Ultra-fast liquid chromatography method coupled with ultraviolet detection to quantify dimethylsulfoxide, dimethylformamide and dimethylacetamide in short half-lives radiopharmaceuticals.

Radiolabelling with short half-lives radionuclides (e.g., fluorine-18 and carbon-11) must be as efficient and as fast as possible. Nucleophilic radiofluorinations and radiomethylations are conducted in polar aprotic solvents, such as dimethylsulfoxyde (DMSO), N,N-dimethylformamide (DMF) and N,N-dimethylacetamide (DMA), at high temperature. Those solvents are classified as toxic according to the ICH guidelines and must be evaluated in drug such as radiopharmaceuticals. Headspace gas chromatography is the standard method for the quantification of residual solvents but is not optimized for a rapid quantification of low vapor pressure solvents such as DMSO, DMF and DMA in radiopharmaceuticals. Direct injection gas chromatography is an interesting option without incubation step but the analysis run-time remains beyond 10 min long. In consequence, we developed a very simple ultra-high performance liquid chromatography method coupled with UV detection. Following the EMA requirements, we successfully validated a 3-min run-time analysis for quantification of three solvents in short half-lives radiopharmaceuticals. We currently use this method for the quality control of radiopharmaceuticals produced in our PET center.

Assessment of response to endocrine therapy using FDG PET/CT in metastatic breast cancer: a pilot study.

PURPOSE: The purpose of this pilot study was to assess whether outcome in metastatic or recurrent breast cancer patients is related to metabolic response to endocrine therapy determined by (18)F-FDG PET/CT. METHODS: The study group comprised 22 patients with breast cancer (age 58 ± 11 years, mean ± SD) who were scheduled to receive endocrine therapy. They were systematically assessed by PET/CT at baseline and after a mean of 10 ± 4 weeks for evaluation of response after induction. All patients demonstrated FDG-avid lesions on the baseline PET/CT scan. The metabolic response was assessed according to EORTC criteria and based on the mean difference in SUV(max) between the two PET/CT scans, and the patients were classified into four groups: complete or partial metabolic response, or stable or progressive metabolic disease (CMR, PMR, SMD and PMD, respectively). All patients were followed in our institution. RESULTS: Metastatic sites were localized in bone (n = 15), lymph nodes (n = 11), chest wall (n = 3), breast (n = 5), lung (n = 3), soft tissue (n = 1) and liver (n = 1). PMR was observed in 11 patients (50%), SMD in 5 (23%) and PMD in 6 (27%). The median progression-free survival (PFS) times were 20, 27 and 6 months in the PMR, SMD and PMD groups, respectively. PFS in the SMD group differed from that in the PMR and SMD groups (p < 0.0001). CONCLUSION: Metabolic response assessed by FDG PET/CT imaging in patients with metastatic breast cancer treated with endocrine therapy is predictive of the patients' PFS.

Application of an Environmental Monitoring to Assess the Practices and Control the Risk of Occupational Exposure to Cyclophosphamide in Two Sites of a French Comprehensive Cancer Center.

OBJECTIVES: The risk of chronic exposure to antineoplastic agents in hospitals, mainly by skin contact with contaminated surfaces, is well established. The aim of this study was to assess indirectly the risk of occupational exposure to antineoplastics drugs at two hospitals by using an environmental monitoring, and to suggest ways of improving the exposure to healthcare workers. METHODS: An observational study of care practices on both sites was carried out. A wipe sampling campaign was then designed to study environmental contamination throughout the chemotherapy process: receipt, storage, compounding, transport, administration, and elimination areas. Samples were analyzed by a validated LC-MS/MS method allowing trace quantification of cyclophosphamide. A guidance 'safe value' of 0.10 ng/cm2 was considered. RESULTS: A total of 293 samples were analyzed, of which 58% were found to be positive. In the compounding units, the drug vials were contaminated before [range = (non-quantifiable [NQ]-0.71) ng/cm2] and after cleaning procedure [(NQ-0.62) ng/cm2], particularly when the flip-off lid was removed during cleaning. The contamination found on manual preparations was operator-dependent: [non-detectable (ND)-3.51] ng/cm2 on infusion bag surfaces; (780.61-24 698.98) ng/cm2 on medication ports. In the case of automated preparations, the average contamination was higher on infusion bag surfaces [(2.43-36.86) ng/cm2] and lower on medication ports [(0.43-7.65) ng/cm2] than manual preparations. Contamination of the analytical control area was also highlighted. In the daily care unit, the contamination was located near the infusion area (armchairs, infusion stands, floor, and patient toilets), and varied somewhat between the two sites, especially on the floor with (0.46-27.32) compared to (ND-0.18) ng/cm2. We did not detect contamination on the transport boxes, on the door handles or in the disposal areas. CONCLUSIONS: The variability of contamination observed between the two sites can be explained in part by the difference in routine practices, especially training of the staff, and cleaning procedures. Findings were communicated to healthcare workers, and news interventions were implemented based on wipe sampling results. This study demonstrated a method for routine environmental monitoring and worker education as a strategy to reduce occupational exposure.

