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Controversial Issues in Thyroid Cancer Management.
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Controversial Issues in Thyroid Cancer Management.

J Nucl Med. 2018 Apr 13;:

Authors: Tuttle RM

Abstract
The lack of prospective randomized clinical trials for most management topics in differentiated thyroid cancer force us to make management recommendations based on retrospective observational data which is often incomplete, subject to selection bias, and conflicting. Therefore, it is not surprising that many aspects of thyroid cancer management remain controversial and not well defined. This review will examine the controversies surrounding three important topics in thyroid cancer management: (1) the option of thyroid lobectomy as initial therapy for thyroid cancer, (2) the proper use of preoperative neck imaging to optimize the completeness of the initial surgical procedure, and (3) the selective use RAI therapy as remnant ablation, adjuvant treatment or treatment of known persistent/recurrent disease. As thyroid cancer management moves toward a much more risk adapted approach to personalized management recommendations, clinicians and patients must balance the risks and benefits of the potential management options to arrive at a management plan that is optimized based on both patient preferences/values and the philosophy/experience of the local disease management team.

PMID: 29653980 [PubMed - as supplied by publisher]




FDG-PET response of skeletal (bone marrow and bone) involvement after induction chemotherapy in pediatric Hodgkin lymphoma - Are specific response criteria required?
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FDG-PET response of skeletal (bone marrow and bone) involvement after induction chemotherapy in pediatric Hodgkin lymphoma - Are specific response criteria required?

J Nucl Med. 2018 Apr 13;:

Authors: Georgi TW, Kluge R, Kurch L, Chavdarova L, Hasenclever D, Stoevesandt D, Pelz T, Landman-Parker J, Wallace H, Karlen J, Fernandez-Teijeiro A, Cepelova M, Fossa A, Balwierz W, Attarbaschi A, Ammann RA, Pears J, Hraskova A, Uyttebroeck A, Beishuizen A, Dieckmann K, Leblanc T, Daw S, Baumann J, Körholz D, Sabri O, Mauz-Körholz C

Abstract
Purpose: This study focused on skeletal involvement in FDG-PET (PET) in Hodgkin lymphoma (HL). We aimed at a systematic evaluation of the different types of skeletal involvement and their PET response after two cycles of chemotherapy (PET-2), to answer the question whether the current PET response criterion for skeletal involvement is suitable. A secondary objective was to observe the influence of initial uptake intensity and metabolic tumor volume (MTV) of skeletal lesions on the PET-2 response. Methods: Initial PET scans (PET-0) of 1068 pediatric HL patients from the EuroNet-PHL-C1 (C1) trial were evaluated by central review for skeletal involvement. Three types of skeletal lesions were distinguished: skeletal lesions detected only in PET (PETonly), bone marrow (BM) lesions confirmed by MRI or BM biopsy and bone lesions. Uptake intensity (measured as qPET value) and MTV were calculated for each skeletal lesion. All PET-2 scans were assessed for residual tumor activity. The rates of complete metabolic response in PET-2 of skeletal and nodal involvement were compared. Results: 139/1068 (13%) C1 patients showed skeletal involvement (44/139 PETonly patients, 32/139 BM patients and 63/139 bone patients). 101/139 (73%) patients became PET-2 negative in the skeleton while lymph node involvement was PET-2 negative in 94/139 (68%) patients. Highest skeletal PET-2 negative rate was seen in 42/44 (95%) PETonly patients, followed by 22/32 (69%) BM patients and 37/63 (59%) bone patients. Skeletal lesions who became PET-2 negative showed lower median values for initial qPET (2.74) and MTV (2ml) than lesions who remained PET-2 positive (3.84; 7ml). Conclusion: In this study with pediatric HL patients, the complete response rate in PET-2 of skeletal and nodal involvement was similar. Bone flare seemed to be irrelevant. Overall, the current skeletal PET response criterion - comparison with the local skeletal background - is well suited. Initial uptake intensity and MTV of skeletal lesions were predictive for the PET-2 result. Higher values for both parameters were associated with a worse PET-2 response.

PMID: 29653979 [PubMed - as supplied by publisher]




Potential impact of 68Ga-PSMA-11 PET/CT on prostate cancer definitive radiation therapy planning.
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Potential impact of 68Ga-PSMA-11 PET/CT on prostate cancer definitive radiation therapy planning.

