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Introduction Therapeutic options for metastatic paraganglioma (PGL) are limited, especially in the presence of uncontrolled secondary hypertension (HTN). Early findings from Lutetium-177 (Lu-177) DOTATE show promise for efficacy, although data on HTN control and survival are uncertain. Herein, we presented the successful treatment of a patient with metastatic PGL and uncontrolled HTN with Lu-177 DOTATE. Clinical Case A 16-year-old woman was admitted to the emergency department with severe headache, nausea and vomiting. She also reported stomach and low back pain for three months. The patient's blood pressure was 220/140 mmHg and a sodium nitroprusside infusion was started to treat the hypertensive crisis. On physical examination she had abdominal tenderness. A computer tomography (CT) examination revealed 6 cm mass, multiple metastatic nodular lesions in the lung and liver, as well as lytic lesions in all bones, and metastatic lymph nodes in thorax and abdomen. She is referred to our department for further evaluation HTN. Laboratory examinations revealed that plasma norepinephrine 24926 ng/L (70–480), 24-hour urine norepinephrine 1335 µg/day (20–81), metanephrine 534 µg/day (52–341), 3-metoksitiramine 771 µg/day (0–451), normetanephrine 20456 µg/day (88–444). Other laboratory findings were normal range. MIBG I131 scan which showed pathological uptake of MIBG was demonstrated in the regions described on CT. Genetic panel by next-generation sequencing (NGS) identify germline mutation and she had heterozygous mutations in SHDB (c.725 G>A) and BUB1B (c.1378 C>T). Surgical treatment was performed, and pathological finding reported 6cm mass, Ki-67 labeling index: %2, chromogranin A diffuse positive and there was vascular invasion. It was confirmed to be malignant PGL. 131I-MIBG therapy couldn't be given because of drugs interaction that used by patient. She received 13 cycles chemotherapy (cyclophosphamide, vincristine, dacarbazine) and palliative radiotherapy to metastatic bone lesions. She continued, however, to suffer from low back pain and HTN. Rising plasma and urine catecholamine levels. Therefore, conventional chemotherapy had been discontinued and he was commenced on Lu-DOTATATE therapy. Up to now, she has received 2 cycles at intervals of three months. Her clinical response was excellent with gradual improvement of symptoms and quality of life. Blood pressure is now within normal values without medication. There was significant reduction in the size of overall metastatic disease on Ga-68 DOTATE scanning. Conclusion Lu-177 DOTATE has potential advantages (drug interaction, radiation-safety) compared with 131I-MIBG therapy and chemotherapy. Our case demonstrates significant clinical and biochemical success in patients with metastatic PGL in addition to excellent disease management with low toxicity from PRRT. Lu-177 DOTATATE therapy is an effective and safe modality of treatment for patients with metastatic PGL.

An individual patient meta-analysis followed 1216 patients with PSA-only recurrence (biochemical recurrence, BCR) restaged with [68Ga]Ga-PSMA-11 PET/CT before the salvage treatment for median 3.5 years and analyzed the overall survival (OS). A new risk model included a good risk group with a prescan PSA < 0.5 ng/mL (26%), an intermediate risk group with a prescan PSA > 0.5 ng/mL and a PSMA PET/CT with 1 to 5 positive sites (65%), and a poor risk group with a prescan PSA > 0.5 ng/mL and a PSA PET/CT with > 5 positive sites (9%) (p < 0.0001, log rank test). The poor risk group had a five-year OS > 60%. Adding a BCR risk score by the European Association of Urology did not significantly improve the prediction of OS (p = 0.64). In conclusion, the restaging PSMA PET/CT markedly predicted the 5-year OS. The new risk model for patients with PSA-only relapse requires a restaging PSMA PET/CT for patients with a prescan PSA > 0.5 ng/mL and has a potential use in new trials aiming to improve the outcome for patients with PSA-only recurrence who have polysites prostate cancer detected on PSMA PET/CT.

Background Defining the extent of disease spread with imaging modalities is crucial for therapeutic decision-making and definition of treatment. This study aimed to investigate whether clinical parameters and nomograms predict prostate-specific membrane antigen (PSMA)-positive lymph nodes in treatment-naive nonmetastatic prostate cancer (PC) patients. Materials and methods The clinical data of 443 PC patients (83.3% high-risk and 16.7% intermediate-risk) were retrospectively analyzed. Receiver operating characteristic (ROC) curves with areas under the curve (AUC) were generated to evaluate the accuracy of clinical parameters (prostate-specific antigen [PSA], T stage, Gleason score [GS], International Society of Urological Pathology [ISUP] grade) and nomograms (Roach formula [RF], Yale formula [YF], and a new formula [NF]) in predicting lymph node metastasis. The AUCs of the various parameters and clinical nomograms were compared using ROC and precision-recall (PR) curves. Results A total of 288 lymph node metastases were identified in 121 patients (27.3%) using 68 Ga-PSMA-11-positron emission tomography (PET)/computed tomography (CT). Most PSMA-avid lymph node metastases occurred in external or internal iliac lymph nodes (142; 49.3%). Clinical T stage, PSA, GS, and ISUP grade were significantly associated with PSMA-positive lymph nodes according to univariate logistic regression analysis. The PSMA-positive lymph nodes were more frequently detected in patients with PSA >20 ng/ml, GS ≥7 or high risk disease compared to their counterparts. The clinical T stage, serum PSA level, GS, and ISUP grade showed similar accuracy in predicting PSMA-positive metastasis, with AUC values ranging from 0.675 to 0.704. The median risks for PSMA-positive lymph nodes according to the RF, YF, and NF were 31.3% (range: 12.3%-100%), 22.3% (range: 4.7%-100%), and 40.5% (range: 12.3%-100%), respectively. The AUC values generated from ROC and PR curve analyses were similar for all clinical nomograms, although the RF and YF had higher accuracy compared to NF. Conclusion The clinical T stage, PSA, GS, and ISUP grade are independent predictors of PSMA-positive lymph nodes. The RF and YF can be used to identify patients who can benefit from 68 Ga-PSMA-11 PET/CT for the detection of lymph node metastasis. Together with nomograms, 68 Ga-PSMA-11 PET/CT images help to localize PSMA-positive lymph node metastases and can thus assist in surgery and radiotherapy planning.

