ABSTRACT
INTRODUCTION: (131)I-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK) and safety profiles of (131)I-CLR1404. METHODS: Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of (131)I-CLR1404. Whole body planar nuclear medicine scans were performed at 15-35 minutes, 4-6, 18-24, 48, 72, 144 hours, and 14 days post injection. Optional single photon emission computed tomography imaging was performed on two patients 6 days post injection. Clinical laboratory parameters were evaluated in blood and urine. Plasma PK was evaluated on (127)I-CLR1404 mass measurements. To evaluate renal clearance of (131)I-CLR1404, urine was collected for 14 days post injection. Absorbed dose estimates for target organs were determined using the RADAR method with OLINDA/EXM software. RESULTS: Single administrations of 370 MBq of (131)I-CLR1404 were well tolerated by all subjects. No severe adverse events were reported and no adverse event was dose-limiting. Plasma (127)I-CLR1404 concentrations declined in a bi-exponential manner with a mean t½ value of 822 hours. Mean Cmax and AUC(0-t) values were 72.2 ng/mL and 15753 ng ⢠hr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow. CONCLUSIONS: Preliminary data suggest that (131)I-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent. TRIAL REGISTRATION: ClinicalTrials.gov NCT00925275.
Subject(s)
Iodobenzenes/pharmacology , Iodobenzenes/therapeutic use , Neoplasms/pathology , Neoplasms/radiotherapy , Phospholipid Ethers/pharmacology , Phospholipid Ethers/therapeutic use , Aged , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Neoplasm Staging , Neoplasms/diagnosis , Radiometry , Tissue Distribution , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed , Whole Body ImagingABSTRACT
Louisville and Jefferson County, Kentucky has a comprehensive program for hazardous materials control based on realistic regulation and outstanding cooperation between industry and local gevernment agencies. The success of the program is more noteworthy because the area of 700,000 population covered involves the major city of Louisville, a heavily populated unincorporated County area, and 93 small incorporated cities. The political support for the program was generated after a series of hazardous materials incidents including a runsway chlorine gas barge, a sewer explosion and chemical contamination of the communities major wastewater treatment plant.This paper will discuss the elements of the program in Louisville and Jefferson County and the cooperative process used that assured the sucess.(AU)
