills, cough, pedal edema, or weight loss. She had a history of a gunshot to the abdomen that resulted in splenectomy 8 years prior to presentation. Physical exam was unremarkable and bloodwork was normal. Chest x-ray showed pleural irregularities computed tomography revealed nodularity of the left pleural space. PET-CT revealed faint uptake in this area. Transthoracic biopsy of the pleura yielded an acellular specimen. Thoracic splenosis was suspected, and liver and spleen imaging with single-photon emission computed tomography was performed after injecting 5.7 mCi Tc-99m sulfur colloid. The study showed multiple foci of uptake corresponding with underlying soft tissue nodules in the left lower pleura, left lower chest wall, and bilateral mesentery. A diagnosis of thoracic splenosis secondary to penetrating trauma was made. The patient's spirometry was normal and she was managed with supportive care and reassurance. DISCUSSION: The diagnosis of thoracic splenosis can be challenging as there can be a significant lag between thoracoabdominal trauma and chest findings. The Tc-99 m heat-damaged erythrocyte scan has high sensitivity and specificity for splenic tissue, while Tc-99m sulfur colloid and indium-111-labeled platelets are less sensitive alternatives. CT-guided biopsies and needle aspirations typically have a poor yield and increased risk of bleeding. [4,5] As splenic tissue is slow-growing, non-invasive, and mostly asymptomatic, appropriate management is observation and reassurance. Surgical removal carries a significant risk of morbidity and is only attempted in patients with severe, persistent symptoms or increasing size of the mass. [3] CONCLUSIONS: Thoracic splenosis can be diagnosed with a thorough history and appropriate imaging, but patients often undergo invasive procedures such as bronchoscopy or surgery in order to rule out a neoplasm. Pulmonologists should be aware of this rare entity in order to avoid unnecessary procedures REFERENCE #1: Ha YJ, Hong TH, Choi YS. Thoracic Splenosis after Splenic and Diaphragmatic Injury. Korean J Thorac Cardiovasc Surg. 2019;52(1):47-50. doi:10.5090/kjtcs.2019.52.1.47 REFERENCE #2: Le Bars F, Pascot R, Ricordel C, et al. Thoracic splenosis: Case report of a symptomatic case. Chin J Traumatol. 2020;23(3):185-186. doi:10.1016/j.cjtee.2020.05.003 REFERENCE #3: Matthews A, Chesser M, Mand J, Thomas A. A Growth Opportunity: Thoracic Splenosis. Am J Med. 2017;130(4):420-422. doi:10.1016/j.amjmed.2016.11.010 DISCLOSURES: No relevant relationships by Sukhmani Boparai, source=Web Response No relevant relationships by David Chambers, source=Web Response No relevant relationships by Deon Ford, source=Web Response No relevant relationships by Prathik Krishnan, source=Web Response No relevant relationships by Shreedhar Kulkarni, source=Web Response No relevant relationships by Jonathan Packer, source=Web Response

Thyroglobulin Antibodies as a Prognostic Factor in Papillary Thyroid Carcinoma Patients with Indeterminate Response After Initial Therapy.

The clinical outcome of papillary thyroid carcinoma (PTC) patients with an indeterminate response after initial therapy is reported to be intermediate, between incomplete and excellent responses. This study evaluated the outcomes of PTC patients with indeterminate response after initial therapy. It was further determined whether the indeterminate findings predicted outcomes more precisely. Patients were further classified into 3 groups based on risk of structural persistence/recurrence: Tg group: detectable thyroglobulin, negative antithyroglobulin antibody, regardless nonspecific imaging findings; TgAb group: positive antithyroglobulin antibody, regardless thyroglobulin levels and nonspecific imaging findings, and Image group: nonspecific findings on neck ultrasonography or faint uptake in the thyroid bed on whole-body scan, undetectable thyroglobulin and negative antithyroglobulin antibody. Sixty-six patients aged 44.1±12.7 years were studied, of whom 58 (87.9%) were females. All patients underwent total thyroidectomy, and 52 patients (78.8%) received radioiodine. After 5.7 years (P25-75 2.6-9.75 years) of follow-up, most patients (89.4%) were reclassified as having an excellent response or remained in the indeterminate response to therapy. Structural recurrence/persistence disease was detected in 7 (10.6%) patients. The persistence/recurrence rate in groups were as follow: Tg, 2.63%; TgAb, 31.25%; Image, 8.3% (p=0.007). The 10-years disease-free survival rate in the TgAb group was significantly reduced (p=0.022). Our results suggest that patients with PTC and indeterminate response due to positive serum antithyroglobulin antibody have more risk of development of structural disease. These findings suggest a more individualized follow-up strategy for patients with an indeterminate response.

