Measurement of preoperative lobar lung function with computed tomography ventilation imaging: progress towards rapid stratification of lung cancer lobectomy patients with abnormal lung function.

OBJECTIVES: In lung cancer preoperative evaluation, functional lung imaging is commonly used to assess lobar function. Computed tomography ventilation (CT-V) imaging is an emerging lung function imaging modality. We compared CT-V imaging assessment of lobar function and its prediction of postoperative lung function to that achieved by (i) positron emission tomography ventilation (PET-V) imaging and (ii) the standard anatomical segment counting (ASC) method. We hypothesized (i) that CT-V and PET-V have similar relative lobar function and (ii) that functional imaging and anatomic assessment (ASC) yield different predicted postoperative (ppo) lung function and therefore could change clinical management. METHODS: In this proof-of-concept study, 11 patients were subjected to pulmonary function tests, CT-V and PET-V imaging. The Bland-Altman plot, Pearson's correlation and linear regression analysis were used to assess the agreement between the CT-V-, PET-V- and ASC-based quantification of lobar function and in the ppo lung function. RESULTS: CT-V and PET-V imaging demonstrated strong correlations in quantifying relative lobar function (r = 0.96; P < 0.001). A Wilcoxon-signed rank test showed no significant difference in the lobar function estimates between the two imaging modalities (P = 0.83). The Bland-Altman plot also showed no significant differences. The correlation between ASC-based lobar function estimates with ventilation imaging was low, r < 0.45; however, the predictions of postoperative lung function correlated strongly between all three methods. CONCLUSIONS: The assessment of lobar function from CT-V imaging correlated strongly with PET-V imaging, but had low correlations with ASC. CT-V imaging may be a useful alternative method in preoperative evaluation for lung cancer patients.

Lutetium-177 DOTATATE Production with an Automated Radiopharmaceutical Synthesis System.

OBJECTIVES: Peptide Receptor Radionuclide Therapy (PRRT) with yttrium-90 ((90)Y) and lutetium-177 ((177)Lu)-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system. METHODS: All syntheses were carried out using the Eckert & Ziegler Eurotope's Modular-Lab Pharm Tracer® automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany). Sterile, GMP-certified, no-carrier added (NCA) (177)Lu was used with GMP-certified peptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLC-SG and HPLC methods. RESULTS: A total of 17 [(177)Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [(177)Lu]-DOTATATE produced by each synthesis varied between 10-40 GBq and was dependant on the number of patients being treated on a given day. Thirteen individuals received a total of 37 individual treatment administrations in this period. There were no issues and failures with the system or the synthesis cassettes. The average radiochemical purity as determined by ITLC was above 99% (99.8 ± 0.05%) and the average radiochemical purity as determined by HPLC technique was above 97% (97.3 ± 1.5%) for this period. CONCLUSIONS: The automated synthesis of [(177)Lu]-DOTATATE using Eckert & Ziegler Eurotope's Modular-Lab Pharm Tracer® system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE peptide benefiting from the use of NCA (177)Lu and almost negligible radiation exposure of the operators.

Gallium-68 DOTATATE Production with Automated PET Radiopharmaceutical Synthesis System: A Three Year Experience.

OBJECTIVES: Gallium-68 (Ga-68) is an ideal research and hospital-based PET radioisotope. Currently, the main form of Ga-68 radiopharmaceutical that is being synthesised in-house is Ga-68 conjugated with DOTA based derivatives. The development of automated synthesis systems has increased the reliability, reproducibility and safety of radiopharmaceutical productions. Here we report on our three year, 500 syntheses experience with an automated system for Ga-68 DOTATATE. METHODS: The automated synthesis system we use is divided into three parts of a) servomotor modules, b) single use sterile synthesis cassettes and, c) a computerised system that runs the modules. An audit trail is produced by the system as a requirement for GMP production. The required reagents and chemicals are made in-. The Germanium breakthrough is determined on a weekly basis. Production yields for each synthesis are calculated to monitor the performance and efficiency of the synthesis. The quality of the final product is assessed after each synthesis by ITLC-SG and HPLC methods. RESULTS: A total of 500 Ga-68 DOTATATE syntheses (>800 patient doses) were performed between March 2011 and February 2014. The average generator yield was 81.3±0.2% for 2011, 76.7±0.4% for 2012 and 75.0±0.3% for 2013. Ga-68 DOTATATE yields for 2011, 2012, and 2013 were 81.8±0.4%, 82.2±0.4% and 87.9±0.4%, respectively. These exceed the manufacturer's expected value of approximately 70%. Germanium breakthrough averaged 8.6×10(-6)% of total activity which is well below the recommended level of 0.001%. The average ITLC-measured radiochemical purity was above 98.5% and the average HPLC-measured radiochemical purity was above 99.5%. Although there were some system failures during synthesis, there were only eight occasions where the patient scans needed to be rescheduled. CONCLUSION: In our experience the automated synthesis system performs reliably with a relatively low incident of failures. Our system had a consistent and reliable Ga-68 DOTATATE output with high labelling efficiency and purity. There is minimal operator intervention and radiation exposure. The system is GMP-compliant and has low maintenance and acceptable running costs. This system together with the recommended (68)Ge/(68)Ga generator is well suited for use in a hospital-based radiopharmacy.

The use of molecular sieves to produce point sources of radioactivity.

We have used commercially available molecular sieves (zeolites) to adsorb radioactivity onto small (approximately 2.1 mm diameter) beads for use in various applications in nuclear medicine. Soaking the beads in [99mTc]-NaTcO4 solution of approximately 3 GBq ml(-1) for 1-2 min can produce point sources containing 3-6 MBq total. Radioactive uptake was strongly dependent on bead size. We have employed the sources for gamma camera uniformity and as point source markers for interactive identification of anatomical landmarks. Due to their small size (<< system spatial resolution), relatively high uptake and negligible scattering contribution they provide excellent devices with which to measure spatial resolution, detector uniformity and energy resolution. The molecular sieves are inexpensive and readily usable with both single photon and positron emitting radionuclides.