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We show that this method yields an exaggerated P value and overestimates the prognostic impact of the biomarker. We illustrate that the degree of the optimistic bias increases with the number of variables being considered in a risk model. Finally, we discuss methods to appropriately ascertain the additional prognostic contribution of the new biomarker in disease settings where standard prognostic factors already exist. Throughout the article, we use real examples in oncology to highlight relevant methodologic issues, and when appropriate, we use simulations to illustrate more abstract statistical concepts.Objective Non-catechol based high affinity selective dopamine D1 receptor (D1R) agonists were recently described, and candidate PET ligands were selected based on favorable properties. The objective of this study was to characterize in vivo in non-human primates two novel D1R agonist PET radiotracers, racemic 18F-MNI-800 and its more active atropisomeric (-)-enantiomer 18F-MNI-968. Methods Ten brain PET experiments were conducted with 18F-MNI-800 in two adult rhesus macaques and two adult cynomolgus macaques, and eight brain PET experiments were conducted with 18F-MNI-968 in two adult rhesus macaques and two adult cynomolgus macaques. PET data were analyzed with both plasma-input and reference-region based methods. Whole-body PET images were acquired with 18F-MNI-800 for radiation dosimetry estimates in two adult rhesus macaques. Results18F-MNI-800 and 18F-MNI-968 exhibited regional uptake consistent with D1 receptor distribution. Specificity and selectivity were demonstrated by dose-dependent blocking with the D1 antagonist SCH-23390. 18F-MNI-968 showed a 30% higher specific signal compared to 18F-MNI-800, with a binding potential BPND of ~0.3 in the cortex and ~1.1 in the striatum. Dosimetry radiation exposure was favorable, with an effective dose of ~0.023 mSv/MBq. Conclusion18F-MNI-968 (18F-PF-0110) has significant potential as a D1R agonist PET radiotracer, and further characterization in human subjects is warranted.PURPOSE To determine whether quantitative PET parameters on baseline 68Ga-DOTATATE PET/CT (bPET) and interim PET (iPET) performed prior to second cycle of therapy are predictive of therapy response and progression free survival (PFS). PATIENTS & METHODS Ninety-one patients with well-differentiated neuroendocrine tumors (mean Ki67, 8.3%) underwent 68Ga-DOTATATE PET/CT (DT- PET) to determine suitability for peptide receptor radionuclide therapy (PRRT) as part of a prospective multicenter study. Mean follow-up was 12.2 months. Of them, 36 patients had iPET. Tumor metrics evaluated 1. Marker lesion-based measures mean SUVmax and ratio to liver/spleen; 2. click here Segmented DT tumor volume (DTTV) measures DTTV; SUVmax and SUVmean using liver and spleen as thresholds; 3. Heterogeneity parameters (coefficient of variance, kurtosis, and skewness). Wilcoxon rank sum test was used for association between continuous variables and therapy response as determined by clinical response. Univariable and multivariable Cox proportional r PFS. Change in these parameters after first cycle of PRRT did not correlate with clinical outcomes.Purpose68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3 are somatostatin receptor subtype 2 (SSTR2) specific antagonists used for PET/CT imaging. The purpose of this study was to evaluate the safety, biodistribution, and dosimetry of 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3 in patients with well-differentiated neuroendocrine tumors (NETs). Methods Patients were equally randomized into two arms Arm A, 68Ga-NODAGA-LM3; Arm B, 68Ga-DOTA-LM3. Serial PET scans were acquired at 5, 15, 30, 45, 60, and 120 minutes after 68Ga-NODAGA-LM3 (200 MBq ± 11 MBq/40 μg total peptide mass) or 68Ga-DOTA-LM3 (172 MBq ± 21 MBq/40 μg total peptide mass) injection. The biodistribution in normal organs, tumor uptake, and safety were assessed. Radiation dosimetry was calculated using OLINDA/EXM (version 1.0). Results Sixteen patients, 8 in each arm, were recruited in the study. Both tracers were well tolerated in most patients. Two patients in Arm B had nausea (G2) and one of them had vomiting (G1). The PET images of other fourteen patients were further anake, and good tumor retention, resulting in high image contrast. The dosimetric data is comparable to other 68Ga-labeled SSTR2 antagonists. Further studies are required to look into the potential antagonistic effects of 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3.Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodesoxyglucose (FDG) is an integral component in the primary staging of most lymphomas. However, its utility is limited in marginal zone lymphoma (MZL) due to inconsistent FDG avidity. One diagnostic alternative could be the targeting of CXC-motif chemokine receptor 4 (CXCR4), shown to be expressed by MZL cells. This study investigated the value of adding CXCR4-directed 68Ga-Pentixafor PET/CT to conventional staging. Methods 22 newly diagnosed MZL patients were staged conventionally and with 68Ga-Pentixafor PET/CT. Lesions exclusively identified by 68Ga-Pentixafor PET/CT were biopsied as standard of reference and compared to imaging results. The impact of CXCR4-directed imaging on staging results and treatment protocol was assessed. Results68Ga-Pentixafor PET/CT correctly identified all patients with viable MZL and was superior to conventional staging (P less then 0.001). CXCR4-directed imaging results were validated by confirmation of MZL in 21/24 PET-guided biopsy samples. Inclusion of 68Ga-Pentixafor PET/CT in primary staging significantly impacted staging results in almost half, and treatment protocols in one third of patients (upstaging, n = 7; downstaging, n = 3; treatment change, n = 8; P less then 0.03). Conclusion68Ga-Pentixafor PET/CT is a suitable tool in primary staging of MZL and holds the potential to improve existing diagnostic algorithms.The genetic code to life is balanced on a string of DNA that is under constant metabolic and physical stress from environmental forces. Nearly all diseases have a genetic component caused by or resulting in DNA damage that alters biology to drive pathogenesis. Recent advancements in DNA repair biology have led to the development of imaging tools that target DNA damage response and repair proteins. PET has been used for early detection of oncogenic processes and monitoring of tumor response to chemotherapeutics that target the DNA repair machinery. In the field of precision medicine, imaging tools provide a unique opportunity for patient stratification by directly measuring drug target expression or monitoring therapy to identify early responders. This overview discusses the state of the art on molecular imaging of DNA damage and repair from the past 5 years, with an emphasis on poly[adenosine diphosphate ribose]polymerase-1 as an imaging target and predictive biomarker of response to therapy.