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1.  Alkylphosphocholine Analogs for Broad-Spectrum Cancer Imaging and Therapy 
Science translational medicine  2014;6(240):240ra75.
Many solid tumors contain an overabundance of phospholipid ethers relative to normal cells. Capitalizing on this difference, we created cancer-targeted alkylphosphocholine (APC) analogs through structure-activity analyses. Depending on the iodine isotope used, radioiodinated APC analog CLR1404 was used as either a positron emission tomography (PET) imaging (124I) or molecular radiotherapeutic (131I) agent. CLR1404 analogs displayed prolonged tumor-selective retention in 55 in vivo rodent and human cancer and cancer stem cell models. 131I-CLR1404 also displayed efficacy (tumor growth suppression and survival extension) in a wide range of human tumor xenograft models. Human PET/CT (computed tomography) and SPECT (single-photon emission computed tomography)/CT imaging in advanced-cancer patients with 124I-CLR1404 or 131I-CLR1404, respectively, demonstrated selective uptake and prolonged retention in both primary and metastatic malignant tumors. Combined application of these chemically identical APC-based radioisosteres will enable personalized dual modality cancer therapy of using molecular 124I-CLR1404 tumor imaging for planning 131I-CLR1404 therapy.
doi:10.1126/scitranslmed.3007646
PMCID: PMC4336181  PMID: 24920661
2.  Phospholipid Ether Analogs for the Detection of Colorectal Tumors 
PLoS ONE  2014;9(10):e109668.
The treatment of localized colorectal cancer (CRC) depends on resection of the primary tumor with adequate margins and sufficient lymph node sampling. A novel imaging agent that accumulates in CRCs and the associated lymph nodes is needed. Cellectar Biosciences has developed a phospholipid ether analog platform that is both diagnostic and therapeutic. CLR1502 is a near-infrared fluorescent molecule, whereas 124/131I-CLR1404 is under clinical investigation as a PET tracer/therapeutic agent imaged by SPECT. We investigated the use of CLR1502 for the detection of intestinal cancers in a murine model and 131I-CLR1404 in a patient with metastatic CRC. Mice that develop multiple intestinal tumors ranging from adenomas to locally advanced adenocarcinomas were utilized. After 96 hours post CLR1502 injection, the intestinal tumors were analyzed using a Spectrum IVIS (Perkin Elmer) and a Fluobeam (Fluoptics). The intensity of the fluorescent signal was correlated with the histological characteristics for each tumor. Colon adenocarcinomas demonstrated increased accumulation of CLR1502 compared to non-invasive lesions (total radiant efficiency: 1.76×1010 vs 3.27×109 respectively, p = 0.006). Metastatic mesenteric tumors and uninvolved lymph nodes were detected with CLR1502. In addition, SPECT imaging with 131I-CLR1404 was performed as part of a clinical trial in patients with advanced solid tumors. 131I-CLR1404 was shown to accumulate in metastatic tumors in a patient with colorectal adenocarcinoma. Together, these compounds might enhance our ability to properly resect CRCs through better localization of the primary tumor and improved lymph node identification as well as detect distant disease.
doi:10.1371/journal.pone.0109668
PMCID: PMC4186834  PMID: 25286226
3.  18F-DOPA PET with and without MRI fusion, a receiver operator characteristics comparison 
This study is a retrospective analysis of the diagnostic accuracy of FDOPA PET with MRI fusion to FDOPA PET without MRI fusion. Clinical FDOPA PET scans obtained between 2000 and 2008 at the University of Wisconsin Hospital and Clinics were assessed using measures derived from regions of interest (ROI) generated with fused MRI (fused group) and again with ROIs derived solely from PET data (non-fused groups). The ROIs were used to calculate ratios (Striatum/Occipital cortex, Striatum/Cerebellum) pertinent to Parkinson’s disease (PD) pathology. The clinical records were assessed for demographic data, follow-up length, and diagnosis. Receiver Operator Characteristics with area under the curve (AUC) measures were calculated and compared using confidence intervals and hypothesis testing. 27 patients had FDOPA PET with median clinical follow-up of 4 years. Of these, 17 patients had FDOPA PET with a fusible MR image. Seven of the 27 had a non-PD movement disorder. AUCs for the ratio measures ranged from 0.97-1.0 (fused), 0.73-0.83 (non-fused), and 0.63-0.82 (matched non-fused). The fused images had improved accuracy compared to the matched non-fused and all non-fused groups for the striatum to occipital group (p=0.04, p=0.03), while the striatum to cerebellum ratio had improvement over the non-fused all group (p=0.041). MR fusion to FDOPA PET improves the accuracy of at least some measures (Striatum/Occiput, Striatum/Cerebellum) in the diagnosis of PD.
