Axumin (18F-Fluciclovine) PET imaging in men exhibiting no clinically significant cancer on initial negative biopsy of PI-RADS 4 and 5 regions of interest.

PURPOSE: The objective of the study was to determine whether Axumin (18F-Fluciclovine) PET/MRI informs the decision to perform an early repeat biopsy of PI-RADS 4/5 region of interest (ROI) exhibiting no clinically significant prostate cancer (csPCa) on initial biopsy. METHODS: This prospective study enrolled men with at least one PI-RADS 4/5 ROI on multi-parametric MRI and no csPCa on prior biopsy defined as Gleason grade group (GGG) > 1. All men underwent an Axumin PET/MRI and only-persistent PI-RADS > 2 ROI were advised to undergo a repeat biopsy. A PET cancer suspicion score (PETCSS) was internally developed to stratify PET avid lesions according to their suspicion of harboring csPCa. The sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of the PETCSS for predicting csPCa were assessed. Relative risk was calculated to analyze the association of baseline variables with csPCa on repeat biopsy. RESULTS: Thirty-eight ROI on 36 enrolled men were analyzed. Fourteen (36.8%) were downgraded to PI-RADS 1/2 and were not subjected to repeat biopsy. Thirteen (92.9%) of these downgraded scans also exhibited low-risk PETCSS. Overall, 18/22 (81.2%) subjects underwent a repeat per protocol biopsy. Of the 20 ROI subjected to repeat biopsy, eight (40%) were found to harbour csPCa. The sensitivity, specificity, PPV and NPV of the PETCSS were 50, 50, 40, and 60%, respectively. No predictor of csPCa was found in the risk analysis. CONCLUSION: Our pilot study showed that both MRI and PET sequences have limited performance for identifying those persistently suspicious PI-RADS 4/5 ROI that are found to harbor csPCa on repeat biopsy.

The ability of an arginine to tryptophan substitution in Saccharomyces cerevisiae tRNA nucleotidyltransferase to alleviate a temperature-sensitive phenotype suggests a role for motif C in active site organization.

We report that the temperature-sensitive (ts) phenotype in Saccharomyces cerevisiae associated with a variant tRNA nucleotidyltransferase containing an amino acid substitution at position 189 results from a reduced ability to incorporate AMP and CMP into tRNAs. We show that this defect can be compensated for by a second-site suppressor converting residue arginine 64 to tryptophan. The R64W substitution does not alter the structure or thermal stability of the enzyme dramatically but restores catalytic activity in vitro and suppresses the ts phenotype in vivo. R64 is found in motif A known to be involved in catalysis and nucleotide triphosphate binding while E189 lies within motif C previously thought only to connect the head and neck domains of the protein. Although mutagenesis experiments indicate that residues R64 and E189 do not interact directly, our data suggest a critical role for residue E189 in enzyme structure and function. Both R64 and E189 may contribute to the organization of the catalytic domain of the enzyme. These results, along with overexpression and deletion analyses, show that the ts phenotype of cca1-E189F does not arise from thermal instability of the variant tRNA nucleotidyltransferase but instead from the inability of a partially active enzyme to support growth only at higher temperatures.

18F-Fluciclovine Uptake in Thymoma Demonstrated on PET/MRI.

ABSTRACT: A 68-year-old man with a history of prostate cancer post-primary treatment presented with rising prostate-specific antigen levels and was referred for 18F-fluciclovine PET/MRI to localize recurrent disease. PET/MRI revealed a solitary focus of uptake in a soft tissue nodule in the anterior mediastinum, which was resected and found to be a type B2 thymoma. 18F-fluciclovine uptake is mediated by amino acid transporters, primarily alanine-serine-cysteine transporter 2 and l-type amino acid transporter 1, previously demonstrated to be expressed on thymic carcinomas. This case highlights the possibility of overexpression of amino acid transporters in thymomas as well, rarely described before.