Ultrasonography is the most commonly used and most effective imaging modality in thyroid cancer imaging. It is the most successful method for evaluating primary tumor and local disease. I-131 scintigraphy is also a useful method in evaluating the whole body, but lacks anatomical detail. The absence of radioiodine uptake in 30-40% of patients also reduces the reliability of the test. These imaging methods alone are insufficient, especially in advanced stage and aggressive thyroid cancer subtypes. In this article, the additional roles, advantages and limitations of the several other imaging techniques, which are used for thyroid cancer staging and follow-up, will be discussed.

Tumor sink effect (TSE) has been defined as; decreased uptake in healthy tissue with increased tumor sequestration of the radiopharmaceuticals. It enables us to give high tumoral radiation doses while resulting in lower absorbed radiation to critical organs. However, the factors which influence this effect are yet to be defined. In this study, we have investigated the predictive factors of the tumor sink effect in a group of patients who received 177Lu-Prostate-specific membrane antigen (PSMA) therapy due to progressive metastatic castration-resistant prostate cancer (mCRPC). We have retrospectively analyzed the pre-therapy 68Ga-PSMA positron-emission tomography (PET)-computed tomography (CT) and post-therapy planar whole-body scans of 65 patients who received at least two cycles of 7.4 GBq of 177Lu-PSMA therapy. All patients with mCRPC were referred to our department after multiple treatment lines. Age, previous therapies, International Society of Urological Pathology (ISUP) score, and pre-therapy serum tumor marker levels were recorded. Post 177Lu-PSMA therapy images were analyzed for TSE. 68Ga-PSMA PET-CT images were used for the calculation of SUVmax in malignant and healthy tissues as well as metabolic tumor volume (MTV) and total lesion PSMA index (TLPI). Based on the post-therapy scans, TSE was seen in 17/65 (26.2%) patients. In univariate analysis, patients with TSE had higher pre-therapy PSA, PSA velocity, and ALP (p

99mTc-MIBI (MIBI) imaging is able to exclude malignancy of hypofunctioning thyroid nodules (TNs) with high probability but false positive results are frequent due to low specificity. Therefore, pre-test selection of appropriate TNs is crucial. For image evaluation visual and semiquantitative methods (Washout index, WOInd) are used. Aim of this study was to evaluate the diagnostic performance of MIBI imaging in hypofunctioning TNs with indeterminate fine-needle aspiration cytology results in a multicentric European setting. Patients with hypofunctioning TNs, EU-TIRADS 4 or 5, Bethesda III/IV and MIBI imaging were included. For visual evaluation the intensity of MIBI uptake in the TN was compared to normal thyroid tissue. 358 patients with 365 TNs (n = 68 malignant) were included. Planar imaging (SPECT) showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 96% (94%), 21% (22%), 22% (15%), 96% (96%), and 35% (32%). The WOInd (38.9% of all cases, optimal cutoff: −19%) showed a sens 100% (spec 89%, PPV 82%, NPV 100%, ACC 93%). For hypofunctioning TNs at intermediate or high risk with indeterminate cytology, a MIBI negative result on visual evaluation is an effective tool to rule-out thyroid malignancy. The semi-quantitative method could considerably improve overall diagnostic performance of MIBI imaging.

Purpose To evaluate the distribution of metastatic lymph nodes (LN) detected on 68Ga-PSMA-positron emission tomography/computed tomography (PET/CT) in treatment-naive prostate cancer (PC) patients and to analyze the LN coverage rates of the pelvic fields defined in the GETUG trial and RTOG guidelines and a pelvic field extending superiorly from the L4/L5 interspace. Materials and methods 68Ga-PSMA-PET/CT images obtained at diagnosis of 138 PC patients were retrospectively analyzed. The number and locations of 68Ga-PSMA-positive LNs were co-registered with one single-planning CT. The numbers, locations, and sizes of LNs located outside the three pelvic volumes were investigated for the entire cohort and for patients with LN metastasis in the pelvic area only. Results A total of 441 PSMA-PET-positive LN metastases were identified. The most frequent metastatic LNs were internal iliac LNs (25.2%). Para-aortic and presacral LNs outside the three pelvic fields were present in 20 (14.5%) and 22 patients (15.9%), respectively. The LN coverage rates according to the GETUG trial, the RTOG guidelines, and the pelvic field extending superiorly from L4/L5 were 44.2%, 52.2%, and 71, respectively, in the entire cohort and 51.7%, 61 and 83.1%, respectively, in patients with only pelvic LN metastasis. The number of metastatic LNs was a predictive factor for LNs located outside the three pelvic fields. Conclusions Extending the cranial margin of the pelvic field from L5/S1 to L4/L5 increases the accuracy of pelvic field irradiation in approximately 20% of patients, highlighting the importance of proximal common iliac irradiation, particularly in patients with multiple LN metastasis.

Prostate cancer (Pca) is the most common cancer and the second leading cause of death among men. Although conventional bone scans and abdominal CT are preferred in most of the guidelines and clinical trials, PET/CT has already started to become the inevitable part of Pca management because of its higher sensitivity and specificity. Radiotracers used for PET imaging show different molecular aspects of the disease process. Although Ga-prostate-specific membrane antigen offers the highest sensitivity and specificity, other PET radiotracers such as F-FDG and Ga-DOTATATE still have a role in patients with prostate-specific membrane antigen-negative diseases such as Pca with neuroendocrine differentiation. In this pictorial essay, we have presented a series of patients with metastatic Pca who had PET images with different radiotracers and discussed the clinical role of this imaging modality in patient management.