PMCID: PMC3484423  PMID: 23145363
18F-Fluorodopa; positron emission tomography; image fusion; receiver operator characteristics; Parkinson’s
4.  Surgical decision making in Temporal Lobe Epilepsy (TLE): a comparison of 18Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET), MRI, and EEG 
Epilepsy & behavior : E&B  2011;22(2):293-297.
Purpose
(1) Determine the effect of 18Fluorodeoxyglucose Positron Emission Tomography (FDG-PET), magnetic resonance imaging (MRI), and electroencephalogram (EEG) on the decision for temporal lobe epilepsy (TLE) surgery. (2) Determine if FDG-PET, MRI, or EEG predict surgical outcome.
Procedures
All PET scans ordered (2000–2010) for epilepsy or seizure were tabulated. Medical records were investigated to determine eligibility and collect data. Statistical analysis included odds ratios, kappa statistics, univariate analysis, and logistic regression.
Results
186 patients had an FDG-PET, 124 patients had TLE, 50 were surgical candidates, and 27 had operations with > 6 months follow-up. Median length of follow-up was 24 months. MRI, FDG-PET, and EEG were significant predictors of surgical candidacy (p<0.001) with odds ratio of 42.8, 20.4, and 6.3 respectively. PET was the only significant predictor of post-operative outcome. (p<0.01)
Conclusion
MRI had a trend toward most influence on surgical candidacy, but only FDG-PET predicted the surgical outcome.
doi:10.1016/j.yebeh.2011.06.022
PMCID: PMC3260654  PMID: 21798813
temporal lobe epilepsy; medication refractory epilepsy; epilepsy surgery; fluorodeoxyglucose (FDG); positron emission tomography (PET); magnetic resonance imaging (MRI); Electroencephalogram (EEG)
5.  Impact of expectation-maximization reconstruction iterations on the diagnosis of temporal lobe epilepsy with PET 
There is a well known tradeoff between image noise and image sharpness that is dependent on the number of iterations performed in ordered subset expectation maximization (OSEM) reconstruction of PET data. We aim to evaluate the impact of this tradeoff on the sensitivity and specificity of 18F-FDG PET for the diagnosis of temporal lobe epilepsy. A retrospective blinded reader study was performed on two OSEM reconstructions, using either 2 or 5 iterations, of 32 18F-FDG PET studies acquired at our institution for the diagnosis of temporal lobe epilepsy. The sensitivity and specificity of each reconstruction for identifying patients who were ultimately determined to be surgical candidates was assessed using an ROC analysis. The sensitivity of each reconstruction for identifying patients who showed clinical improvement following surgery was also assessed. Our results showed no significant difference between the two reconstructions studied for either the sensitivity and specificity of 18F-FDG PET for predicting surgical candidacy, or its sensitivity for predicting positive surgical outcomes. This implies that the number of iterations performed during OSEM reconstruction will have little impact on a reader based interpretation of 18F-FDG PET scans acquired for the diagnosis of temporal lobe epilepsy, and can be determined by physician and institutional preference.
PMCID: PMC3477742  PMID: 23133820
18F-FDG PET; temporal lobe epilepsy; OSEM reconstruction; ROC analysis

Results 1-5 (5)