[64Cu]Copper chloride PET-CT: a comparative evaluation of fasting and non-fasting states in patients of prostate carcinoma.

Altered copper metabolism in cancer has been linked to increased intracellular copper uptake mediated by human copper transporter 1, with [64Cu]Cu2+ as a potential biomarker for cancer theranostics. [64Cu]CuCl2 PET-CT though explored in various malignancies, a lack of standardized protocol exists, particularly regarding fasting status before imaging. This analysis aimed to evaluate the requirement of fasting for [64Cu]CuCl2 PET-CT along with temporal changes in physiological organ uptake in delayed scans. A total of 26 patients of prostate carcinoma who underwent [64Cu]CuCl2 PET-CT imaging were divided into two groups: (1) nonfasting (n = 12) and (2) fasting (n = 14). The nonfasting group received an average dose of 350 MBq, while the fasting group received 300 MBq of [64Cu]CuCl2, and PET-CT images acquired approximately 60-90 min (1 h image) and 3-3.5 h (delayed image) after intravenous injection of the tracer. An experienced nuclear medicine physician evaluated the images for qualitative assessment between the groups. Multiple spherical regions of interest were placed at sites of physiological organ uptake of the tracer and over the diseased lesions to measure the mean SUVmax. No significant difference was observed in the qualitative assessment of the images between the two groups (except for a slight predilection towards more hepatic tracer retention observed in the fasting group), including in the delayed images. The liver demonstrated the highest tracer uptake in all patients, with a mean SUVmax of 21.5 in the fasting group and 19.7 in the nonfasting group, showing no significant difference (P = 0.32). The kidneys, intestines, and salivary glands also showed similar trends of tracer uptake in both groups. The study illustrated that the fasting or nonfasting status did not affect image quality or semiquantitative measurements significantly in physiological organs and diseased lesions in patients with carcinoma prostate.

Incidental Detection of Second Primary Thyroid Malignancy in Patients of Metastatic Castration-Resistant Prostate Carcinoma: Documentation on 68 Ga-PSMA-11 and 64 CuCl 2 PET/CT.

ABSTRACT: Second primary tumors are being increasingly detected owing to and in proportion to the use of advanced imaging modalities including PET/CT. Patients suffering from prostate cancer have been reported to have increased second primary cancers of gastrointestinal tract, urinary bladder, and thyroid. We herein describe incidental detection of thyroid carcinoma, in 2 patients of mCRPC (metastatic castration-resistant prostate carcinoma) undergoing preradioligand therapy workup, on 68 Ga-prostate-specific membrane antigen PET/CT initially, subsequently also observed on multitracer PET/CT ( 64 CuCl 2 and 18 F-FDG). Thus, the potential of PET/CT for early in vivo second primary detection in mCRPC setting is illustrated in the aforementioned 2 patients.

Familial MEN1 Syndrome Diagnosed on Functional Imaging: A Case Report with Clinical and Genetic Correlation.

Multiple endocrine neoplasia, type 1 (MEN1) syndrome is an autosomal dominant disease characterized by tumors involving parathyroid, pituitary, and pancreas. The diagnosis is mostly clinical and by the presence of MEN1 gene mutation. We present a case with initial presentation of neuroendocrine tumor of pancreas whose ancillary findings on 68 Ga-DOTATATE positron emission tomography-computed tomography helped in raising suspicion of MEN1, which was confirmed on genetic testing and family history. We emphasize the importance of using gestalt approach in such cases to avoid misdiagnosis or delay. Additionally, we describe the clinical profile of affected family members with their MEN1 gene mutation status, highlighting the gestalt approach again to uncover the unknowns.

Exploratory analysis of 64 CuCl 2 PET-CT imaging in carcinoma prostate and its comparison with 68 Ga-PSMA-11 and 18 F-FDG PET-CT.