Feasibility and variability of corneal esthesiometry in Hermann's tortoises (Testudo hermanni) depending on age and body weight

ABSTRACT Background Hermann's tortoise is one of the most popular reptiles kept as pet which underlines the importance to reinforce the information needed to provide advanced and adequate veterinary care in exotic animal species. Therefore, the purpose of this study, performed in Testudo hermanni, was to evaluate corneal touch threshold (CTT) and its feasibility according to age and body weight. Methods Fifty-one healthy tortoises were classified in 2 groups (≤2 years [young; n = 25] and 8–10 years [subadult; n = 26]). Central CTT was measured by means of a Cochet-Bonnet esthesiometer and defined as the filament length required to elicit a blink in at least 3/5 applications. CTT feasibility according to body weight was also evaluated by diving the individuals in weight groups consisting of “lighter” ( Results Mean CTT was 5.99 cm for the whole population (90% CI: 5.87–6.11), being 5.98 cm for young (90% CI: 5.81–6.15) and 6 cm for all subadult (90% CI: 6.00–6.00) tortoises, and 5.98 cm for lighter (90% CI: 5.84–6.13) and 6 cm for all heavier (90% CI: 6.00–6.00) tortoises. No statistical differences were detected between age and weight groups (P = 0.159 and P = 0.159, respectively). Three animals presented unilateral faint fluorescein uptake postesthesiometry (3/51; 2.9%) that resolved spontaneously within 48 hours. Conclusions and clinical relevance Cochet-Bonnet esthesiometer was a safe means of confirming high corneal sensitivity in all tortoises, which was high regardless of age. Increasing filament lengths would ultimately be required to determine the true corneal sensitivity scope of Testudo hermanni.

Efficacy of low radioiodine activity versus intermediate-high activity in the ablation of low-risk differentiated thyroid cancer.

The aim of our study was to compare the efficacy of thyroid remnant ablation using low (1.1 GBq) and intermediate-high radioiodine (RAI) activity (1.85-3.7 GBq) in low-risk differentiated thyroid carcinoma (DTC) and to evaluate the staging role of the whole body scan (WBS) in detection extrathyroidal disease. We retrospectively included 277 patients who underwent total thyroidectomy and RAI for low-risk DTC and divided them in two groups according to RAI activity at ablation: group 1 (n = 174) treated with low activity (1.1 GBq), and group 2 (n = 103) with intermediate-high activity (1.85-3.7 GBq). To evaluate the successful ablation rate, the WBS 1 year after RAI was visually interpreted using a three-point scale: score 0 in case of absence of visible RAI uptake in thyroid bed; score 1 in presence of faint uptake in the thyroid bed; and score 2 in case of significant RAI uptake in thyroid bed. The success ablation rate was significantly higher in group 2 than group 1 (p < 0.001) with the presence of a positive WBS (score 1-2) in 65% low-activity group and 33% in intermediate-high group. Considering response to therapy categories, excellent response rate was significantly higher in group 2 (p = 0.020), while indeterminate response was higher in group 1 (p value = 0.005). Post RAI imaging revealed extrathyroidal uptake in 27 cases: 17 laterocervical nodal and 10 distant metastases. In both groups similar detection rate of nodal and distant metastases were recognized without any statistical difference. The ablation rate with intermediate-high RAI activity (1.85-3.7 GBq) was better than with a low activity (1.1 GBq). First WBS may help to recognize nodal and distant metastases in about 10% of cases changing clinical stage and subsequent management.