Correlation of 68Ga-DOTATATE uptake on PET/CT with pathologic features of cellular proliferation in neuroendocrine neoplasms.

OBJECTIVE: 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) is a useful tool for diagnosing and staging neuroendocrine neoplasms (NEN). Unlike other PET tracers like FDG, the meaningfulness and use of standardized uptake values (SUVs) of 68Ga-DOTATATE is not well-established. This study aimed to determine if a correlation exists between intensity of 68Ga-DOTATATE uptake and markers of cellular proliferation. METHODS: This retrospective study included 79 patients with positive 68Ga-DOTATATE PET/CT and Ki-67 and/or mitotic index (MI) available on pathology report. SUVmax of the most intense lesion and the most intense organ-matched lesion were determined. Demographics and pathology results for Ki-67 and MI were collected from the electronic medical record. Correlations and trends for correlations of SUVmax to Ki-67 and MI were performed using Kruskal-Wallis and Cuzick trend tests. RESULTS: A trend for an association between SUVmax and Ki-67 grade was found; median SUVmax of Ki-67 < 3%, 3-20%, and > 20% was 35.2, 31.8, and 12.8 (p = 0.077), respectively. There was also a trend between SUVmax and Ki-67 categories in organ-matched lesions (p = 0.08). The median organ-matched SUVmax of MI < 2, 2-20, and > 20 lesions was 34.2, 18, and 21.7, respectively, (Cuzick trend test p = 0.066). The median SUVmax for small bowel, pancreatic, and other primary locations was 27.6, 46.9, and 9.3 (p < 0.01), respectively. CONCLUSIONS: The association between 68Ga-DOTATATE SUVmax, histologic grade, and primary site of NEN demonstrates its potential use for prognostication, or potentially as a surrogate for histologic grading when biopsy is not possible.

PET/CT for Lymphoma Post-therapy Response Assessment in Other Lymphomas, Response Assessment for Autologous Stem Cell Transplant, and Lymphoma Follow-up.

FDG-PET/CT is an established first-line diagnostic imaging tool used in the staging of most lymphomas and for post-therapy response assessment in Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL). Many of the subtypes of lymphoid neoplasms classified by the World Health Organization demonstrate significant FDG-avidity or uptake; however, many guidelines and Lugano classification do not recommend the use of FDG-PET/CT in assessing response to therapy for these non-HL, non-DLBCL subtypes as a first-line diagnostic tool. This article reviews the role of FDG-PET/CT in the evaluation of the other most common "FDG-avid" lymphomas than HL and DLBCL, the role of FDG-PET/CT before autologous stem cell transplant, and for post-treatment follow-up. Follicular lymphoma is most commonly FDG-avid with a wide range of uptake that generally correlates with the histologic grade, a major determinant of aggressiveness and prognosis. FDG-PET/CT is more sensitive and specific than CT for detecting residual disease post therapy for both aggressive and indolent follicular lymphoma. Post-treatment FDG-PET/CT for follicular lymphoma has significant prognostic value, that is, better predicts progression-free and overall survival than does conventional post-treatment assessment with CT. FDG-PET/CT is useful in the staging of mantle cell lymphoma, a very aggressive, incurable subtype of lymphoma; however, data show mixed results on the benefits of FDG-PET/CT over conventional CT assessment in post-therapy response evaluation. Peripheral T-cell lymphomas, a rare aggressive group of T-cell lymphomas, are often FDG-avid. Post-therapy FDG-PET/CT results have major prognostic value and therapeutic implications in many subtypes of peripheral T-cell lymphomas. Post-treatment FDG-PET/CT is superior to conventional CT for determining chemosensitivity of lymphoma, and therefore is better able to predict which patients will have a greater benefit or outcome with autologous stem cell transplant. There are mixed data on the value of FDG-PET/CT for surveillance after treatment because of high reported false-positive rates and accuracy that depends on the duration or timing of surveillance and the subtype of lymphoma.