Medullary thyroid cancer (MTC) arises from neuroendocrine C cells of the thyroid. There is no single diagnostic imaging method that can reveal all MTC recurrences or metastases. 68Ga-DOTATATE is an alternative PET radiotracer that showed acceptable efficacy in the detection of MTC. In this study, we aimed to reveal the clinical efficacy and impact of this radiotracer on the management of patients with MTC. The 68Ga-DOTATATE PET-CT records of 38 patients with confirmed MTC were included in the study. The demographic data, clinical indication for the scan, previous therapies, and tumor marker levels were recorded. The site and SUVmax of the lesions were also noted. A consensus was reached on the additional value of 68Ga-DOTATATE PET-CT, and sites with discordant results on conventional imaging (CI). Finally, changes in management after the scan were evaluated. 68Ga-DOTATATE PET-CT outperformed CI in 14/38 (37%) patients. In these 14 patients, metastatic lymph nodes were detected in 8, bone metastases in 4, and both bone and lymph nodes metastases in 2 patients. In 16/38 (42%) patients, 68Ga-DOTATATE PET-CT performed equally well as CI. In 5/38 (13%) patients, CI outperformed PET-CT. Most of the patients (4/5) in this group had hepatic metastases. 68Ga-DOTATATE PET-CT positivity was also correlated with tumor marker expression [median calcitonin; PET-positive: 743 ± 5439 vs PET-negative: 45 ± 17 (p:0.012), median CEA; PET-positive: 41 ± 162 vs PET-negative: 2.6 ± 1.4 (p:0.015)]. 68Ga-DOTATATE PET-CT changed the clinical management of 13/38 (34%) patients. The information provided by PET-CT resulted in neck surgery in 5/13 patients, external radiotherapy in 3/13 and both in one patient. Four of these thirteen patients were found to be eligible for peptide receptor radionuclide therapy. 68 Ga-DOTATATE is an essential part of the work-up for patients with MTC. This modality outperformed CI in 14/38 (37%) patients and changed the clinical management in 13/38 (34%) patients. Prospective randomized studies with image-guided therapy decisions are needed to further reveal the impact of PET imaging in patients with MTC.

OBJECTIVE In patients with non-Hodgkin lymphoma (NHL), we investigated F FDG PET/computed tomography (CT) parameters, clinical findings, laboratory parameters, and bone marrow involvement (BMI) status for predictive methods in progression-free survival (PFS) and overall survival (OS), and whether F FDG PET/CT could take the place of bone marrow biopsy (BMB). METHODS The performance of F FDG PET/CT (BMPET) was evaluated. The prognostic value of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), stage, international prognostic index (IPI) score, IPI risk, lactate dehydrogenase (LDH), B2 microglobulin, Ki67 proliferation index, and the presence of BMI was evaluated for OS and PFS. Kaplan-Meier curves were drawn for each designated cutoff value, and 5-year PFS and 7-year OS were evaluated using log-rank analysis. RESULTS The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of BMPET and BMB to identify BMI were 69, 100, 86.1, 80, 100%, and 81.6, 100, 92.5, 89, 100%, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of BMPET in patients with Ki67- proliferation index >25% were all 100%. BMPET, IPI risk, MTV, and LDH were found to be independent prognostic predictors for PFS, whereas BMPET, SUVmax, and MTV for OS. Five-year PFS analysis estimated as follows: BMPET (+) = 22%, BMPET (-) = 80%, LDH ≤ 437 (U/L) = 86%, LDH > 437 (U/L) = 51%, MTV ≤ 56 (cm) = 87%, MTV > 56 (cm) = 49%, low IPI risk = 87%, intermediate IPI risk = 69%, high IPI risk = 25%. Seven-year OS analysis was found as: SUVmax ≤ 17.6 = 80%, SUVmax > 17.6 = 48%, MTV ≤ 56 (cm) = 84.4%, MTV > 56 (cm) = 45.8%, BMPET (-) = 72.5%, BMPET (+) = 42%. CONCLUSION In the Ki-67 proliferation index > 25% group, F FDG PET/CT was able to differentiate BMI independently from NHL subgroups. We recommend using this method with large patient groups. MTV and BMPET were independent prognostic indicators for OS and PFS and may help to determine high-risk patients.

During the last few years, especially since the American Thyroid Association guidelines was released in 2015, there has been an intense debate on the management of thyroid cancer with particular emphasis on the use of radioactive iodine for diagnostic and therapeutic purposes. The Society of Nuclear Medicine and Molecular Imaging (SNMMI) and The European Association of Nuclear Medicine (EANM) have just published joint practice guidelines on the nuclear medicine evaluation and therapy of differentiated thyroid cancer (DTC) [1]. Recently, the European Thyroid Association (ETA) also released the 2022 ETA Consensus Statement: “What are the indications for post-surgical radioiodine therapy in differentiated thyroid cancer?” [2]. In addition, not long ago, a German position paper from surgery and nuclear medicine was published in reaction to the ETA Consensus Statement with a very different perspective, similar to the newly published SNMMI/EANM guideline [3]. Overall, despite the use of the widely accepted risk-adapted therapy, its interpretation and relative approaches to DTC management, and in particular to the clinical use of radioactive iodine, still differ significantly in European countries [4].

In the original publication [...]

Purpose: There is a need to evaluate the treatment response in patients who have undergone radioiodine treatment (RIT) for differentiated thyroid cancer. Our study aimed to show thyroid hormone withdrawal (THW) effects on quality of life and psychological symptoms in female patients with low-risk, well-differentiated papillary thyroid cancer. Methods: We applied the short form-36 (SF-36) and Symptom Checklist-90-R (SCL-90-R) questionnaires to the patients in the euthyroid state who have referred a median of 9 months (6-13 months) after RIT to perform a diagnostic whole-body scan (dWBS) and to evaluate stimulated Tg. We applied the same questionnaire again when thyroid-stimulating hormone (TSH) was > 30 μIU/mL 4 weeks after THW (hypothyroid state). We evaluated the changes in questionnaire scores using the paired-samples t-test or the Wilcoxon signed-rank test. Results: Our study included 52 patients (median age 48 years, range 23-65 years). There was a statistically significant worsening in anxiety, psychosis, additional items, and general symptom index symptoms with the SCL-90-R questionnaire, physical functioning, role limitation due to physical health, energy/fatigue, emotional well-being, social function, general health, and health change with the SF-36 questionnaire. Conclusions: THW worsened the patients' psychological symptoms and quality of life. Thyrotropin alfa is an alternative to reduce side effects, but it can be costly and difficult to obtain in developing countries. In order to reduce the side effects of hypothyroidism and avoid the high cost, treatment response assessment can be done only in selected patient groups.