Pathological complete response after afatinib treatment of stage IV oligometastatic adenocarcinoma of the lung: the role of pulmonary surgery

BackgroundSome oligometastatic lung cancer patients, after induction systemic chemotherapy or tyrosine kinases inhibitor treatment, followed by aggressive radical consolidative treatment, have improved overall survival. Unfortunately, clinical criteria cannot assess such patients.Case presentationWe hereby reported the case of a 55-year-old female with lower back pain and bilateral lower leg numbness for months and who had an osteolytic bone lesion over the third lumbar vertebra. In February 2017, a third lumbar vertebra biopsy showed metastatic adenocarcinoma, compatible with lung origin (thyroid transcription factor-1 positive [TTF-1], L858R mutation positive). Complete imaging of the right lower lobe (RLL) showed a spiculated mass of about 3.4 × 2.2 cm, and a trans-bronchoscopic lung biopsy revealed non-small cell carcinoma of lung origin (positive for TTF-1 and negative for p40). Tentative diagnosis was RLL adenocarcinoma, cT2aN0M1b, with bone metastasis at L3. The epidermal growth factor receptor-tyrosine kinase inhibitor afatinib was prescribed beginning April 2017. A November 2018 follow-up CT scan showed regression in the RLL lung mass. A whole-body positron emission tomography-computed tomography showed RLL lung nodule with faint uptake and mildly increased uptake in the L3 vertebra. After providing informed consent, the patient received uniportal video-assisted thoracoscopic RLL lobectomy and radical mediastinal lymph node dissection on December 25, 2018. The final pathology report was fibrotic scar with no residual tumor cells, compatible with post-treatment status, ypT0N0. Curative intent radiotherapy was also applied to the L3 vertebra after the operation. The patient is still alive for more than 32 months after initially diagnosed with metastatic lung adenocarcinoma.ConclusionsOur case provides additional data to support that tissue assessment through primary lung tumor resection after systemic treatment of oligometastic lung cancer by minimally invasive surgery can reveal the treatment effect and potentially provide a surrogate endpoint in further clinical trials.

Risk Factors for Indeterminate Response After Radioactive Iodine Therapy in Patients With Differentiated Thyroid Cancer.

We investigated the risk factors of indeterminate response (IDR) in patients who underwent recombinant human thyroid-stimulating hormone (rhTSH)-aided radioactive iodine therapy (RAIT). A total of 128 patients with papillary thyroid cancer were included in this retrospective study. The patients were classified into excellent response and IDR groups based on follow-up diagnostic whole-body scintigraphy (WBS) and TSH-stimulated thyroglobulin (Tg). Indeterminate response was defined as the presence of a faint uptake in the thyroid bed on the diagnostic WBS or a TSH-stimulated Tg detectable, but less than 10 ng/mL. Parameters that act as significant risk factors for IDR, including age, sex, stage, surgeon, time interval between surgery and RAIT, post-treatment WBS finding, urine iodine-to-creatinine ratio, TSH-unstimulated Tg, and rhTSH-stimulated Tg, were analyzed using a Cox proportional hazards regression method. After treatment, 64 patients showed IDR. Recombinant human TSH-stimulated Tg was the only independent risk factor for predicting IDR. Patients with an rhTSH-stimulated Tg greater than 2 ng/mL prior to RAIT were 3.75 times more likely (95% confidence interval, 1.61-8.72) to have an IDR than those with a lower rhTSH-stimulated Tg (≤2 ng/mL). Pre-RAIT TSH-stimulated Tg levels are a risk factor for IDR after RAIT.

Preliminary results of biodistribution and dosimetric analysis of [68Ga]Ga-DOTAZOL: a new zoledronate-based bisphosphonate for PET/CT diagnosis of bone diseases.