AIM: Exploratory analysis of 64 CuCl 2 PET-CT imaging in patients of carcinoma prostate and its head-to-head comparison with 68 Ga-PSMA-11 and 18 F-FDG PET-CT. METHODS: In this prospective study, 50 patients of biopsy-proven carcinoma prostate belonging to the entire spectrum of disease were evaluated, out of which 21 patients were for initial staging and 29 were for restaging/response evaluation. Both 64 CuCl 2 (early and delayed) and 68 Ga-PSMA-11 PET-CT were undertaken in all patients and 18 F-FDG PET-CT was done in patients whenever possible. All scans were done within a period of 2 weeks, without any interim therapeutic intervention. 64 CuCl 2 PET-CT was acquired at 1 and 3 h. We evaluated the physiological uptake of 64 CuCl 2 , correlated the uptake in primary with disease parameters like Gleason score and serum PSA levels, and compared the detection rates for primary and metastatic disease with 68 Ga-PSMA-11 and 18 F-FDG PET-CT. RESULTS: The detection rates of primary disease were same for both 64 CuCl 2 and 68 Ga-PSMA-11 PET-CT and both agents performed similarly in detecting extra-prostatic disease. There was no statistically significant correlation observed between the uptake of 64 CuCl 2 in the primary lesion with disease parameters. With regard to the evaluation of metastatic disease, the detection rate of 64 CuCl 2 PET-CT was 86% for lymph nodes, 77.3% for skeletal metastases and 80.6% for soft tissue metastases while 68 Ga-PSMA-11 PET-CT performed better with detection rates were 98%, 99% and 85.4%, respectively. In 17 patients where 18 F-FDG PET-CT was available, 64 CuCl 2 PET-CT detected more metastatic disease than 18 F-FDG PET-CT. CONCLUSION: 64 CuCl 2 PET-CT did not show any additional advantage over 68 Ga-PSMA-11 PET-CT in evaluation of local disease or for the assessment of metastatic disease. When compared to 68 Ga-PSMA-11 PET-CT, the absence of urinary bladder and ureteric activity allows better contrast for evaluating local disease, but it does not translate into increased disease detection.

Assessment of Pulmonary Metastasis in Differentiated Thyroid Carcinoma: Value of HRCT Correlation with Functional Imaging.

Pulmonary metastases in thyroid carcinoma demonstrates varying imaging characteristics and disease biology and the outcome. The valuable complimentary role of high-resolution CT (HRCT) in conjunction with functional imaging such as radioiodine scan has been discussed and illustrated in this review along with the varied clinical and imaging presentations of lung metastases from differentiated thyroid cancer (DTC). A multi-modality patient-specific diagnostic approach and awareness about the atypical presentations helps in early identification as well as effective management of these patients, and especially in certain situations that could need multi-disciplinary management. While HRCT of the lungs as an added tool provides detailed visualization of the lung parenchyma, in the era of hybrid imaging, the routine adoption of SPECT-CT in patients with pulmonary metastases (in diagnostic or post-treatment settings) could provide equivalent or even incremental information from further management viewpoint.

Correlation of Lesional Uptake Parameters and Ratios with miPSMA Score and Estimating Normal Physiologic Concentration: An Exploratory Analysis in Metastatic Castration-Resistant Prostatic Carcinoma Patients with 68Ga-PSMA-11 PET/CT.