A 60-year-old woman with recurrent urinary tract infection who had several operations for colorectal carcinoma underwent Tc-DMSA renal scintigraphy which showed an unexpected accumulation of radiotracer in the colon. When symptoms were reviewed, we noticed that she was suffering from pneumaturia and fecaluria which raised the suspicion of enterovesical fistula. Rectal contrast-enhanced computer tomography of pelvis demonstrated enterovesical and enterovaginal fistulas. Colonic radioactivity was considered to be related to retrograde peristalsis of Tc-DMSA from bladder activity via enterovesical fistula. In patients with pelvic surgeries and radiotherapy, radioactivity in the colon should raise the suspicion of enterovesical fistula.

Objective: There is a need to evaluate the treatment response in patients who have undergone radioiodine treatment (RIT) for differentiated thyroid cancerDiagnostic tests that are used for this purpose include radioiodine whole body scan (sWBS) and serum thyroglobulin (Tg) measurement which are most accurate during thyroid-stimulating hormone (TSH) stimulation. However temporary discontinuation of thyroid hormone therapy to increase TSH (withdrawal) may be associated with the morbidity of hypothyroidism The aim of our study was to show the effects of thyroid hormone withdrawal (THW), on quality of life and psychological symptoms in female patients with low-risk, well-differentiated papillary thyroid cancer. Methods: We applied the short form-36 (SF-36) and Symptom Checklist-90-R (SCL-90-R) questionnaires to the patients in the euthyroid state who were referred a median of 9 months (6-13 months) after RIT, to perform a dWBS and to evaluate stimulated Tg. We applied the same questionnaire again when thyroid-stimulating hormone (TSH) was > 30 μIU/mL 4 weeks after THW (hypothyroid state). We evaluated the changes in questionnaire scores using the paired-samples t test or the Wilcoxon signed rank test. Results: Our study included 52 patients (median age 48 years, range 23-65 years) with differentiated cancer. Forthy –two (%) of these patients received 3700 MBq I-131 wheras 7 (%) patients received 1850 MBq. . Ablation success based on the dWBS only was 96.2%, based on Tg only was 98% and based on thyroglobulin antibodies (TgAb) only was 88.5%. There was statistically significant worsening in anxiety, psychosis, additional items and general symptom index symptoms with the SCL-90-R questionnaire, and physical functioning, role limitation due to physical health, energy/fatigue, emotional well-being, social function, general health and health change with the SF-36 questionnaire. Conclusions: THW worsened the patients’ psychological symptoms and quality of life. Our findings show that stimulated Tg and the dWBS may have side effects that outweigh benefits in patients with low-risk differentiated thyroid cancer without TgAb interference and access to ultrasonography.

A 47-year-old woman with atypical pituitary adenoma was referred to the neurosurgery department due to recent back pain. She had multiple transsphenoidal surgery, stereotactic body radiation, and 177Lu-DOTATATE therapy. Her spinal MRI showed multiple spinal masses. The patient underwent 68Ga-DOTATATE PET/CT to confirm the metastatic spread of the disease. PET/CT images showed increased uptake at the local recurrent tumor site and spinal metastases confirmed by biopsy to pituitary carcinoma. Our case presents the role of 68Ga-DOTATATE PET/CT in patients with pituitary carcinoma.

Cancer is the major burden of disease worldwide. The folate receptor, as a specific tumor target, is over-expressed in many types of cancer including ovarian carcinomas, breast, colon, renal, and lung tumors. Nuclear medicine hybrid imaging modalities, such as SPECT/CT, provide both metabolic and anatomic information. Therefore, specific contrast agents are essentially needed. Liposomes are favorable systems with many advantages. The aim of this study was to formulate liposomal imaging agents for molecular tumor imaging by SPECT or SPECT/CT and evaluate their efficacy. Nanosized, polyethyleneglycolated, folate-conjugated and unmodified, diethylenetriaminepentaacetic acid-phosphatidylethanolamine containing, neutral and positively charged liposomes were formulated and characterized by mean particle size, zeta potential, and quantitative determination of the phospholipids in the liposomes. The binding of the synthetized imaging agents to 4T1 breast tumor cells was evaluated by fluorescence microscopy and radioactivity counting. Folate-conjugated neutral and positively charged liposomes were found to be effective as tumor imaging agents exhibiting an almost 3-fold increased uptake and brighter fluorescence microscopy images than unmodified ones in in vitro experiments using 4T1 breast tumor cells. These results could be considered as an important step towards the development of folate-specific agents for tumor imaging by SPECT and SPECT/CT.

Well planned re-surgery is critical for recurrent/persistent thyroid cancer (TC). We aimed to investigate the clinical outcome of radioguided-occult lesion localization (ROLL) guided surgery in patients with recurrent/persistent TC.This study includes 29 patients [F/M: 22/7, median age 43 ± 12 years (18-58)] with a diagnosis of TC (22 papillary, 2 follicular and 5 medullary). Before surgery, all patients underwent ultrasonography (USG) guided mapping and intra-lesional radioactivity injection. Surgery was performed based on the excision of radioactivity injected lesions by a gamma probe and non-injected tumor foci via USG-neck map. Researchers determined surgical success by post-operative tumor markers and neck-USG.Among 29 patients, 60 metastatic lesions were identified by USG [median size 10 ± 6.3 mm (range 5-30)]. Neck-USG performed after surgery provided no evidence of disease (NED) in %97 (28/29) of TC patients. In the follow-up, stimulated thyroglobulin (Tg) levels were less than 1 ng/ml in 79%(19/24) of DTC patients and suppressed Tg 0.2 ng/ml was noted in 92% (22/24).In patients with DTC with an incomplete structural response, we dramatically changed the American Thyroid Association (ATA) response category and achieved an excellent response in 92% (22/24) of patients. Among patients with MTC, 5/5 patients had normal USG and calcitonin levels were reduced by 60-80% in 4/5 and 80% in1/5 patients.In this study we have shown that, ROLL-guided surgery yielded NED rate of %97 (28/29) and increased excellent response rates according to ATA guidelines. Further studies with larger patient groups and longer follow-up should be performed to confirm the efficacy of this surgery.