J Nucl Med. 2018 Apr 13;:

Authors: Calais J, Kishan AU, Cao M, Fendler WP, Eiber M, Herrmann K, Ceci F, Reiter RE, Matthew RB, Hegde JV, Shaverdian N, King CR, Steinberg ML, Czernin J, Nickols NG

Abstract
Background: Standard-of-care imaging for initial staging of prostate cancer (PCa) underestimates disease burden. Prostate specific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) detects PCa metastasis with superior accuracy with potential impact definitive radiation therapy (RT) planning for non-metastatic PCa. Objectives: i) To determine how often definitive PCa RT planning based on standard target volumes cover 68Ga-PSMA-11 PET/CT defined disease, and ii) To assess the potential impact of 68Ga-PSMA-11 PET/CT on definitive PCa RT planning. Patients and Methods: This is a post-hoc analysis of an intention to treat population of 73 patients with localized PCa without prior local therapy who underwent 68Ga-PSMA PET/CT for initial staging as part of an Investigational New Drug trial. 11/73 were intermediate-risk (15%), 33/73 were high-risk (45%), 22/73 were very high risk (30%), and 7/73 were N1 (9.5%). Clinical target volumes (CTVs) that included the prostate, seminal vesicles, and pelvic lymph nodes (LNs) using Radiation Therapy Oncology Group (RTOG) consensus guidelines were contoured on the CT portion of the PET/CT by a radiation oncologist blinded to the PET findings. 68Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. PSMA-positive lesions not covered by planning volumes based on the CTVs were considered to have a major potential impact on treatment planning. Results: All patients had PSMA-positive primary prostate lesion(s). 25/73 (34%) and 7/73 (9.5%) had PSMA-positive pelvic nodal and distant metastases, respectively. The sites of nodal metastases in decreasing order of frequency were external iliac (20.5%), common iliac (13.5%), internal iliac (12.5%) obturator (12.5%), perirectal (4%), abdominal (4%), upper-diaphragm (4%), and presacral (1.5%). The median size of the nodal lesions was 6 mm (range 4-24 mm). RT planning based on the CTVs covered 69/73 (94.5%) of primary disease and 20/25 (80%) of pelvic nodal disease, on a per-patient analysis. Conclusion:68Ga-PSMA-11 PET/CT had a major impact on intended definitive PCa RT planning in 12/73 of patients (16.5%) when RT fields covered the prostate, seminal vesicles and the pelvic LNs, and in 25/66 of patients (37%) when RT fields covered only the prostate and seminal vesicles (without pelvic LNs).

PMID: 29653978 [PubMed - as supplied by publisher]




Radioactive Iodine Therapy for Differentiated Thyroid Cancer: Lessons from Confronting Controversial Literature on Risks for Secondary Malignancy.
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Radioactive Iodine Therapy for Differentiated Thyroid Cancer: Lessons from Confronting Controversial Literature on Risks for Secondary Malignancy.

J Nucl Med. 2018 Apr 13;:

Authors: Tulchinsky M, Binse I, Campennì A, Dizdarevic S, Giovanella L, Jong I, Kairemo K, Kim CK

PMID: 29653977 [PubMed - as supplied by publisher]




Reply: 6"-18F-Fluoromaltotriose PET Evaluation in Escherichia-Coli-Induced Myositis: is there Uptake Saturation in Control?
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Reply: 6"-18F-Fluoromaltotriose PET Evaluation in Escherichia-Coli-Induced Myositis: is there Uptake Saturation in Control?

J Nucl Med. 2018 Apr 13;:

Authors: Wardak M, Gowrishankar G, Gambhir SS

PMID: 29653976 [PubMed - as supplied by publisher]




Predictive factors of response and overall survival in patients with castration-resistant metastatic prostate cancer undergoing 177Lu-PSMA therapy.
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Predictive factors of response and overall survival in patients with castration-resistant metastatic prostate cancer undergoing 177Lu-PSMA therapy.

J Nucl Med. 2018 Apr 13;:

Authors: Ahmadzadehfar H, Essler M

PMID: 29653975 [PubMed - as supplied by publisher]




Development and validation of a rebinner with rigid motion correction for the Siemens PET-MR scanner: Application to a large cohort of [11C]-PIB scans.
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Development and validation of a rebinner with rigid motion correction for the Siemens PET-MR scanner: Application to a large cohort of [11C]-PIB scans.