The use of prostate-specific membrane antigen (PSMA)-based PET/CT has grown rapidly in recent years. This study estimated lesional uptake, normal physiologic concentrations, and temporal variation on delayed PET/CT of 68Ga-PSMA-11 across different molecular imaging PSMA (miPSMA) expression scores in patients with metastatic castration-resistant prostatic carcinoma. Methods: We retrospectively studied 50 patients who were evaluated for 177Lu-PSMA-targeted radioligand therapy and underwent 68Ga-PSMA-11 PET/CT to determine disease status. Their mean age was 67.5 ± 8 y (52-84 y), and their average serum prostate-specific antigen level was 401 ± 1,353 ng/mL (0.098-9,235.13 ng/mL) at the time of scanning. They underwent standard 68Ga-PSMA-11 PET/CT an average of 65 min after injection (60-90 min). Tumors (n = 50) were correlated with miPSMA expression score and uptake. Physiologic tracer distribution was estimated by placing a volume of interest 1 cm in diameter for smaller organs (submandibular, parotid, lacrimal, and tubarial glands; renal cortices; blood pool; and bowel) and 3 cm for larger organs (liver and spleen). SUVmax and SUVmean were estimated for each region. Tumor-to-spleen (T/S), tumor-to-liver (T/L), and tumor-to-parotid (T/P) ratios were calculated for each lesion. For 16 patients who underwent a delayed scan an average of 135 min after injection (120-150 min), additional analysis evaluated the effect of the delay. Results: Uptake was maximal in renal cortices, followed by salivary glands, bowel, spleen, liver, lacrimal glands, and blood pool. SUVmax averaged 37.7 ± 22.1 for renal cortices, 15.4 ± 7.3 for submandibular glands, 14.4 ± 7.1 for parotid glands, 9.4 ± 4.9 for spleen, 6.2 ± 3.7 for lacrimal glands, 5.9 ± 2.3 for liver, 5.3 ± 1.41 for tubarial glands, 13.8 ± 7.6 for bowel, and 2.4 ± 1.9 for blood pool. SUVmax averaged 10.33 ± 3.27 (6.46-17) for miPSMA expression score 2 and 38.21 ± 25.9 (7.68-119.08) for score 3. T/S and T/P ratios averaged 1.21 ± 0.44 (0.48-2.04) and 0.6 ± 0.18 (0.39-0.87), respectively, for score 2 and 5.05 ± 4.46 (1.25-20.89) and 3.15 ± 2.09 (1.06-9.45), respectively, for score 3. SUVmax for score 3 lesions averaged 18.85, which increased significantly to 26.24 on delayed imaging (P = 0.0001). However, T/L, T/S, and T/P ratios did not significantly change. Temporal variation in normal organs showed SUVmax to increase significantly on delayed scans for salivary (submandibular and parotid) and lacrimal glands and renal cortices, whereas SUVmean increased significantly for spleen; liver; and parotid, tubarial, and lacrimal glands and insignificantly for other organs. Conclusion: These data form a basis for a proposed consensus on standard reference ranges for quantitative 68Ga-PSMA-11 PET/CT. The temporal variations should be kept in mind for delayed acquisitions; T/S, T/L, and T/P ratios might serve as better markers for such scenarios.

Standardized uptake values and ratios on 68Ga-DOTATATE PET-computed tomography for normal organs and malignant lesions and their correlation with Krenning score in patients with metastatic neuroendocrine tumors.

The aim was to estimate the physiological standardized uptake values (SUVs) on Ga-DOTATATE PET-computed tomography (CT) in normal organs and metastatic tumor lesions (both standard and delayed), and correlating the uptake values and ratios with Krenning Scores (K-score) in patients with metastatic/advanced neuroendocrine tumors (NETs) undergoing PET-CT studies for their management work-up. A total of 32 patients of metastatic NET with 95 discrete tumor lesions were included in this analysis. These patients underwent standard whole-body PET-CT following injection of 2-3 mCi (74-111 MBq) of Ga-DOTATATE at 1-1.5 h. The normal physiological SUVmean of the liver and spleen and SUVmax and SUVmean of tumor lesions were estimated by an in-built automated procedure. These patients also underwent a delayed scan (2.5-3 h) and the same parameters were obtained for the delayed study. The tumorous lesions were further classified on the basis of K-score, and this was correlated with the mean SUVmax on both early and delayed scans. SUVmean ratios (tumor-to-liver and tumor-to-spleen) were also calculated for both time-points and correlated with individual K-scores. In lesions with K-score 4, the mean SUVmax was 32.5 in early and 30.5 in delayed scan, for lesions with K-score of 3 and 2, the mean SUVmax were 17.3, 20, and 9.3, 9.2, respectively, while in K-score 1 (n = 1), the delayed mean SUVmax was found to be more than early mean SUVmax (3.2 to 2.3). Statistical significance was evaluated by paired t test, and the changes in SUVmax was found to be statistically insignificant (P > 0.05) in all 3 K-scores. The paired t test was also performed between early and delayed tumor/liver and tumor/spleen mean SUVmean ratios, and no significant changes were observed across all K scores. The mean SUVmean values of the liver in the standard 1-h scan and delayed scans were 8.05 (range: 3-15) and 8.17 (range: 3.2-16), while for spleen, the values were 18 (range: 8.4-36.7) and 20 (range: 10-38.6), respectively. Statistically significant changes were observed in delayed spleen SUVmean values compared to the early scan (P < 0.05), while for liver SUVmean, the difference was not significant. Thus, in the present study, the SUVmax and SUVmean (range and mean values) for normal liver and spleen, and malignant NET lesions, and tumor-to-liver and tumor-to-spleen SUVmean ratios of different K-scores were generated. As could be theoretically expected in receptor-based PET-CT, there was no significant change in the delayed scan compared to the standard 1-1.5 h values.