Neck dissection (ND), whether therapeutic or elective, is an essential component of the treatment of head and neck squamous cell carcinoma (HNSCC). Due to altered anatomy and fibrosis caused by initial treatments, surgeons face challenges during salvage ND. A combination of Technetium-99 m and indocyanine green (ICG) previously used in the sentinel lymph node (SLN) biopsy for oral cavity cancers, may be useful in different types of neck surgeries. We aimed to show the additional advantage of this combination in detecting HNSCC and thyroid cancer recurrences, as well as individual lymphatic drainage in elective ND. We retrospectively reviewed medical records of patients, underwent neck surgery guided with ICG and Tc-99 m, in Hacettepe University Hospital between June 2018 and December 2020. In a total of 28 patients, intraoperative gamma probes were paired with near infrared (NIR) cameras. Patients are divided into two groups: neck surgery with recurrent occult lesion localization (NS- ROLL) (n: 14) and ND with SLN screening (ND-SLNS) (n: 14). Among all 14 patients in NS-ROLL group, recurrent diseases, hidden behind tissues were 100% successfully localized. In ND-SLNS group, 238 lymph nodes were harvested, metastasis rate was 31.3% (10/32) in sentinel nodes. SLNS revealed 100% accuracy in detecting metastasis in clinically N0 neck (10/238). Contralateral lymphatic drainage was observed in three patients (lateral-sided oral cavity SCC). In two patients (floor of mouth), three sentinel nodes were detected by NIR only. The use of ICG-radiotracer provides additional value in disease removal for both primary and recurrent tumors of the head and neck.

Introduction Postoperative complications following thoracic procedures are a major cause of morbidity and mortality. Alveolar air leaks and/or bronchopleural fistulas are associated with increased risk of infection, prolonged chest tube, and hospital stay duration and therefore generate economical concern for health care providers. A variety of surgical sealants or adhesives have been introduced to overcome this complication. Since intraoperative BioGlue® application can also cause an inflammatory reaction and mimic tumor recurrence on FDG PET-CT, in the present study we aimed to investigate its potential role in false-positive PET-CT results in patients operated for NSCLC. Materials and methods Data of six patients who underwent resection for primary NSCLC at our institution (Department of Thoracic Surgery, Hacettepe University Medical Faculty) between January 2015 and December 2018 and had false positivity, due to BioGlue® application, at the bronchial stump in follow-up FDG PET-CT were retrospectively analyzed from a prospectively collected database. Result One of the 6 patients was female and 5 were male. The mean age was 68 years (range, 56-79 years). The average time interval between operation and postoperative FDG-PET imaging was 4.3 months (range, 4-6 months). Follow-up FDG-PET imaging SUVmax values ranged between 3.0 and 9.0 (median: 5.33). All patients have been evaluated by FDG-PET scan following the detection of soft tissue densities at the surgical site suspicious for recurrence at their follow-up chest CT scans. Four patients underwent a bronchoscopic examination, bronchial stumps were examined and multiple biopsies were taken from suspicious nodules or tissues and sent for pathologic examination. Histopathological results revealed inflammation which is compatible with foreign body granuloma, without any suspicion for malignancy, in all cases. Two patients were solely followed-up and subsequent FDG-PET imaging after 3 months revealed complete resolution of FDG uptake. Conclusions To avoid unnecessary biopsies or surgical procedures, the possibility of false-positive results due to surgical adhesive product use should be taken into account while interpreting follow-up FDG-PET imaging results and the operative reports should be written in detail, describing which surgical materials used and their exact application sites.

Defining the extent of disease spread with imaging modalities is crucial for therapeutic decision-making and definition of treatment. This study aimed to investigate whether clinical parameters and nomograms predict prostate-specific membrane antigen (PSMA)-positive lymph nodes in treatment-naïve nonmetastatic prostate cancer (PC) patients.The clinical data of 443 PC patients (83.3% high-risk and 16.7% intermediate-risk) were retrospectively analyzed. Receiver operating characteristic (ROC) curves with areas under the curve (AUC) were generated to evaluate the accuracy of clinical parameters (prostate-specific antigen [PSA], T stage, Gleason score [GS], International Society of Urological Pathology [ISUP] grade) and nomograms (Roach formula [RF], Yale formula [YF], and a new formula [NF]) in predicting lymph node metastasis. The AUCs of the various parameters and clinical nomograms were compared using ROC and precision-recall (PR) curves.A total of 288 lymph node metastases were identified in 121 patients (27.3%) usingThe clinical T stage, PSA, GS, and ISUP grade are independent predictors of PSMA-positive lymph nodes. The RF and YF can be used to identify patients who can benefit from

Positron emission tomography-computed tomography (PET-CT) performed with new radiopharmaceuticals has revolutionized the imaging area in prostate cancer (Pca). 68Ga/18F-labeled prostate-specific membrane antigen (PSMA) has been the most promising radiotracer for staging and restaging of Pca. PSMA-based imaging outperformed conventional imaging (CI) in restaging and has a high clinical impact in patient management. Recently introduced 99mTc-labeled-PSMA compounds provide intraoperative guidance, which improved surgical outcomes of salvage surgical therapy. This chapter mainly focuses on PSMA-based imaging and discuss the potential benefits and limitations.

Purpose Molecular imaging with 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI, MIBI) has been used in the assessment of thyroid nodules (TNs) for more than two decades. Many studies showed that MIBI imaging is a suitable tool to rule-out malignancy when negative. However, relatively low specificity and accuracy have been described, thus, limiting its acceptance in clinical practice. Additionally, different technologies, protocols, and interpretation criteria are adopted accounting for heterogeneous data reported in the literature. Therefore, the present study was undertaken to assess the clinical use and methodology of MIBI imaging in patients with nodular thyroid disease in Europe. Methods A questionnaire was sent to 12 European centers of Nuclear Medicine. The questionnaire encompassed ultrasound (US) and fine-needle aspiration cytology (FNAC) procedures and their evaluation as well scintigraphy imaging indications, technical procedures, and interpretation criteria of MIBI imaging. Results The survey showed a good agreement of different centers in approaching TNs by TSH measurement, US evaluation and 99mTc-pertechnetate thyroid scintigraphy. MIBI imaging is mainly used to assess TNs with inconclusive/indeterminate cytological findings and selection of target nodule(s) for FNAC in patients with multi-nodular goiter. Technical procedures adopted in different centers are globally comparable and the recorded differences are unlikely to impact clinical results. However, as the main result of the present study, substantial differences were found in interpretation criteria adopted in different centers. Conclusions Our survey supports the urgent need of standardized interpretation criteria of thyroid MIBI imaging in order to improve its diagnostic performance and make results comparable in clinical practice.