Pre-clinical studies with gallium-68 zoledronate ([68Ga]Ga-DOTAZOL) have proposed it to be a potent bisphosphonate for PET/CT diagnosis of bone diseases and diagnostic counterpart to [177Lu]Lu-DOTAZOL and [225Ac]Ac-DOTAZOL. This study aims to be the first human biodistribution and dosimetric analysis of [68Ga]Ga-DOTAZOL. Five metastatic skeletal disease patients (mean age: 72 years, M: F; 4:1) were injected with 150-190MBq (4.05-5.14mCi) of [68Ga]Ga-DOTAZOL i.v. Biodistribution of [68Ga]Ga-DOTAZOL was studied with PET/CT initial dynamic imaging for 30min; list mode over abdomen (reconstructed as six images of 300s) followed by static (skull to mid-thigh) imaging at 45min and 2.5h with Siemens Biograph 2 PET/CT camera. Also, blood samples (8 time points) and urine samples (2 time points) were collected over a period of 2.5h. Total activity (MBq) in source organs was determined using interview fusion software (MEDISO Medical Imaging Systems, Budapest, Hungary). A blood-based method for bone marrow self-dose determination and a trapezoidal method for urinary bladder contents residence time calculation were used. OLINDA/EXM version 2.0 software (Hermes Medical Solutions, Stockholm, Sweden) was used to generate residence times for source organs, organ absorbed doses and effective doses. High uptake in skeleton as target organ, kidneys and urinary bladder as organs of excretion and faint uptake in liver, spleen and salivary glands were seen. Qualitative and quantitative analysis supported fast blood clearance, high bone to soft tissue and lesion to normal bone uptake with [68Ga]Ga-DOTAZOL. Urinary bladder with the highest absorbed dose of 0.368mSv/MBq presented the critical organ, followed by osteogenic cells, kidneys and red marrow receiving doses of 0.040, 0.031 and 0.027mSv/MBq, respectively. The mean effective dose was found to be 0.0174mSv/MBq which results in an effective dose of 2.61mSv from 150MBq. Biodistribution of [68Ga]Ga-DOTAZOL was comparable to [18F]NaF, [99mTc]Tc-MDP and [68Ga]Ga-PSMA-617. With proper hydration and diuresis to reduce urinary bladder and kidney absorbed doses, it has clear advantages over [18F]NaF owing to its onsite, low-cost production and theranostic potential of personalized dosimetry for treatment with [177Lu]Lu-DOTAZOL and [225Ac]Ac-DOTAZOL.

Individualized Follow-Up Strategy for Patients with an Indeterminate Response to Initial Therapy for Papillary Thyroid Carcinoma.

The concept of a dynamic risk-stratification scheme has been suggested for individualized management of patients with papillary thyroid carcinoma (PTC). However, there is no specified follow-up strategy for patients with an indeterminate response. This study evaluated 403 PTC patients who had an indeterminate response during the first 12-24 months after initial therapy. All patients underwent total thyroidectomy with radioactive iodine remnant ablation. Patients were further classified into three groups based on risk of structural persistence/recurrence: a Tg+ group (detectable thyroglobulin [Tg], regardless of antithyroglobulin antibody [TgAb] or imaging findings; 196 patients), a TgAb+ group (positive results for TgAb with undetectable Tg, regardless of imaging findings; 46 patients), and an Image+ group (nonspecific findings on neck ultrasonography or faint uptake in the thyroid bed on whole-body scan, with undetectable Tg and negative results for TgAb; 161 patients). With a median of 9.6 years (interquartile range 7.7-11.2 years) of follow-up, 56 (14%) PTC patients had structural persistent/recurrent disease: 50 (89%) at locoregional sites and six (11%) at distant sites. The recurrence rate in Tg+, TgAb+, and Image + groups were 26.5%, 8.7%, and 0%, respectively. The median time to detection of structural persistent/recurrent disease from the initial thyroid surgery was 3.7 years (interquartile range 2.5-6.3 years). The optimal cutoff stimulated Tg level to predict structural persistent/recurrent disease was 3.1 ng/mL in the Tg+ group. This classification system revealed higher predictability of structural persistent/recurrent disease than the tumor-node-metastasis staging system and American Thyroid Association risk stratification (proportion of variation explained: 15.7% vs. 2.4% and 0.9%, respectively). Six (3%) patients with distant metastatic disease were all classified in the Tg+ group, and all had lung metastasis. The findings suggest a more individualized follow-up strategy for patients with an indeterminate response. More careful evaluation, including early evaluation of distant metastasis, is necessary in patients with elevated Tg levels. However, for patients testing positive for TgAb or those with only nonspecific imaging findings, regular follow-ups of Tg and TgAb levels and neck ultrasonography are sufficient.

Assessing 18F-FDG Uptake in the Sentinel Lymph Node in Breast Cancer.