PET/Computed Tomography in Pulmonary and Thoracic Inflammatory Diseases (Including Cardiac Sarcoidosis): The Current Role and Future Promises.

18F-fluorodeoxyglucose PET/computed tomography (CT) can play a valuable adjunct role in initial and post-treatment assessment of thoracic and pulmonary inflammatory disorders and is particularly helpful when the conventional biomarkers and anatomical imaging are non-contributory or inconclusive. PET/CT can potentially help in chronic obstructive pulmonary disease (COPD). Quantitative regional parameters of inflammation, perfusion, and ventilation estimated by PET/CT have the potential to cause a paradigm shift in the management of COPD. This article highlights the role of PET/CT in thoracic inflammatory disorders, with an overview of newer aspects such as quantification, disease phenotyping, new tracers, and new techniques.

Interpreting discordance on dual-tracer positron emission tomography-computed tomography in the setting of metastatic neuroendocrine tumor: Detection of metachronous triple-negative breast carcinoma.

Second primary malignancies (SPMs) are known to be associated with neuroendocrine tumors (NETs). The association necessitates a careful assessment of the dual-tracer positron emission tomography-computed tomography (PET-CT) imaging findings to identify these malignancies earlier. Such early diagnosis can provide incremental benefit for screening these SPMs apart from their known applications in the management of NETs. A case of incidentally detected metachronous triple-negative breast carcinoma on dual-tracer PET-CT imaging is presented using 18fluoro-2-deoxy-D-glucose (FDG) and 68Ga-DOTATATE that showed a high uptake on FDG but no uptake on somatostatin receptor-based imaging.

18F-fluorodeoxyglucose positron emission tomography/computed tomography in carcinoma of unknown primary: A subgroup-specific analysis based on clinical presentation.

The aim of this study was to explore the clinical efficacy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in tumor detection in patients with proven or suspected carcinoma of unknown primary origin (CUP) and making a subgroup-specific analysis. This was a retrospective, cross-sectional survey of patients with CUP syndrome who were referred for 18F-FDG PET-CT studies over a 2-year period. FDG-PET-CT scans were performed in compliance with the standard whole-body protocol, i.e., at least 6 h of fasting and were carried out with injected FDG radioactivity dose between 259 MBq and 370 MBq. The time from FDG injection to PET data acquisition was between 60 and 90 min. PET/CT scanning was acquired from the skull base to the upper third of the thighs. Nonenhanced, low-dose attenuation correction CT (110/70 kV/mAs) was performed for all patients. Twenty-one patients of clinically designated with CUP (male:female = 7:14; age range: 42-70 years; mean age: 57.95 years) fulfilling the inclusion criteria were enrolled in this analysis. The patients were subdivided into two groups: A - Those with histopathological proof (n = 12); B - Those with clinical/tumor markers/radiological suspicion of malignancy (n = 9). Among the first group, the sites of metastases in decreasing order of frequency were lymph nodes (n = 9/20; 75%), brain (n = 2; 16.67%), and liver (n = 1; 8.33%). In group B, six patients (66.7%) presented with hypodense/enhancing lesions in the brain and three (33.3%) had altered marrow signal intensity of spine. Overall, hypermetabolic lesions on FDG-PET/CT indicating the primary tumor sites were identified in 14 patients (66.7%). Twelve out of 14 primary sites were subsequently proven by histopathology, whereas two patients with biopsy-proven metastatic lesions in brain, with suspicious primary site in lung had been corroborated by FDG-PET/CT revealing multiple other metastatic sites, were not biopsied and were subsequently enrolled for palliative chemotherapy. When the results were examined individually in each of the Group A and Group B, the primary tumor detection rate was 58.3% and 77.7%, respectively. The identified primary tumor sites were lung 9/14 (64.4%), uterus/cervi 2/14 (14.3%), breast 1/14 (7.1%), esophagus 1/14 (7.1%), and aryepiglottic fold 1/14 (7.1%). In conclusion, FDG-PET/CT is not only helpful in histologically proven cases of CUP (irrespective of the metastatic sites), this modality also demonstrates high tumor detection rate in patients with clinical/radiological suspicion of malignancy. Being a whole body technique, it can additionally aid in disease staging in these patients which could be potentially helpful in their clinical management.