Single photon emission tomography/computed tomography (SPET/CT) and positron emission tomography/computed tomography (PET/CT) to image cancer.

Hybrid systems associating the sharpness of anatomic images coming from computed tomography (CT) and radionuclide functional imaging (SPET or PET) are opening a new era in oncology. This multimodal imaging method is now routinely used for the diagnosis, extent, follow up, treatment response and detection of occult disease in different types of malignancies with a significant impact on the treatment strategy leading for a change for more than 68% of all investigated patients.

Single radio UHPLC analysis for the quality control of technetium-99m radiolabelled radiopharmaceuticals.

The radiochemical purity (RCP) determination of radiopharmaceuticals is routinely done with radio-thin layer chromatography (r-TLC). These methods are usually transposed and adjusted from the summary product characteristics without any analytical validation. The r-TLC method is simple but manually-performed steps could lead to RCP misinterpretation. To increase the sensitivity, radio ultra-high performance liquid chromatography (r-UHPLC) can be used. In this study, an r-UHPLC method had been validated and compared to the r-TLC method. Hydrolyzed-reduced technetium had also been studied.

Pharmacokinetic Analysis of [18F]FAZA Dynamic PET Imaging Acquisitions for Highlighting Sacrum Tumor Profiles.

A patient enrolled in a clinical trial (NCT02802969) with suspicion of chordoma underwent an [F]FAZA PET/CT, a radiolabeled nitroimidazole analog of hypoxia PET imaging. The patient's images showed a different tumor profile compared to those observed in other hypoxic or nonhypoxic chordoma patients. The motivation for using [F]FAZA pharmacokinetic imaging was to compare this profile with histologically confirmed cases of chordoma. Through visual imaging and quantification of blood and tumor time-activity curves, we excluded the hypothesis that it was a chordoma, diagnosing a paraganglioma.

Validation of an ergonomic method to withdraw [99mTc] radiopharmaceuticals.

The main objective of the present work was to ensure quality of radiopharmaceuticals syringes withdrawn with a "Spinal needle/obturator In-Stopper" system. Methods: Visual examinations and physicochemical tests are performed at T0 and T+4h for [99mTc]albumin nanocolloid and T+7h for [99mTc]eluate, [99mTc] HydroxyMethylene DiPhosphonate and [99mTc]Human Serum Albumin. Microbiological validation was performed according to European pharmacopoeia. Fingertip radiation exposure was evaluated to confirm the safety of the system. Results: Results show stable visual and physicochemical properties. The integrity of the connector was not affected after 30 punctures (no cores). No microbiological contamination was found on tested syringes. Conclusion: The system could be used 30 times. The stability of syringes drawing with this method is guaranteed up to 4 hours for [99mTc]albumin nanocolloid and 7 hours for [99mTc]eluate, [99mTc]HydroxyMethylene DisPhosphonate and [99mTc]Human serum albumin.

Breast cancer recurrence diagnosis suspected on tumor marker rising: value of whole-body 18FDG-PET/CT imaging and impact on patient management.

BACKGROUND: Breast cancer recurrence is often suspected on tumor marker rising in asymptomatic patients. The value of fluorine-18 fluorodeoxyglucose (18FDG)-positron emission tomography/computed tomography (PET/CT) imaging to detect recurrence and its subsequent impact on patient management were retrospectively assessed. METHODS: PET/CT scans were performed on 228 asymptomatic patients (mean, 60.8 years; range, 30-91 years) presenting with rising CA 15-3 and/or CEA serum levels. RESULTS: PET/CT scans were positive in 181 patients (79.5%) and normal in 47 patients, whereas 187 true recurrences were diagnosed. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT imaging for detection of breast cancer recurrence were 93.6%, 85.4%, 96.7%, 74.5%, and 92.1%, respectively. When compared with the standard workup available in 67 patients, PET/CT imaging had a higher sensitivity and accuracy (94.5% vs 33% and 94% vs 48%, respectively). Recurrences were confirmed by pathology, conventional imaging techniques, or radiological and clinical follow-up beyond 1 year (mean, 34 months; range, 12-67 years) in 32, 130, and 25 patients, respectively. The diagnosis of recurrence led to a treatment modification in 123 patients (54%). CONCLUSIONS: 18FDG-PET/CT imaging is an efficient technique to detect breast cancer recurrence suspected on tumor marker rising in asymptomatic patients. It may thus contribute to improve patient management, providing an earlier diagnosis with complete whole-body staging as a "one-stop shop" procedure.