18F-FDG PET/CT has limited value in early breast cancer. Sentinel lymph node (SLN) biopsy is the current procedure of choice to search for small metastatic deposits in the axillary lymph nodes in early breast cancer. In this retrospective study, we reevaluated 18F-FDG PET/CT images after locating the SLN on PET/CT with the help of SLN SPECT/CT images and assessed 18F-FDG uptake, particularly in the SLN. Our goal was to understand if combined evaluation of 18F-FDG PET/CT and SLN SPECT/CT could be useful for detecting early lymph node metastasis in the axilla. Methods: 18F-FDG PET/CT images of newly diagnosed breast cancer patients who also had SLN scintigraphy (SPECT/CT) and biopsy results were analyzed to assess 18F-FDG uptake in the SLN. The SLN seen on SPECT/CT images was located on PET/CT images, and its metabolic activity was assessed both visually and semiquantitatively using SUVmax 18F-FDG PET results were compared with the histopathology result for the SLN. Results: Twenty patients among 130 met the inclusion criteria. SLN SPECT/CT images were helpful for locating the SLN on 18F-FDG PET/CT images in all 20 patients. Histopathologic analysis of the SLNs demonstrated metastasis in 7 patients and no metastasis in 13. There was mild (visible) 18F-FDG uptake in the SLN (SUVmax, 1.2-4.1; metastatic deposit size, 6-8 mm) in 6 of 7 patients with SLN metastasis (85.7%). There was no or only faint 18F-FDG uptake in the SLN (SUVmax < 1) in 9 of 13 patients with no SLN metastasis (69.2%). Receiver-operating-characteristic curve analysis indicated that the SUVmax cutoff for differentiating SLN-positive from -negative cases was 0.85 (sensitivity, 85.7%; specificity, 61.5%; area under the curve, 0.747; P < 0.05). Conclusion: Combined evaluation of 18F-FDG PET/CT and SPECT/CT images to assess 18F-FDG uptake, particularly in the SLN, is a new image analysis technique to detect early metastatic disease in the axillary lymph nodes in breast cancer. Although this technique does not currently seem feasible for use in routine practice, mainly because of the limitations of current PET/CT technology in detecting small tumors, it is an interesting image analysis technique to be aware of for possible future use.

Aggressive differentiated thyroid cancer with multiple metastases and NRAS and TERT promoter mutations: A case report

Sorafenib, a tyrosine kinase inhibitor, is approved for the treatment of advanced differentiated thyroid carcinoma (DTC). Resistance to sorafenib may appear under treatment and may be associated with increased aggressiveness of the neoplasia. The present study reports the case of a 65-year-old male who underwent total thyroidectomy for a follicular thyroid carcinoma, Hürthle cell variant, in February 2005. Until January 2010, the patient received four consecutive 131I doses (total dose, 612 mCi) for increased serum thyroglobulin (Tg) and initial faint lung uptake (which eventually became undetectable). Subsequently, the patient developed several sequential bone (humerus, rib and skull), adrenal and lung metastases, the majority of which were surgically removed. Histological examination in all cases revealed evidence of DTC metastases that were strongly positive for Tg, as revealed by immunohistochemistry. In March 2014, sorafenib therapy was initiated, but it was discontinued 10 months later to allow an undelayable prostatectomy. Immediately upon surgery, the patient developed a large metastatic lesion in the right gluteal muscle, whose biopsy revealed undifferentiated neoplasia of epithelial origin, and the patient succumbed shortly afterwards. An extensive comparative search for biochemical and molecular markers was performed on all available tissues (primary tumor, and differentiated and undifferentiated metastases). The primary tumor and all the available metastases exhibited the same molecular oncogenic markers (namely, the RAS mutation p.Q61R and the telomerase promoter mutation C228T). In addition, the undifferentiated metastasis exhibited a p53 mutation. The present study reports a case of a sudden acceleration of DTC metastatic progression following sorafenib discontinuation, which could have been due to the emergence of sorafenib-resistant undifferentiated p53-positive tumor cell clones.

Pictorial review of 18F-FDG PET/CT findings in musculoskeletal lesions.

We herein reviewed 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) findings in a number of musculoskeletal lesions including malignant tumors, benign tumors, and tumor-like lesions with correlations to other radiographic imaging modalities, and described the diversity of the 18F-FDG PET/CT findings of this entity. Malignant primary musculoskeletal tumors are typically 18F-FDG avid, whereas low-grade malignant tumors show mild uptake. Benign musculoskeletal tumors generally show a faint uptake of 18F-FDG, and tumor-like conditions also display various uptake patterns of 18F-FDG. Although musculoskeletal tumors show various uptakes of 18F-FDG on PET/CT, its addition to morphological imaging modalities such as CT and MRI is useful for the characterization and differentiation of musculoskeletal lesions.

