Dosimetric Analysis of a Phase I Study of PSMA-Targeting Radiopharmaceutical Therapy With [177Lu]Ludotadipep in Patients With Metastatic Castration-Resistant Prostate Cancer.

OBJECTIVE: 177Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [177Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [177Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [177Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organ- and tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. RESULTS: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. CONCLUSION: [177Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

Prognostic value of TLR from FDG PET/CT in patients with margin-negative stage IB and IIA non-small cell lung cancer.

OBJECTIVES: To evaluate the prognostic value of TLR from PET/CT in patients with resection margin-negative stage IB and IIA non-small cell lung cancer (NSCLC) and compare high-risk factors necessitating adjuvant treatment (AT). METHODS: Consecutive FDG PET/CT scans performed for the initial staging of NSCLC stage IB and IIA were retrospectively reviewed. The maximum standardized uptake value (SUVmax) of the primary tumor and mean SUV of the liver were acquired. The tumor-to-liver SUV ratio (TLR) was also calculated. Charts were reviewed for basic patient characteristics and high-risk factors for considering AT (poor differentiation, visceral pleura invasion, vascular invasion, tumors > 4 cm, and wedge resection). Statistical analysis was performed using Cox regression analysis and the Kaplan-Meier method. RESULTS: Of the 112 patients included, 15 (13.4%) died, with a median overall survival (OS) of 43.8 months. Twenty-two patients (19.6%) exhibited recurrence, with median disease-free survival (DFS) of 36.0 months. In univariable analysis, pathology, poor differentiation, and TLR were associated with shorter DFS and OS. In multivariable analysis, TLR (hazard ratio [HR] = 1.263, p = 0.008) and differentiation (HR = 3.087, p = 0.012) were associated with shorter DFS. Also, TLR (HR = 1.422, p < 0.001) was associated with shorter OS. CONCLUSION: TLR from FDG PET/CT was an independent prognostic factor for recurrence and survival. PET parameters constitute risk factors for consideration in the decision-making for AT in margin-negative stage IB and IIA NSCLC. CLINICAL RELEVANCE STATEMENT: In this study, TLR from FDG PET/CT was an independent prognostic factor in stage IB-IIA non-small cell cancer patients. Although additional validation studies are warranted, TLR has the potential to be used to determine the need for adjuvant therapy. KEY POINTS: • High TLR is an independent poor prognostic factor in stage IB-IIA NSCLC. • Adjuvant treatment should be considered in patients with high TLR following complete tumor resection.

Predictive Value of Interim and End-of-Therapy 18F-FDG PET/CT in Patients with Follicular Lymphoma.

PURPOSE: 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is the standard imaging modality for response evaluation in FDG-avid lymphoma, but the prognostic value is not established in follicular lymphoma (FL). This study investigated the prognostic value of Deauville 5-point scale (D5PS) from paired interim PET/CT (PETInterim) and end-of-induction therapy PET/CT (PETEOI) in patients with FL. METHODS: FL staging and response assessment PET/CT images from 2013 to 2015 were retrospectively reviewed. PETInterim was performed 3 or 4 cycles after chemotherapy and PETEOI after 6 or 8 cycles. D5PS scores of 1, 2, and 3 were considered as negative (-), and scores 4 and 5 were considered as positive (+). Statistical analysis was done using Cox regression analysis, Kaplan-Meier survival analysis, and the log-rank test. RESULTS: Thirty-three patients with set of baseline, interim, and end-of-induction therapy PET/CT studies were included. Ten patients (30.3%) had progression. The median progression-free survival (PFS) was 38.8 months (range 3.5-72.7 months). On PETInterim, 23 patients were negative and 10 were positive. On PETEOI scans, 29 patients were negative, and 4 were positive. On multivariate analysis, PETEOI(-) was associated with longer PFS. PETInterim(+) and PETEOI(+) patients had a significantly shorter PFS than PETInterim(-) patients (39.9 months, 95% confidence interval [CI] 23.0-56.9, versus 55.5 months, 95% CI 49.7-61.2, p = 0.005) and PETEOI(-) patients (14.2 months, 95% CI 8.5-19.8, versus 60.5 months, 95% CI 52.1-69.0, p < 0.001). CONCLUSION: For patients with FL, PETInterim and PETEOI response is predictive of PFS, and PETEOI(+) is an independent prognostic factor for progression of FL.

Does FDG PET/CT have a role in determining adjuvant chemotherapy in surgical margin-negative stage IA non-small cell lung cancer patients?