J Nucl Med. 2018 Apr 13;:

Authors: Reilhac A, Merida I, Irace Z, Stephenson M, Weekes A, Chen C, Totman J, Townsend DW, Fayad H, Costes N

Abstract
Objective: Head motion occuring during brain PET studies leads to image blurring and to bias in measured local quantities. Our first objective was to implement an accurate list-mode-based rigid motion correction method for PET data acquired with the mMR synchronous Positron Emission Tomography/Magnetic Resonance (PET/MR) scanner. Our second objective was to optimize the correction for [11C]-PIB scans using simulated and actual data with well-controlled motions. Results: An efficient list-mode based motion correction approach has been implemented, fully optimized and validated using simulated as well as actual PET data. The average spatial resolution loss induced by inaccuracies in motion parameter estimates as well as by the rebinning process was estimated to correspond to a 1 mm increase in Full Width Half Maximum (FWHM) with motion parameters estimated directly from the PET data with a temporal frequency of 20 secs. The results show that it can be safely applied to the [11C]-PIB scans, allowing almost complete removal of motion induced artifacts.The application of the correction method on a large cohort of 11C-PIB scans led to the following observations: i) more than 21% of the scans were affected by a motion greater than 10 mm (39% for subjects with Mini-Mental State Examination -MMSE scores below 20) and ii), the correction led to quantitative changes in Alzheimer-specific cortical regions of up to 30%. Conclusion: The rebinner allows an accurate motion correction at a cost of minimal resolution reduction. The application of the correction to a large cohort of [11C]-PIB scans confirmed the necessity to systematically correct for motion for quantitative results.

PMID: 29653974 [PubMed - as supplied by publisher]




Radioiodinated Small Molecule Tyrosine Kinase Inhibitor for HER2 Selective SPECT Imaging.
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Radioiodinated Small Molecule Tyrosine Kinase Inhibitor for HER2 Selective SPECT Imaging.

J Nucl Med. 2018 Apr 13;:

Authors: Tang L, Peng C, Tang B, Li Z, Wang X, Li J, Gao F, Huang L, Xu D, Zhang P, Zhuang R, Su X, Chen X, Zhang X

Abstract
Objectives: One of the most clinically relevant molecular aberrations in breast cancer is the overexpression of human epidermal growth factor receptor type 2 (HER2). We aimed to develop a radiolabeled tyrosine kinase inhibitor (TKI) for HER2 targeted breast cancer imaging. In this study, a radioiodinated analog (125/131I-IBA-CP) of the HER2 selective inhibitor CP724,714 was prepared and evaluated in HER2 positive or negative subcutaneous human breast cancer xenografts. Methods: The CP724,714 analog IBA-CP was synthesized and assayed for its inhibitory activities against HER2 and six other tyrosine kinases. 125/131I-IBA-CP was prepared using a copper-mediated radioiodination method with enhanced labeling yield and molar activity. In vitro biological activities, including specific and nonspecific binding of 131I-IBA-CP to its HER2 kinase target were assessed in different cell lines. In vivo microSPECT imaging with 125I-IBA-CP and biodistribution studies were conducted in mice bearing HER2-positive, HER2-negative or epidermal growth factor receptor (EGFR)-positive tumors. Nonradioactive IBA-CP and the EGFR inhibitor erlotinib were employed as blocking agents to investigate the binding specificity and selectivity of 125/131I-IBA-CP toward HER2 in vitro and in vivo. Additionally, 125/131I-ICP was prepared by direct radioiodination of CP724,714 for comparison with 125/131I-IBA-CP. Results: IBA-CP displayed good in vitro inhibitory activity (IC50 = 16 nM) and selectivity for HER2 over six other cancer-related tyrosine kinases. 125/131I-IBA-CP was prepared in a typical radiochemical yield of about 65% (decay-corrected), radiochemical purity of >98%, and molar activity of 42 GBq/μmol at the end of synthesis. SPECT imaging revealed significantly higher uptake of 125I-IBA-CP than 125I-ICP in the HER2-positive MDA-MB-453 tumor. Uptake in the HER2-negative MCF-7 tumor was much lower. Binding of 125I-IBA-CP in the MDA-MB-453 tumor was blocked by co-injection with an excess amount of IBA-CP, but not by erlotinib. Conclusion: The radiolabeled HER2 selective inhibitor 125/131I-IBA-CP is a promising probe for in vivo detection of HER2-positive tumors.

PMID: 29653973 [PubMed - as supplied by publisher]




FDG-PET/CT in autosomal dominant polycystic kidney disease patients with suspected cyst infection.
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FDG-PET/CT in autosomal dominant polycystic kidney disease patients with suspected cyst infection.