Diagnostic performance of a computer-assisted diagnosis system for bone scintigraphy of newly developed skeletal metastasis in prostate cancer patients: search for low-sensitivity subgroups

PurposeThe computer-assisted diagnostic system for bone scintigraphy (BS) BONENAVI is used to evaluate skeletal metastasis. We investigated its diagnostic performance in prostate cancer patients with and without skeletal metastasis and searched for the problems.MethodsAn artificial neural network (ANN) value was calculated in 226 prostate cancer patients (124 with skeletal metastasis and 101 without) using BS. Receiver operating characteristic curve analysis was performed and the sensitivity and specificity determined (cutoff ANN = 0.5). Patient’s situation at the time of diagnosis of skeletal metastasis, computed tomography (CT) type, extent of disease (EOD), and BS uptake grade were analyzed. False-negative and false-positive results were recorded.ResultsBONENAVI showed 82% (102/124) of sensitivity and 83% (84/101) specificity for metastasis detection. There were no significant differences among CT types, although low EOD and faint BS uptake were associated with low ANN values and low sensitivity. Patients showed lower sensitivity during the follow-up period than staging work-up. False-negative lesions were often located in the pelvis or adjacent to it. They comprised not only solitary, faint BS lesions but also overlaying to urinary excretion.ConclusionsBONENAVI with BS has good sensitivity and specificity for detecting prostate cancer’s osseous metastasis. Low EOD and faint BS uptake are associated with low sensitivity but not the CT type. Prostate cancer patients likely to have false-negative results during the follow-up period had a solitary lesion in the pelvis with faint BS uptake or lesions overlaying to urinary excretion.

68Ga-PSMA-HBED Uptake on Cervicothoracic (Stellate) Ganglia, a Common Pitfall on PET/CT.

Ga-PSMA-HBED PET/CT showed promising results in staging and restaging of prostate cancer. However, nonspecific uptake has been reported in the celiac ganglia. In this case series, we showed faint radiotracer uptake on upper thoracic region in the location of cervicothoracic (stellate) ganglia. This ganglion is located anterior to the transverse process of C7 vertebra, inferior to subclavian artery, and superior to the neck of the first rib.

Prognostic Value of Bone Marrow Tracer Uptake Pattern in Baseline PET Scans in Hodgkin Lymphoma: Results from an International Collaborative Study.

PET/CT-ascertained bone marrow involvement (BMI) constitutes the single most important reason for upstaging by PET/CT in Hodgkin lymphoma (HL). However, BMI assessment in PET/CT can be challenging. This study analyzed the clinicopathologic correlations and prognostic meaning of different patterns of bone marrow (BM) 18F-FDG uptake in HL. Methods: One hundred eighty newly diagnosed early unfavorable and advanced-stage HL patients, all scanned at baseline and after 2 adriamycin-bleomycin-vinblastine-dacarbazine (ABVD) courses with 18F-FDG PET, enrolled in 2 international studies aimed at assessing the role of interim PET scanning in HL, were retrospectively included. Patients were treated with ABVD × 4-6 cycles and involved-field radiation when needed, and no treatment adaptation on interim PET scanning was allowed. Two masked reviewers independently reported the scans. Results: Thirty-eight patients (21.1%) had focal lesions (fPET+), 10 of them with a single (unifocal) and 28 with multiple (multifocal) BM lesions. Fifty-three patients (29.4%) had pure strong (>liver) diffuse uptake (dPET+) and 89 (48.4%) showed no or faint (≤liver) BM uptake (nPET+). BM biopsy was positive in 6 of 38 patients (15.7%) for fPET+, in 1 of 53 (1.9%) for dPET+, and in 5 of 89 (5.6%) for nPET+ dPET+ was correlated with younger age, higher frequency of bulky disease, lower hemoglobin levels, higher leukocyte counts, and similar diffuse uptake in the spleen. Patients with pure dPET+ had a 3-y progression-free survival identical to patients without any 18F-FDG uptake (82.9% and 82.2%, respectively, P = 0.918). However, patients with fPET+ (either unifocal or multifocal) had a 3-y progression-free survival significantly inferior to patients with dPET+ and nPET+ (66.7% and 82.5%, respectively, P = 0.03). The κ values for interobserver agreement were 0.84 for focal uptake and 0.78 for diffuse uptake. Conclusion: We confirmed that 18F-FDG PET scanning is a reliable tool for BMI assessment in HL, and BM biopsy is no longer needed for routine staging. Moreover, the interobserver agreement for BMI in this study proved excellent and only focal 18F-FDG BM uptake should be considered as a harbinger of HL.