PURPOSE: To evaluate the prognostic value of FDG PET/CT metabolic parameter compared to clinico-pathological risk factors in surgical margin-negative stage IA non-small cell lung cancer (NSCLC) patients. METHODS: 167 patients with consecutive FDG PET/CT scans from 2009 to 2015 performed for staging of NSCLC stage IA with plans for curative surgery were retrospectively reviewed. Maximum standardized uptake value (SUVmax) of primary tumor and mean SUV of liver were acquired from PET/CT. Tumor-to-liver SUV ratio (TLR) was calculated. Charts were reviewed to obtain basic patient characteristics (age, sex, smoking history, LDH, histologic subtype) and high-risk factors for adjuvant chemotherapy (tumor size, poorly differentiation, vascular invasion, and sub-lobar resection). Patients were dichotomized into two groups using optimal cut-off from receiver operating characteristic curve analysis of TLR to predict recurrence. Statistical analysis was done using Cox regression analysis and Kaplan-Meier method. Factors with P < 0.2 in univariate analysis were included in multivariate analysis. RESULTS: Recurrence rate was 12.6% (21/167). Median disease-free survival (DFS) was 47.2 months while 2-year and 5-year DFS rates were 93% and 86%, respectively. The optimal cut-off for TLR was 2.3. In univariate analysis, P value of sex, vascular invasion, and TLR were less than 0.2. In multivariable analysis, high TLR was the only factor that showed significant association with tumor recurrence (hazard ratio 3.795, P = 0.0048). CONCLUSIONS: TLR was an independent prognostic factor for recurrence and TLR could be an important risk factor to be considered in decision-making for adjuvant chemotherapy, even for those with stage IA NSCLC.

Prognostic Value of Pre- and Post-Treatment FDG PET/CT Parameters in Small Cell Lung Cancer Patients.

PURPOSE: To evaluate the prognostic value of PET parameters obtained from pre- and post-treatment FDG PET/CT examinations in patients with SCLC. METHODS: Fifty-nine patients with initially diagnosed SCLC from 2009 to 2014 were included and had chemotherapy and/or concurrent chemoradiotherapy. FDG PET/CT examinations were performed before (PET1) and after (PET2) treatment to evaluate treatment response. A region of interest was placed over the primary lesion and metastatic lymph nodes within the thoracic cavity. PET parameters including change from PET1 to PET2 (Δ in %) were acquired: SUVmax, SUVpeak, MTV2.5, TLG, ΔSUVmax, ΔSUVpeak, ΔMTV and ΔTLG. Patient characteristics including staging, age, sex, LDH and response evaluation by RECIST were surveyed. Statistical analysis was done using Kaplan-Meier method and Cox regression analysis with respect to OS and PFS. RESULTS: The median follow-up was 9.6 months (2.5-80.5 months). 27 patients were LD and 32 were ED. Forty-six patients (78.0%) had died, and median OS was 8.6 months; 51 patients (86%) showed disease progression, and median PFS was 2.5 months. On univariate analysis, patients with ED, high interval change (ΔSUVmax and ΔSUVpeak) and low PET2 parameters showed longer OS and PFS. Multivariate analyses demonstrated that ΔSUVpeak (HR 2.6, P = 0.002) was an independent prognostic factors for OS, and MTV2.5 of PET2 (HR 2.8, P = 0.001), disease stage (HR 2.7, P = 0.003) and RECIST (HR 2.0, P = 0.023) were independent prognostic factors for PFS. CONCLUSIONS: Metabolic and volumetric PET parameters obtained from pre- and post-treatment FDG PET/CT examinations in patients with SCLC have significant prognostic information.

The Role of F-18 FDG PET/CT in Intrahepatic Cholangiocarcinoma.

PURPOSE: The aim of this study was to evaluate the diagnostic and prognostic role of metabolic parameters of FDG PET/CT in patients with intrahepatic cholangiocarcinoma (ICC). METHODS: From December 2008 to December 2013, 76 FDG PET/CT scans performed for initial staging of ICC in a single institution (57 male and 19 female; mean age 68 ± 9 years) were retrospectively reviewed. Patients with history of other known malignancy were excluded. Detection rates of regional lymph node and distant metastasis by FDG PET/CT were analyzed in comparison with conventional imaging modalities such as CT or MRI. Metabolic parameters including maximum, peak and mean standardized uptake values (SUVmax, SUVpeak, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), glucose corrected SUV (SUVgluc), and glucose corrected TLG (TLGgluc) were measured for the primary tumor. Cut-off values for the metabolic parameters were calculated by ROC curve analysis, and used to dichotomize the patient groups. The overall survival time (OS) was calculated and compared using the Cox proportional hazard regression analysis. RESULTS: The median duration of follow-up period was 5.4 months (interquartile range: 1.45∼15.45). FDG PET/CT showed higher sensitivity than conventional imaging modalities in detection of regional node involvement (74.5 % vs. 61.8 %, p = 0.013). In six patients, distant metastasis was identified only by FDG PET/CT. The mean SUVmax, SUVpeak, SUVmean, MTV, and TLG for the primary tumor were 8.2 ± 3.1, 6.8 ± 2.5, 4.0 ± 0.8, 192.7 ± 360.5 cm3, and 823.7 ± 1615.4, respectively. Patients with higher (≥7.3, HR: 4.280, p = 0.001), higher SUVpeak (≥6.5, HR: 2.333, p = 0.020), higher SUVmean (≥3.9, HR: 2.799, p = 0.004), higher SUVgluc (≥8.1, HR: 2.648, p = 0.012), and higher TLGgluc (≥431.6, HR: 2.186, p = 0.030) showed significantly shorter survival time. By multivariate study, operability was an independent prognostic factor for longer survival (HR: 4.113, p = 0.005). CONCLUSION: FDG PET/CT is an important diagnostic imaging tool in the nodal staging and detection of distant metastasis in ICC patients. Metabolic parameters may have a significant role as prognostic factors in patients with ICC.