Tumor sink effect (TSE) has been defined as; decreased uptake in healthy tissue with increased tumor sequestration of the radiopharmaceuticals. It enables us to give high tumoral radiation doses while resulting in lower absorbed radiation to critical organs. However, the factors which influence this effect are yet to be defined. In this study, we have investigated the predictive factors of the tumor sink effect in a group of patients who receivedWe have retrospectively analyzed the pre-therapyBased on the post-therapy scans, TSE was seen in 17/65 (26.2%) patients. In univariate analysis, patients with TSE had higher pre-therapy PSA, PSA velocity, and ALP (p 0.0001). In relation to PET parameters, patients with TSE had higherThe tumor sink effect was seen in 26.2% of patients.

Gallium-68-labeled prostate-specific membrane antigen (Ga-PSMA) positron emission tomography (PET)/computed tomography (CT) is a valuable diagnostic tool for the detection of bone metastases in patients with prostate cancer (PCa). However, bone scintigraphy (BS) with technetium-labeled diphosphonates is cheap and widely available for the same patient population. PSMA PET comes with a cost, and financial constraints in the present economic environment may require its more selective use. In this study, we aimed to compare the diagnostic performance of BS with Ga-PSMA PET/CT for the detection of bone metastases in patients with PCa and correlate the results with various clinical and biochemical variables. Ninety-five patients who underwent Ga-PSMA PET/CT and BS within 3 months for newly diagnosed or recurrent PCa were extracted from our database. Lesion, region and patient-based analyses were performed. Clinical and imaging follow-up was used as the reference test. Results were compared with tumor grade, serum prostate-specific antigen (PSA), and alkaline phosphatase (ALP) values. On the patient-based analysis, 75% (42/56) and 98.2% (55/56) of the patients with bone metastases were correctly diagnosed by BS and Ga-PSMA PET, respectively. In 26/95 patients with equivocal lesions on BS, Ga-PSMA PET correctly reclassified skeletal involvement in 11 and excluded metastases in 15 patients BS missed bone metastases in 3 patients. The true-positive rate of BS in patients with serum ALP ≥ 120U/L and PSA ≥ 50 ng/ml was 95.8% and 87.5 respectively. Ga-PSMA is superior to BS for the evaluation of metastatic disease in patients with PCa. However, BS can also detect bone metastases in patients with PCa with a minimum sensitivity of 75%. Biochemical data are helpful to select patients with a high pretest probability who should undergo BS first as a part of the initial workup from an economic point of view. Due to its higher cost, Ga-PSMA PET should be performed in a selective group of patients when BS results are inconclusive or metastasis-directed therapy is planned.

Medullary thyroid cancer (MTC) arises from neuroendocrine C cells of the thyroid. There is no single diagnostic imaging method that can reveal all MTC recurrences or metastases.The

NSCLC is the most common type of lung cancer. However, non-specific contrast agents, radiopharmaceuticals, and treatment methods are insufficient in early diagnosis and eradication of all tumor tissue. Therefore, the formulation of a novel, targeted, specific theranostic agents possess critical importance. In our previous study, paclitaxel and vinorelbine encapsulating, Tc-99m radiolabeled, folate targeted, nanosized liposomes were formulated and found promising due to characterization properties, high cellular uptake, and cytotoxicity. In this study, in vivo therapeutic and diagnostic efficacy of liposomal formulations were tested by biodistribution study, evaluation of tumor growth inhibition, and histopathologic examination after in vitro assays on LLC1 cells. Both actively and passively targeted liposomal formulations exhibited high cellular uptake, and co-drug encapsulating liposomes showed a greater cytotoxicity profiles than free drug combination in LLC1 cells. By the results of biodistribution studies performed in NSCLC tumor-bearing C57BL/6 mice, the uptake of radiolabeled, actively folate targeted, co-drug encapsulating liposomal formulation was found to be higher in tumor tissue when compared to non-actively targeted one. Also, more effective treatment was achieved by using folate-targeted, co-drug encapsulating liposomal formulation when compared to free drugs combination according to changes in tumor size of mice. Furthermore, liposomal formulations showed lower toxicity compared to free drug combinations in the toxicity study considering body weight. Moreover, according to the histopathological study, folate targeted, co-drug encapsulating liposomes not only inhibited the tumor growth effectively but also restricted the lung metastasis entirely.

Introduction Despite the increasing accuracy of imaging modalities, the rate of benign renal tumors misclassified as malignant before surgery still non-negligible. Tc-99m sestamibi was demonstrated to be a possible reliable agent in discriminating oncocytoma from renal cell carcinoma (RCC). We aimed to study the efficacy of Tc-99m MIBI tumor scintigraphy in evaluating clinical T1 renal masses. Methods and Materials Between July 2017 and March 2019, patients with clinical T1 renal mass underwent preoperative Tc-99m sestamibi tumor scintigraphy. Tc-99m sestamibi tumor scintigraphy findings were correlated with the postoperative pathology results. Results A total of 90 renal masses were included in the study. Male to female ratio was 67/23. The mean age and tumor size were 55.5 ± 11.4 years and 4 ± 1.4 cm, respectively. In pathological evaluation, 20% (18/90) of masses were reported as benign (10 oncocytomas, 4 angiomyolipomas (AML), 2 chronic sclerosis, 1 fibroma and 1 hydatid cyst). While Tc-99m sestamibi uptake was positive in all oncocytomas; 6 patients with chronic sclerosis, fibroma, hydatid cyst and angiomyolipoma pathologies had no uptake. Except for 5 chromophobe cell RCC and 3 oncocytic papillary RCC masses, malignant lesions had no uptake. In predicting benign pathology, Tc-99m sestamibi tumor scintigraphy had positive and negative predictive value of 60% and 91.3%, respectively. The mean Tc-99m 2-methoxy isobutyl isonitrile lesion/normal renal parenchyma ratio of benign and malignant lesions was 0.6 and 0.37, respectively. A relative uptake of 0.49 was an acceptable cutoff point to discriminate oncocytomas from all other pathologies. Conclusion Tc-99m sestamibi tumor scintigraphy has a beneficial role in the assessment of clinical T1 renal mass. Masses with negative uptake harbor high probability of being malignant. While evaluating masses with positive uptake, it should be kept in mind that some malignant pathologies may demonstrate similar results.

