ALBERT

Description: Malignant melanoma has one of the highest mortality rates of any cancer because of its aggressive nature and high metastatic potential. Clinical staging of the disease at the time of diagnosis is very important for the prognosis and outcome of melanoma treatment. In this study, we designed and synthesized the18F-labeled pyridine-based benzamide derivativesN-(2-(dimethylamino)ethyl)-5-[18F]fluoropicolinamide ([18F]DMPY2) andN-(2-(dimethylamino)ethyl)-6-[18F]fluoronicotinamide ([18F]DMPY3) to detect primary and metastatic melanoma at an early stage and evaluated their performance in this task. [18F]DMPY2 and [18F]DMPY3 were synthesized by direct radiofluorination of the bromo precursor, and radiochemical yields were ∼15–20%. Cell uptakes of [18F]DMPY2 and [18F]DMPY3 were 〉103-fold and 18-fold higher, respectively, in B16F10 (mouse melanoma) cells than in negative control cells. Biodistribution studies revealed strong tumor uptake and retention of [18F]DMPY2 (24.8% injected dose per gram of tissue [ID/g] at 60 min) and [18F]DMPY3 (11.7%ID/g at 60 min) in B16F10 xenografts. MicroPET imaging of both agents demonstrated strong tumoral uptake/retention and rapid washout, resulting in excellent tumor-to-background contrast in B16F10 xenografts. In particular, [18F]DMPY2 clearly visualized almost all metastatic lesions in lung and lymph nodes, with excellent image quality. [18F]DMPY2 demonstrated a significantly higher tumor-to-liver ratio than [18F]fluorodeoxyglucose ([18F]FDG) and the previously reported benzamide tracersN-[2-(diethylamino)-ethyl]-5-[18F]fluoropicolinamide ([18F]P3BZA) andN-[2-(diethylamino)-ethyl]-4-[18F]fluorobenzamide ([18F]FBZA) in B16F10-bearing or SK-MEL-3 (human melanoma)-bearing mice. In conclusion, [18F]DMPY2 might have strong potential for the diagnosis of early stage primary and metastatic melanoma using positron emission tomography (PET).

Description: FDG-PET, a functional imaging modality used for staging and monitoring response to treatment of malignant lymphoma, has a higher sensitivity and specificity than conventional imaging. PET/CT may be more accurate than conventional imaging in assessing treatment effects to correctly identify patients with residual disease and predict therapy outcomes. We prospectively investigated that PET/CT may provide additional prognostic information in mid-response assessment prior to completion of chemotherapy. Patients and Method: Eighty-six newly diagnosed patients with malignant lymphoma were enrolled from Aug. 2004 to July 2006. Both CT and PET/CT analysis were performed at the time of diagnosis and after the 3rd or 4th chemotherapy. The clinical stage of the patients was assessed according to International Workshop Criteria (IWC). PET/CT imaging was analyzed according to the combination of morphology using the CT portion and by the uptake and location of the FDG-PET portion. The cut off value of the positive in PET/CT was more than max SUV 3.0. We divided them into four different response groups using IWC and PET/CT (CRu-negative, Cru-positive, PR-negative, PR-positive). The limited-stage patients were treated with chemotherapy and involved field radiation therapy and the advanced-stage patients were treated with eight cycles of chemotherapy. However, advanced-stage patients who were older than sixty, if they had CRu-negative in interim analysis, were treated with only six cycles. Results: Median age was 53.5 years (range: 19 – 85). Seventy five patients had Non-Hodgkin’s lymphoma [Indolent-11 (12.8%), Aggressive-64 (74.4%)] and eleven patients (12.8%) had Hodgkin’s lymphoma. Forty-two patients (48.8%) achieved CRu-negative, 6 patients (7.0%) achieved CRu-positive, 20 patients (23.3%) achieved PR-negative and 18 patients (20.9%) showed PR-positive by interim IWC and PET/CT. The relapse rate is significantly different between PET-positive (58.3%) and PET-negative (8.1%) (P=0.000), especially when 12 of 18 patients in PR-positive group (66.7%) relapsed after or during chemotherapy. Figures showed the Kaplan-Meier estimates of overall and progression free survival of 86 patients depending on the combined evaluation of interim IWC and PET/CT. Conclusion: Interim PET/CT analysis was a significantly predictive value of disease progression and survival. The patients with PR-positive according to interim IWC and PET/CT analysis should be considered for an intensive therapeutic plan. Figure Figure