Interrupted 131I Procedures for Patients With Differentiated Thyroid Cancer: Comparing Thyroxine Withdrawal With Recombinant Thyrotropin Preparation Techniques.

OBJECTIVE: In patients with differentiated thyroid carcinoma scheduled to receive doses of I for diagnostic or therapeutic purposes, we compared patients prepared with thyroid hormone withdrawal (THW) versus recombinant human thyroid stimulating hormone (rh-TSH) to evaluate the incidence of cancelled procedures because of inadequate thyroid stimulation. METHODS: Thyroid cancer patients after thyroidectomy who were scheduled for diagnostic or therapeutic I procedures between January 2012 and June 2015 were retrospectively reviewed. Patients were divided based on preparation modality (THW vs rh-TSH), and the incidence of cancelled procedures was compared. RESULTS: Charts from 761 patients were reviewed, 292 THW and 569 rh-TSH. A total of 10 patients (3.4%) in the THW group had cancelled procedures because of insufficient thyroid stimulation (TSH < 20 mU/L). If a TSH threshold of 30 mU/L were used, 57 patients (17.1%) would have been cancelled. Comparing the groups with chi-squared analysis for both TSH thresholds yielded significantly more cancellations in the THW group (P < 0.001). CONCLUSIONS: Our study has shown that THW in preparation for I procedures leads to significantly more cancellations because of insufficient thyroid stimulation as compared with rh-TSH, which led to no cancellations. The added cost and inconvenience to this cancer population should therefore be considered when selecting a preparation modality. LEVEL OF EVIDENCE: Retrospective cohort-Level III.

Nuclear Imaging of a Cardiac Paraganglioma.

We report a case of a cardiac paraganglioma in the right atrioventricular groove in which the use of different nuclear medicine studies aided in the diagnosis.

Vertebral Uptake of Tc-99m Macroaggregated Albumin (MAA) with SPECT/CT Occurring in Superior Vena Cava Obstruction.

A 67-year-old male presented with dyspnea for which lung scintigraphy was ordered to rule out pulmonary embolus. Planar images demonstrated abnormal midline uptake of Tc-99m macroaggregated albumin, which SPECT/CT localized to several thoracic vertebrae. Thoracic vertebral uptake on perfusion lung scintigraphy was previously described on planar imaging. Radionuclide venography and contrast-enhanced CT subsequently demonstrated superior vena cava (SVC) obstruction with collateralization through the azygous/hemiazygous system and vertebral venous plexus. SPECT/CT differentiated residual esophageal/tracheal ventilation activity, a clinically insignificant finding, from vertebral uptake indicative of SVC obstruction, a potentially life-threatening condition.

18F-FDG PET/CT Imaging of Bilateral Renal Metastasis of Breast Adenoid Cystic Carcinoma.

We report the case of a 65-year-old woman with a history of adenoid cystic carcinoma (ACC) of the breast. Fifteen years after mastectomy, the patient underwent a right upper lobectomy for a lung mass, and biopsy indicated ACC metastasis. Ten years after lobectomy, an F-FDG PET/CT was performed for restaging to rule out further metastases. We observed intense FDG uptake in enlarged polylobulated kidneys, which was biopsy proven as ACC metastasis.

Value of thyroid incidentalomas on positron emission tomographic scans among thyroidectomy patients.