J Nucl Med. 2018 Apr 13;:

Authors: Pijl JP, Glaudemans AWJM, Slart RHJA, Kwee TC

Abstract
Purpose: To determine the value of 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) for diagnosing renal or hepatic cyst infection in patients with autosomal dominant polycystic kidney disease (ADPKD). Methods: This retrospective single-center study included all patients with ADPKD who underwent FDG-PET/CT because of suspected cyst infection between 2010 and 2017. Results: Thirty FDG-PET/CT scans of thirty individual patients were included, of which 19 were positive for cyst infection. According to a previously established clinical and biochemical reference standard, FDG-PET/CT achieved sensitivity of 88.9%, specificity of 75.0%, positive predictive value of 84.2%, and negative predictive value of 81.8% for the diagnosis of cyst infection. In 5 cases, FDG-PET/CT suggested a different pathologic process that explained the symptoms, including pneumonia (n = 1), generalized peritonitis (n = 1), pancreatitis (n = 1), colitis (n = 1), and cholangitis (n = 1). Total duration of hospital stay and duration between FDG-PET/CT scan and hospital discharge of patients with an FDG-PET/CT scan positive for cyst infection were significantly longer than those with a negative scan (P = 0.005 and P = 0.009, respectively). Creatinine levels were significantly higher in patients with an FDG-PET/CT scan positive for cyst infection than in patients with a negative scan (P = 0.015). Other comparisons of clinical parameters (age, gender, presence of fever (>38.5°C) for more than 3 days, abdominal pain, history of solid organ transplantation and nephrectomy, immune status), laboratory values (C-reactive protein level (CRP), leukocyte count, estimated glomerular filtration rate), and microbiologic results (blood and urine cultures) were not significantly different (P = 0.13-1.00) between FDG-PET/CT-positive and -negative patients. Conclusion: FDG-PET/CT is a useful and recommendable (upfront) imaging modality for the evaluation of patients with ADPKD and suspected cyst infection.

PMID: 29653972 [PubMed - as supplied by publisher]




Safety, Pharmacokinetics and Dosimetry of a Long-Acting Radiolabeled Somatostatin Analogue 177Lu-DOTA-EB-TATE in Patients with Advanced Metastatic Neuroendocrine Tumors.
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Safety, Pharmacokinetics and Dosimetry of a Long-Acting Radiolabeled Somatostatin Analogue 177Lu-DOTA-EB-TATE in Patients with Advanced Metastatic Neuroendocrine Tumors.

J Nucl Med. 2018 Apr 13;:

Authors: Zhang J, Wang H, Jacobson Weiss O, Cheng Y, Niu G, Li F, Bai C, Zhu Z, Chen X

Abstract
Radiolabeled somatostatin analogue therapy has become an established treatment method for patients with well to moderately differentiated unresectable or metastatic neuroendocrine tumors (NETs). The most frequently used somatostatin analogues in clinical practice are octreotide and octreotate. However, both peptides showed suboptimal retention within tumors. The aim of this first-in-human study is to explore the safety and dosimetry of a long-acting radiolabeled somatostatin analogue, lutetium-177-1, 4, 7, 10-tetra-azacyclododecane-1, 4, 7, 10-tetraacetic acid-Evans blue-octreotate (177Lu-DOTA-EB-TATE). Methods: Eight patients (6 males and 2 females; age range, 27-61 y) with advanced metastatic neuroendocrine tumors were recruited. Five patients received a single dose 0.35-0.70 GBq (9.5-18.9 mCi) of 177Lu-DOTA-EB-TATE and underwent serial whole body planar and single-photon emission computed tomography-computed tomography (SPECT-CT) scans at 2, 24, 72, 120 and 168 h after injection. The other 3 patients received intravenous injection of 0.28-0.41 GBq (7.5-11.1 mCi) of 177Lu-DOTATATE for the same imaging acquisition procedures at 1, 3, 4, 24 and 72 h after injection. The dosimetry was calculated using the OLINDA/EXM 1.1 software. Results: Administration of 177Lu-DOTA-EB-TATE was well tolerated, with no adverse symptoms being noticed or reported in any of the patients. Compared with 177Lu-DOTATATE, 177Lu-DOTA-EB-TATE showed extended circulation in the blood and achieved 7.9-fold increase of tumor dose delivery. The total body effective doses were 0.205 ± 0.161 mSv/MBq for 177Lu-DOTA-EB-TATE and 0.174 ± 0.072 mSv/MBq for 177Lu-DOTATATE. Significant dose delivery increases to the kidneys and bone marrow were also observed in patients receiving 177Lu-DOTA-EB-TATE than those receiving 177Lu-DOTATATE (3.2 and 18.2-fold, respectively). Conclusion: By introducing an albumin binding moiety, 177Lu-DOTA-EB-TATE showed remarkably higher uptake and retention in NET tumors as well as significantly increased accumulation in the kidneys and red marrow. It has great potential to be used in PRRT for NET tumors with lower dose and less frequency of administration.

PMID: 29653971 [PubMed - as supplied by publisher]