Description: Purpose Although interim 18F-fluoro-2-dexoy-D-glucose-positron emission tomography (FDG-PET)/computerized tomography (CT) scan has emerged as a powerful prognostic tool in predicting treatment outcome in Hodgkin's lymphoma (HL) and diffuse large B cell lymphoma (DLBCL), the prognostic value of interim PET/CT scanning has not been determined in peripheral T cell lymphomas (PTCLs). We prospectively investigated the sequential interim PET/CT to determine whether it provided additional prognostic information for the treatment of PTCLs. Patients and Methods Sixty-three patients with newly diagnosed PTCL were enrolled from Sep. 2006 to Nov. 2011 (ClinicalTrials.gov Identifier: NCT01470066). PET/CT scan was performed at the time of diagnosis, mid-treatment and the completion of CHOP/CHOP-like or non-anthracycline-based chemotherapy. The initial stage and final response were assessed according to the revised International Workshop Criteria (IWC). The response of interim PET/CT was assessed by combined evaluation with visual analysis using Deauville five-point scale (5-PS), quantitative assessment of the maximal standardized uptake value reduction rate (delta SUVmax) and quantitative assessment of metabolic tumor volume reduction rate (delta MTV2.5). To evaluate the optimal cutoff value of delta SUVmax or delta MTV2.5 for predicting the disease progression, receiver-operating characteristic (ROC) analysis was performed. Results Median age was 60 years (range: 20-81). 39 patients (61.9%) presented with advanced stage and 18 (28.6%) had bone marrow involvements. The histological subtypes were 27% PTCL-unspecified (n=17), 15.9% AITL (n=10), 42.9% NK/T cell (n=27), and others. At diagnosis, 31 patients (49.2%) were classified as high-risk by the international prognostic index (IPI) and 29 (46%) were classified as high-risk (more than 2 factors) by the prognostic index for PTCL (PIT). 59 patients could be evaluated for the interim response with 7.9% of treatment-related mortality. After following median 40.3 months (range, 12.8-83.2), more than grade 3 in Deauville 5-PS, the optimal cutoff value of delta SUVmax and the optimal cutoff value of delta MTV2.5 could differentiate the patients for predicting the disease progression with high positive predictive value (87.8%, 92.3% and 92.8%, respectively). Patients with more than grade 3 based on 5-PS had significantly poor prognosis compared to patients with grade1-2 (P=0.000). In addition, the 3-year PFS rates were significantly different between patients with delta SUVmax°Â67.6% or delta MTV2.5°Â98.7% and patients with above the optimal cutoff value of delta SUVmax or delta MTV2.5, respectively (P=0.001). Seven patients with interim PET-positive uptakes (more than grade 3) were revealed with false-positive uptakes and three patients were with false-negative by locoregional biopsy. Conclusions The visual, quantitative SUV-based and MTV-based assessment in mid-treatment interim PET/CT had a significant predictive value for disease progression and three parameters could have a high differential potential for predicting the prognosis in patients with PTCLs. Disclosures: No relevant conflicts of interest to declare.