Background Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. These tumors are rare and only make bone metastases at a rate of 5%. Case summary A 31-year-old male with a GIST presented with solitary bone metastasis at the right iliac bone. We performed stereotactic ablative radiotherapy (SABR) and achieved excellent local control. Herein, our case is presented, and a short review of the literature is carried out. Conclusion SABR should be considered as a treatment option in GIST with bone metastasis.

68Ga-PSMA Positron Emission Tomography/Computerized Tomography (PET/CT) has shown promising results for the detection of recurrent prostate cancer (RPCa). However, the diagnostic value of this method is yet to be validated. The aim of this study was to determine the influence of clinical and biochemical variables on the detection rate of 68Ga-PSMA PET/CT in patients with RPCa. This is a prospective study of 121 patients who underwent 68Ga-PSMA-PET/CT and conventional imaging (CI) for RPCa. Detection rates were analyzed and correlated with various clinical and biochemical variables such as Gleason score GS), androgen deprivation therapy (ADT), trigger PSA (tPSA), PSA doubling-time (PSAdt) and PSA velocity (PSAv). 68Ga-PSMA-PET/CT showed at least one focus of pathological 68Ga-PSMA uptake in 92/121 (76%) of patients. Nodal metastases (in 47% of patients) were the most common site of recurrent disease followed by bones (36%) and prostate (32%). Out of 121 patients, 57 (47%) had only positive findings on PSMA scan verified by biopsy or follow-up. The majority of these lesion were located in the lymph nodes (31/57, 54,5%), which were below the detection limit of CT. Univariate analysis showed higher detection rate of PET/CT with increasing tPSA, PSAv and short PSAdt. Best cutoff for tPSA, PSAv and PSAdt was 0.5 ng/ml, 2.25 ng/ml/year and 8.65 months, respectively. The detection rate of PSMA-PET/CT was higher in patients with high grade tumors (GS > 7, 23.7% vs 76.3%) and in patients who were on ADT during of PSMA scan (76.3% vs 96%). In multiple logistic regression analysis, PSAdt and concurrent ADT were identified as predictors of positive 68Ga-PSMA-PET/CT. 68Ga-PSMA-PET/CT is useful for re-staging patients with RPCa and has improved performance compared with CI for disease detection. Detection rates are improved in patients on ADT and with short PSAdt.

Resumen Paciente de 54 anos de edad con cancer de prostata al que se realizo estudio PET/TC con 68Ga-PSMA que mostro afectacion linfatica y metastasis oseas. Despues de 2 ciclos de tratamiento con 177Lu-PSMA, una nueva PET/TC mostro disminucion de la captacion en los ganglios linfaticos y las lesiones oseas, pero aparecieron nuevas lesiones compatibles con progresion de la enfermedad o efecto llamarada. La revision de las imagenes de 177Lu-PSMA mostro que las nuevas lesiones de la segunda PET/TC correspondian a lesiones metastasicas que captaban mas que en la primera PET/TC y que posteriormente presentaron buena respuesta. El paciente recibio ciclos adicionales de tratamiento con 177Lu-PSMA con regresion de la enfermedad, alcanzando niveles de PSA de 0,06 ng/ml. La evaluacion de la respuesta de los nuevos agentes «teragnosticos» precisa realizar una revision no solo de las imagenes diagnosticas de la PET/TC sino tambien de las imagenes posterapia y los datos de laboratorio.

Glucagonomas are rare types of pancreatic neuroendocrine tumors. They may present with a clinical entity called glucagonoma syndrome, which includes necrolytic migratory erythema as a skin component. Here we present a 26-year-old woman experiencing ongoing skin lesions, excessive weight loss, and nausea. She was diagnosed with metastatic glucagonoma. Her 68Ga-DOTATATE PET/CT showed increased uptake at the primary pancreatic lesion and hepatic metastases. She received 2 cycles of peptide receptor radionuclide therapy and had a partial response with a near-complete regression of her skin lesions.

Thyroid stimulating hormone receptor (TSHR) plays a pivotal role in thyroid hormone metabolism. It is a major controller of thyroid cell function and growth. Mutations in TSHR may lead to several thyroid diseases, most commonly hyperthyroidism. Although its genetic and epigenetic alterations do not directly lead to carcinogenesis, it has a crucial role in tumor growth, which is initiated by several oncogenes. This article will provide a brief review of TSHR and related diseases.Tiroid stimulan hormon reseptörü (TSHR) tiroid hormon metabolizmasında merkezi bir rol oynar. Tiroid hücrelerinin fonksiyonlarının ve büyümesinin kontrolünde yardımcıdır. TSHR mutasyonları bir dizi tiroid hastalığına, en çok hipertiroidizme neden olmaktadır. Her ne kadar bu reseptörün genetik ve epigenetik değişiklikleri direkt olarak karsinogeneze yol açmasa da, farklı onkogenler tarafından başlatılmış tümörün büyümesinde ciddi bir rol oynar. Bu makalede TSHR ve ilişkili hastalıklar özetlenmektedir.