Resistant functioning and/or progressive symptomatic metastatic gastroenteropancreatic neuroendocrine tumors: efficacy of 177Lu-DOTATATE peptide receptor radionuclide therapy in this setting.

BACKGROUND AND AIMS: Functioning and symptomatic disease resistant to conventional therapies constitutes a subset amongst neuroendocrine tumors (NETs) that are commonly considered for peptide receptor radionuclide therapy (PRRT). The aim of this study was to evaluate the efficacy of Lu-DOTATATE PRRT in this group with objective assessment criteria. MATERIALS AND METHODS: A total of 46 patients with refractory or progressive symptomatic GEP-NETs (previously treated at various stages with long-acting octreotide, chemotherapy, multikinase inhibitors, etc.) who had undergone treatment with PRRT were retrospectively analyzed. These patients were evaluated for response on three scales: clinical, biochemical parameters (tumor marker levels), and imaging (functional molecular and contrast enhanced anatomic). They were classified as complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD) on each scale. Furthermore, the patients were classified as (a) those who gained benefit from PRRT and (b) those who were nonresponders using predefined criteria. RESULTS: Ninety-one percent of the patient population had liver metastases, with a mean serum chromograninA level of 3307 U/ml, consistent with high volume tumor burden and refractory symptoms. Clinical symptomatic response on an analogue scale showed 54% CR, 35% PR, and 6% SD, whereas 4% showed worsening of symptoms. Biochemically, 17% CR, 28% PR, and 28% SD were observed, whereas 12% showed PD. On evaluation by imaging (PERCIST and RECIST 1.1 criteria), we observed 4% CR, 39% PR, and 36% SD, whereas 19% showed PD. The clinical scale showed the highest overall benefit of 95.6% in the population studied. CONCLUSION: The data support the evidence that PRRT could be potentially beneficial in resistant, refractory, and progressive symptomatic groups of GEP-NETs with functional disease burden. The use of a multidimensional response evaluation should be adopted (rather than only anatomical-functional imaging) and needs to be considered while managing this subset of patients.

Thyroglobulin "Nonsecretor" Metastatic Poorly Differentiated Thyroid Carcinoma with Noniodine Concentrating Disease and Aggressive Clinical Course: A Clinical Case Series.

Poorly differentiated thyroid carcinomas (PDTC) are a subgroup of thyroid cancers with aggressive behavior and worse prognosis compared to the well DTC. Limited diagnostic tools and therapeutic options exist for such cases, and the appropriate management algorithm continues to evolve in this subgroup. They pose difficulty in clinical management due to their behavioral heterogeneity and increased occurrence of aggressive clinical behavior underlining the need for management individualization. In the present communication, a case series of three clinically challenging cases of PDTC (with low serum thyroglobulin (Tg) and iodine nonavidity) are presented with a discourse on their management intrigues, unresolved issues and the requirement of a distinctive management protocol. A small fraction of PDTCs may show low serum Tg values, with the questionable significance of its role for the assessment and monitoring of disease burden in this group of patients. Given uncommon occurrence, limited and variable literature data, management guidelines for "nonsecretor" PDTC needs to be more clearly defined based on scientific evidence. The present clinical case series of PDTC with low serum thyroglobulin in the context of noniodine concentrating metastatic disease and aggressive clinical course ("nonsecretor" status) was noteworthy from this viewpoint.

Non-18F-2-Fluoro-2-Deoxy-d-Glucose PET/Computed Tomography in Gynecologic Oncology: An Overview of Current Status and Future Potential.

The current status and future potential targets of non-18F-2-fluoro-2-deoxy-d-glucose (FDG) PET/computed tomography (CT) in 3 major gynecologic malignancies are discussed. Estrogen receptor-based 16alpha-18F-fluoro-17beta-estradiol (18F-FES) PET/CT has been investigated in (a) Uterine malignancies (both endometrial and myometrial pathologies) and (b) ovarian carcinoma. For uterine tumors, FDG/FES standardized uptake value and/or uptake ratio showed a positive correlation with malignant transformation (ie, endometrial carcinoma and uterine sarcoma) and higher malignant grades, whereas higher 18F-FES uptake was documented in benign pathologies (ie, endometrial hyperplasia and leiomyoma). For epithelial ovarian carcinomas, 18F-FES PET/CT can predict the response to antiestrogen therapy in platinum-resistant cases.