Description: Purpose : This study evaluated the prognostic role of 18F-FDG PET/CT at baseline in patients with newly diagnosed multiple myeloa (MM) and evaluated the prognostic relevance of 18F-FDG PET/CT for each stage according to the Revised International Staging System (R-ISS). Method: We retrospectively analyzed the records of 167 patients with newly diagnosed MM. 18F-FDG PET/CT was performed prior to induction therapy in patients with newly diagnosed MM. A Focal lesions (FL) at diagnosis was defined as focally increased FDG uptake greater than the physiologic bone marrow or liver uptake, with or without any underlying lesion. Extramedullary disease (EMD) was defined as FDG-avid soft tissue that was not contiguous to bone. Results: A total of 102 patients (61.1%) had at least one FL at diagnosis, and 44.9% had more than three FLs. EMD was present in 13.2% of all patients. In the total cohort, the presence of more than three hypermetabolic FLs or EMD on baseline PET/CT was associated with significantly inferior progression free survival (PFS) and overall survival (OS) than other patients. Because most patients (91%) with EMD had more than three FLs, PET/CT positivity was defined as the presence of more than three FLs or the presence of EMD. The C-reactive protein level was higher (0.550 vs. 0.245 mg/L, P = 0.004) and the serum albumin level was lower in the PET/CT-positive group (3.5 vs. 3.6 g/dL, P = 0.040). Patients who were PET/CT-positive had a significantly lower complete response rate after first-line therapy compared with those who were PET/CT-negative (15.6% vs. 34.4%, P = 0.007). In multivariate analyses, PET/CT positivity was an independent predictor of PFS and OS in all patients. Fifty-five patients (46.1%) with R-ISS II were PET/CT-positive at baseline and had significantly shorter PFS and OS. PET/CT positivity was also correlated with poor PFS and OS in patients with R-ISS III. Conclusion : 18F-FDG PET/CT was an independent predictor of survival outcomes in patients with newly diagnosed MM. In addition, performing 18F- FDG PET/CT at diagnosis may be useful for determining the survival outcomes of MM patients with R-ISS II and III. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 1799 18F-fluoro-2-dexoy-D-glucose-positron emission tomography (FDG-PET)/computerized tomography (CT) has been used for staging and monitoring responses to treatment in patients with diffuse large B cell lymphoma (DLBCL). The sequential interim PET/CT was prospectively investigated to determine whether it provided additional prognostic information and could be a positive predictable value within patients with the same international prognostic index (IPI) after the use of rituximab in DLBCL. Patients and methods: One hundred and sixty-one patients with newly diagnosed DLBCL were enrolled between August 2004 and December 2009 at a single institution. The assessment of the PET/CT was performed at the time of diagnosis and mid-treatment of R-CHOP chemotherapy. The clinical stage and response of the patients were assessed according to revised response criteria for aggressive lymphomas (Cheson, J Clin Oncol, 2007). The positivity of interim PET/CT was determined based on the semi-quantitative assessment of the maximal standardized uptake value (SUVmax cut-off value of 3.0). Results: Sixty-seven patients (41.6%) presented in advanced stage disease and 27 (16.8%) had bulky lesions. At diagnosis, 53 patients (32.9%) were classified as high/high-intermediate risk by the IPI and two patients could not check the interim response due to treatment-related mortality (TRM). Forty-three patients (26.7%) continued to have positive metabolic uptakes with a significantly high relapse rate (62.8%) compared to the patients with a negative interim PET/CT (12.1%) (P

Description: Abstract 2808 Although interim 18F-fluoro-2-dexoy-D-glucose-positron emission tomography (FDG-PET)/computerized tomography (CT) scan has emerged as a powerful prognostic tool in predicting treatment outcome in Hodgkin's lymphoma (HL) and diffuse large B cell lymphoma (DLBCL), the positive predictive value (PPV) of interim PET/CT scanning has not been determined in patients with peripheral T cell lymphoma (PTCL). The sequential interim PET/CT was prospectively investigated to determine whether it provided additional prognostic information and could be a positive predictable value for the treatment of PTCL. Patients and Methods: Fifty-five newly diagnosed patients with PTCL were enrolled from Sep. 2005 to July 2009 at a single institution. The PET/CT analysis was performed at the time of diagnosis and mid-treatment of CHOP/CHOP-like or other chemotherapy (EPOCH and IMEP). The clinical stage and response of the patients were assessed according to revised response criteria for aggressive lymphomas (Cheson, J Clin Oncol, 2007). The positivity of interim PET/CT was determined based on the semi-quantitative assessment of the maximal standardized uptake value (Cut-off SUVmax value of 3.0). Results: Median age was 55 years (range: 23–77). 31 patients (56.4%) presented in advanced stages and 13 (23.6%) had bone marrow involvements. The histological subtypes were 40.0% PTCL-unspecified (n=22), 5.1% angioimmunoblastic T cell (n=5), 38.2% nodal or extranodal NK/T cell (n=21), and others. At diagnosis, 24 patients (43.6%) were classified as high-risk by the international prognostic index (IPI) and 22 (40%) were classified as high-risk (more than 2 factors) by the prognostic index for PTCL (PIT). 47 patients could be assessed the interim response and 24 patients (43.6%) remained positive metabolic uptakes in interim PET/CT. The patients with positive interim PET/CT showed a significantly higher relapse rate (75.0%) than those with negative interim PET/CT (43.5%) (P =0.028). After following median 12.7 months, positivity of interim PET/CT was the prognostic factor for both OS and PFS, with a hazard ratio of 4.11 (1.30 – 13.01) and 3.26 (1.19 – 8.96), respectively. Six patients (10.9%) who determined to have positive interim PET/CT were revealed false-positive uptakes after locoregional biopsy (PPV of 0.75). Conclusions: Interim PET/CT has a significant predictive value for disease progression and survival of PTCL. The patients with positive interim PET/CT response should be considered an intensive therapeutic plan for overcoming their poor clinical outcome. Disclosures: No relevant conflicts of interest to declare.