A kit formulated under good manufacturing practices for labeling human epidermal growth factor with 111In for radiotherapeutic applications.

UNLABELLED: Our goal was to design and manufacture a kit under good manufacturing practices (GMP) for the preparation of (111)In-DTPA-hEGF Injection, a novel targeted radiotherapeutic agent for advanced epidermal growth factor receptor (EGFR)-positive breast cancer. METHODS: Human EGF (hEGF) was derivatized with diethylenetriaminepentaacetic acid (DTPA) and then purified by size-exclusion chromatography and ultrafiltration. Kits were prepared by dispensing 0.25 mg (1 mL) of DTPA-hEGF in 1 mol/L sodium acetate buffer [pH 6.0] into single-dose glass vials. Raw materials were pharmacopoieal or reagent grade according to the American Chemical Society and were tested for identity and purity. Kits were tested for protein concentration, purity and homogeneity (sodium dodecyl sulfate polyacrylamide gel electrophoresis and size-exclusion high-performance liquid chromatography), pH, clarity and color, volume, DTPA substitution, labeling efficiency, receptor binding to MDA-MB-468 human breast cancer cells, and sterility and apyrogenicity. (111)In-DTPA-hEGF Injection was tested for pH, radionuclidic and radiochemical purity, clarity and color, and sterility and apyrogenicity. RESULTS: Four lots of kits and 8 lots of (111)In-DTPA-hEGF Injection passed all quality specifications. The labeling efficiency was 94%-99% with 115-773 MBq (111)In chloride added to a single kit. (111)In-DTPA-hEGF exhibited preserved receptor binding against MDA-MB-468 cells (affinity constant [K(a)], 0.9-1.1 x 10(7) L/mol; maximum number of binding sites per cell [B(max)], 1.1-2.2 x 10(6) sites per cell). In addition, labeling of aliquots of the kit suggested that a single vial could be labeled with up to 3,083 MBq (111)In while maintaining a radiochemical purity of >90%. Kits were stable for >90 d and (111)In-DTPA-hEGF Injection was stable for >24 h stored at 4 degrees C. CONCLUSION: The kit formulation is suitable for preparing (111)In-DTPA-hEGF Injection for a phase I clinical trial in patients with advanced EGFR-positive breast cancer. Establishment of the GMP processes for (111)In-DTPA-hEGF Injection provides a useful example of manufacturing biotechnology-based investigational radiopharmaceuticals in an academic environment for early phase I clinical trials.

Calculation of 18F, 99mTc, 111In and 123I calibration factor using the penelope ionization chamber simulation method.

A new method using the Monte Carlo code PENELOPE for ionization chamber simulation has already been successfully used for calculating calibration factors needed for the measurements of radionuclides with photon emission (2003, Appl. Radiat. Isot., to be published). This work has been continued at (Laboratoire National Henri Becquerel) in order to calculate the calibration factors for radionuclides with short half-lives used in medical services. Activity measurements of 18F, 99mTc,111In and 123I using the calculated calibration factors were obtained with standard uncertainties equal to 0.6% for 18F, 99mTc and 1.5% for 111In and 123I.