Background Non-Hodgkin’s lymphomas arising from the tissues other than primary lymphatic organs are named primary extranodal lymphoma. Most of the studies evaluated metabolic tumor parameters in different organs and histopathologic variants of this disease generally for treatment response. We aimed to evaluate the prognostic value of metabolic tumor parameters derived from initial FDG-PET/CT in patients with a medley of primary extranodal lymphoma in this study. Patients and methods There were 67 patients with primary extranodal lymphoma for whom FDG-PET/CT was requested for primary staging. Quantitative PET/CT parameters: maximum standardized uptake value (SUVmax), average standardized uptake value (SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were used to estimate disease-free survival and overall survival. Results SUVmean, MTV and TLG were found statistically significant after multivariate analysis. SUVmean remained significant after ROC curve analysis. Sensitivity and specificity were calculated as 88% and 64%, respectively, when the cut-off value of SUVmean was chosen as 5.15. After the investigation of primary presentation sites and histo-pathological variants according to recurrence, there is no difference amongst the variants. Primary site of extranodal lymphomas however, is statistically important (p = 0.014). Testis and central nervous system lymphomas have higher recurrence rate (62.5%, 73%, respectively). Conclusions High SUVmean, MTV and TLG values obtained from primary staging FDG-PET/CT are potential risk factors for both disease-free survival and overall survival in primary extranodal lymphoma. SUVmean is the most significant one amongst them for estimating recurrence/metastasis.

Theranostics labeled with Y-90 or Lu-177 are highly efficient therapeutic approaches for the systemic treatment of various cancers including neuroendocrine tumors and prostate cancer. Peptide receptor radionuclide therapy (PRRT) has been used for many years for metastatic or inoperable neuroendocrine tumors. However, renal and hematopoietic toxicities are the major limitations for this therapeutic approach. Kidneys have been considered as the "critical organ" because of the predominant glomerular filtration, tubular reabsorption by the proximal tubules, and interstitial retention of the tracers. Severe nephrotoxity, which has been classified as grade 4-5 based on the "Common Terminology Criteria on Adverse Events," was reported in the range from 0%-14%. There are several risk factors for renal toxicity; patient-related risk factors include older age, preexisting renal disease, hypertension, diabetes mellitus, previous nephrotoxic chemotherapy, metastatic lesions close to renal parenchyma, and single kidney. There are also treatment-related issues, such as choice of radionuclide, cumulative radiation dose to kidneys, renal radiation dose per cycle, activity administered, number of cycles, and time interval between cycles. In the literature, nephrotoxicity caused by PRRT was documented using different criteria and renal function tests, from serum creatinine level to more accurate and sophisticated methods. Generally, serum creatinine level was used as a measure of kidney function. Glomerular filtration rate (GFR) estimation based on serum creatinine was preferred by several authors. Most commonly used formulas for estimation of GFR are "Modifications of Diet in Renal Disease" (MDRD) equation and "Cockcroft-Gault" formulas. However, more precise methods than creatinine or creatinine clearance are recommended to assess renal function, such as GFR measurements using Tc-99m-diethylenetriaminepentaacetic acid (DTPA), Cr-51-ethylenediaminetetraacetic acid (EDTA), or measurement of Tc-99m-MAG3 clearance, particularly in patients with preexisting risk factors for long-term nephrotoxicity. Proximal tubular reabsorption and interstitial retention of tracers result in excessive renal irradiation. Coinfusion of positively charged amino acids, such as l-lysine and l-arginine, is recommended to decrease the renal retention of the tracers by inhibiting the proximal tubular reabsorption. Furthermore, nephrotoxicity may be reduced by dose fractionation. Patient-specific dosimetric studies showed that renal biological effective dose of

Aim To evaluate the use of intraoperative gamma probe survey (IGPS) and frozen section (FS) in the surgical treatment of parathyroid adenoma (PA) in children. Patients and methods Children operated for PA between 2000 and 2015 were evaluated for age, sex, clinical features, presenting symptoms, diagnostic methods and results of surgical treatment retrospectively. Results Seven patients operated for PA were included in the study. The mean age of the patients was 14.58years (11–17years) and male to female ratio was 4:3. Presenting symptoms were non-specific such as fatigue, weakness and abdominal pain ( n =4). Six patients (85.8%) had adenoma of single parathyroid gland whereas remaining patient has involvement of two glands (14.2%). Localizations of adenomas were left inferior ( n =3, 42.8%), right inferior ( n =2, 28.3%), right superior ( n =1, 14.2%), left superior ( n =1, 14.2%) and intrathymic ( n =1, 14.2%). In case with involvement of more than one gland, adenomas were localized at right superior/left inferior glands. The mean longest diameter of the adenomas were 14.8mm (4–23mm) and all of the cases were underwent USG and Tc-99m sestamibi scan. During surgical excision, FS were used in 5 cases, and 4 cases had IGPS after preoperative radioactive substance injection. In one patient, injection was performed directly into the adenoma and 3 patients had systemic injection. Patient who had injection directly into the involved gland had positive gamma counts in the adjacent tissues because of local spread of radioactive substance and diagnosis was also confirmed with FS. In two of the cases, adenoma excision was performed without FS with only IGPS. None of the patients had preoperative and postoperative complications. Conclusion PA is rare in children and appropriate gland excision can be obtained also by the help of IGPS after injection of radioactive substance, and frozen section examination as well as intraoperative parathormone (PTH) screening. IGPS is a helpful tool to define the target tissue during surgery in order to avoid extensive dissection. Since direct injection of involved gland may cause accumulation of radioactivity in the adjacent tissues, surgeons must be aware of advantages and disadvantages of different radiolabeling techniques.

Secondary involvement of the adrenal gland with non-Hodgkin’s lymphoma has been reported to occur in up to 25% of patients during the course of the disease. A 45-year-old man presented with a several month history of nausea, fatigue and weight loss. His medical history was unremarkable. Abdominal computed tomography (CT) was performed and showed bilateral adrenal massive masses measuring 10x7.5 cm on the left and 4.8x4 cm on the right. He developed adrenal insufficiency in the follow-up period. The patient was started on replacement dose of prednisolone. A positron emission tomography-CT scan was acquired for further staging of the disease and showed intense fluorodeoxyglucose accumulation in both adrenal glands, additionally a slight fluorodeoxyglucose accumulation was observed in the ileocecal site. He did not accept adrenal biopsy or surgery. Histopathological examination of the ileocecal site revealed diffuse large B-cell lymphoma. He was administered rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. Bilateral adrenal lymphoma is a rare entity when compared with the incidence of adenoma and adrenal metastases of other cancers. Adrenal insufficiency may be the primary symptom of presentation, especially with bilateral involvement as in bilateral adrenal lymphoma.