Purpose: To support the phase I trial for toxicity, biodistribution and pharmacokinetics of intra-peritoneal (IP) 212Pb-TCMC-trastuzumab in patients with HER-2 expressing malignancy. A whole body gamma camera imaging method was developed for estimating amount of 212Pb-TCMC-trastuzumab left in the peritoneal cavity. Methods: 212Pb decays to 212Bi via beta emission. 212Bi emits an alpha particle at an average of 6.1 MeV. The 238.6 keV gamma ray with a 43.6% yield can be exploited for imaging. Initial phantom was made of saline bags with 212Pb. Images were collected for 238.6 keV with a medium energy general purpose collimator. There are other high energy gamma emissions (e.g. 511keV, 8%; 583 keV, 31%) that penetrate the septae of the collimator and contribute scatter into 238.6 keV. An upper scatter window was used for scatter correction for these high energy gammas. Results: A small source containing 212Pb can be easily visualized. Scatter correction on images of a small 212Pb source resulted in a ∼50% reduction in the full width at tenth maximum (FWTM), while change in full width at half maximum (FWHM) was <10%. For photopeak images, substantial scatter around phantom source extended to > 5 cm outside; scatter correction improved image contrast by removing this scatter around the sources. Patient imaging, in the 1st cohort (n=3) showed little redistribution of 212Pb-TCMC-trastuzumab out of the peritoneal cavity. Compared to the early post-treatment images, the 18-hour post-injection images illustrated the shift to more uniform anterior/posterior abdominal distribution and the loss of intensity due to radioactive decay. Conclusion: Use of medium energy collimator, 15% width of 238.6 keV photopeak, and a 7.5% upper scatter window is adequate for quantification of 212Pb radioactivity inside peritoneal cavity for alpha radioimmunotherapy of ovarian cancer. Research Support: AREVA Med, NIH 1UL1RR025777-01

Purpose: Study distribution, pharmacokinetics, and safety of intraperitoneal (IP) 212Pb-TCMC-trastuzumab in patients with HER-2-expressing malignancy. Experimental Design: IP 212Pb-TCMC-trastuzumab was delivered, after 4 mg/kg intravenous (IV) trastuzumab, to 3 patients with HER-2-expressing cancer who had failed standard therapies. Patients were monitored for toxicity and pharmacokinetics/dosimetry parameters. Results: Imaging studies after 0.2 mCi/m2 (7.4 MBq/m2) show little redistribution out of the peritoneal cavity and no significant uptake in major organs. Peak blood level of the radiolabeled antibody, determined by decay corrected counts, was <23% injected dose at 63 hours; maximum blood radioactivity concentration was 6.3nCi/mL at 18 hours. Cumulative urinary excretion was ≤6% in 2.3 half-lives. The maximum external exposure rate immediately post-infusion at skin contact over the abdomen averaged 7.67 mR/h and dropped to 0.67 mR/h by 24 hours. The exposure rates at the other positions monitored (axilla, chest, and femur) decreased as a function of distance from the abdomen. The data points correlate closely with 212Pb physical decay (T1/2=10.6 hours). Follow-up >6 months showed no evidence of agent-related toxicity. Conclusions: Pharmacokinetics and imaging after 0.2 mCi/m2 IP 212Pb-TCMC-trastuzumab in patients with HER-2-expressing malignancy showed minimal distribution outside the peritoneal cavity, ≤6% urinary excretion, and good tolerance.

This paper overviews recent advances in the JBluIce-EPICS open-source control system designed at the macromolecular crystallography beamlines of the National Institute of General Medical Sciences and National Cancer Institute at the Advanced Photon Source (GM/CA@APS). We discuss some technical highlights of this system distinguishing it from the competition, such as reduction of software layers to only two, possibility to operate JBluIce in parallel with other beamline controls, plugin-enabled architecture where the plugins can be written in any programming language, and utilization of the whole power of the Java integrated development environment in the Graphical User Interface. Then, we demonstrate how these highlights help to make JBluIce fast, easily adaptable to new beamline developments, and intuitive for users. In particular, we discuss several recent additions to the system including a bridge between crystal rastering and data collection, automatic detection of raster polygons from optical crystal centering, background data processing, and a pathway to a fully automated pipeline from crystal screening to solving crystal structure.

Purpose/Objective(s): To study the clinical effects, biodistribution, and pharmacokinetics of intra-peritoneal (IP) Pb-TCMC-trastuzumab in patients with HER-2 expressing malignancy who have failed standard therapies. Materials/Methods: IP Pb-TCMC-trastuzumab was delivered IP 6 months of first cohort showed no evidence of agent-related toxicity. Patients treated at higher dose level show a similar proportion of body counts, at rates commensurate with increased administered dose. These patients continue under follow-up. Conclusions: After confirmation of safety and expected distribution in monkeys, IP Pb-TCMC-trastuzumab treatment progressed to patients with peritoneal carcinomatosis. Pharmacokinetics and imaging showed minimal distribution outside the peritoneal cavity with little detectable organ uptake, 6 months in first group. Acknowledgment: This research was supported by ArevaMed and NIH CCTS grant 1UL1RR025777. Author Disclosure: R.F. Meredith: None. J. Torgue: None. M.T. Azure: None. S. Shen: None. E. Banaga: None. R. Carlisle: None. P. Bunch: None. D. Yoder: None. R. Alvarez: None.

597 Objectives To assess the variability in HIDA protocols across the state of Alabama. Cholescintigraphy interpretation can be affected by various factors including patient preparation and protocols utilized. Published SNM guidelines do not provide clear cut normal values for ejection fractions and offer choices for CCK infusion parameters. Results of many trials suggest longer infusion methods may be more accurate than slow hand injections. There is a need for updated standardized recommendations and translation of optimized techniques needs to be seen more widely in mainstream use. Methods 51 Nuclear Medicine departments in hospitals across the state of Alabama were surveyed by phone about various aspects of HIDA scan. Survey questions included, duration of fasting status and opiate withhold, requirements for Cholecystokinin (CCK) pretreatment, stimulation methods to assess gall bladder ejection fraction, duration and technique of CCK administration, normal values of gallbladder ejection fraction (GBEF) and procedures utilized if gallbladder non visualized. Results There is wide variability in patient preparation and HIDA scan protocols across hospitals in the state of Alabama, most notably with, CCK pretreatment, its duration of administration and the normal GBEF values. Only 5 of the 51 hospitals pretreated with CCK if the patient was fasting for > 24 hours whereas 10 hospitals hand injected CCK in less than 3 minutes. The others used hand injection or CCK infusion over variable time periods. The normal GBEF values varied between 30 and 50% respectively. Conclusions A wide variability in the HIDA protocol was noted across the state of Alabama which likely reflects patterns elsewhere. This may affect the diagnostic accuracy of cholescintigraphy