OBJECTIVES: To evaluate the preoperative predictive value of a positive positron emission tomographic (PET) scan with respect to malignancy in future thyroidectomy candidates, particularly when the fine-needle aspiration biopsy (FNAB) results in indeterminate findings, and to establish the efficiency with which this can be incorporated as a preoperative marker and potentially contribute to a standardized scoring system for thyroid nodule patients. METHODS: This retrospective study examined 1048 thyroidectomy patients, of whom 45 underwent PET with computed tomography for unrelated reasons, among which 13 results were focally positive. The final pathology was evaluated and compared to this result to determine the correlation. RESULTS: All patients with positive PET results were shown postthyroidectomy to have a thyroid malignancy (13 of 13), corresponding to a positive predictive value of 100%. There was no correlation between a negative PET scan and malignancy, however. When integrating the PET scan criteria in the McGill Scoring System, 4 of these 13 were shifted into a high chance of malignancy group, allowing a more accurate assessment of their risk than they might have previously received. CONCLUSION: In comparison with previous data, our results indicate a strong relationship between a positive PET scan and malignancy. If available and used in conjunction with the other preoperative diagnostic tools (outlined by the McGill Thyroid Nodule Scoring System), this test can hold significant merit in determining a therapeutic strategy, particularly in the face of an indeterminate FNAB.

McGill Thyroid Nodule Score (MTNS): "rating the risk," a novel predictive scheme for cancer risk determination.

OBJECTIVE: There are presently a great number of publications pertaining to the clinical risk factors associated with thyroid cancer. These studies deal mostly with a single feature from either patient demographics, physical examination, laboratory values, imaging, or cytology. We sought to create a novel scoring system that integrates the diagnostic indices of each of these clinical features for carcinoma. METHODS: A retrospective analysis of 1047 consecutive thyroidectomy patients was performed. Each patient was assigned a cancer risk score according to a newly devised 22-variable scoring scheme termed the McGill Thyroid Nodule Score (MTNS). The MTNS was developed by a multidisciplinary team of endocrinologists, thyroid surgeons, and pathologists using already established evidence-based risk factors for thyroid cancer. RESULTS: The exact incidence of malignancy was calculated for each MTNS score based on final pathology. The incidence for scores of 1 to 3 was 27%, of 4 to 7 was 32%, of 8 was 39%, of 9 to 11 was 63%, of 12 to 13 was 88%, and of 14 to 18 was 93%. All (130 of 130) patients with a score ≥ 19 had carcinoma. A score ≤ 8 correlated with a 32% (115 of 357) risk of thyroid cancer, whereas a score > 8 implied an 86% (417 of 487) risk. CONCLUSION: Our data suggest that a combined scoring system, the MTNS, can serve as an accurate predictor of the risk for thyroid cancer in a specific thyroid nodule. This will help physicians better formulate management decisions accordingly.

Preoperative serum thyroglobulin as an adjunct to fine-needle aspiration in predicting well-differentiated thyroid cancer.

BACKGROUND/PURPOSE: when fine-needle aspiration biopsy (FNAB) of a thyroid nodule yields indeterminate pathology, management decisions become complex, and other preoperative predictors of thyroid cancer must be employed to assess the risk of malignancy. Although thyroglobulin (Tg) is currently accepted as the serum marker of choice in the detection of well-differentiated thyroid cancer (WDTC) recurrence, its preoperative role in the workup of a thyroid nodule remains controversial. The purpose of this study was to evaluate the potential role for Tg as a preoperative indicator of primary WDTC, specifically in patients with indeterminate FNAB. METHODS: this was a retrospective review of 861 consecutive thyroidectomy patients; 297 patients had indeterminate FNAB, of which 68 had serum levels of Tg measured prior to surgery. The predictive value of various threshold levels of preoperative Tg for WDTC was evaluated. Patients with nonindeterminate FNAB or final pathology containing medullary carcinoma, anaplastic carcinoma, or lymphoma were excluded. RESULTS: eighty-one percent (25 of 31) of patients with both indeterminate FNAB and preoperative Tg ≥ 75 microg/L had well-differentiated cancer on final pathology compared to 58% (172 of 297) of patients with indeterminate cytology alone (p = .014, RR = 1.4). In addition, mean preoperative Tg levels were found to be significantly higher in patients with WDTC compared to those with benign pathology (223 vs 53 microg/L, p = .007). DISCUSSION/CONCLUSION: our results imply that elevated preoperative serum Tg levels may be predictive of WDTC. This marker may be useful as an aid when making management decisions in patients with indeterminate cytology.