131I-rituximab: relationship between immunoreactivity and specific activity

As part of a search for optimal conditions for radioimmunotherapy of lymphoma, rituximab was labeled with 2 different specific activities of 131I and immunoreactivity was comparatively measured. METHODS: Labeling was performed with chloramine T using as starting conditions 185 MBq of 131I per 1 mg and per 5 mg of antibody for labelings A and B, respectively. Six comparative labelings were performed over a period of 10 mo with similar efficacy and purified by anion-exchange chromatography. Immunoreactivity was determined immediately after labeling in parallel assays using different concentrations of fresh Raji and Daudi cells. Results were compared at maximal observed specific binding on 10(7) cells and after extrapolation to infinite antigen excess. A statistical analysis was performed to predict the frequency of radiolabeled mono- and polyiodinated antibodies: First, a gaussian distribution predicted the number of iodine atoms per antibody in labelings A and B, respectively; then, the radiolabeling probability was developed according to the Newton binome. RESULTS: Final radiochemical purity was >98.4% for all labelings. The final mean specific activities were 169.7 MBq/mg and 32.8 MBq/mg, corresponding to 0.87 and 0.17 iodine atoms per antibody in labelings A and B, respectively. Labeling B showed a significantly higher immunoreactivity than did labeling A, the mean relative increase in binding being > or =28% for both Raji cells and Daudi cells. The predictive statistical analysis indicated that 57.3% and 15.4% of radiolabeled antibodies in labelings A and B, respectively, were polyiodinated. CONCLUSION: The low specific activity of 131I-rituximab allowed preservation of a high immunoreactivity and correlated with the prediction of a low percentage of polyiodinated radiolabeled antibodies

Preclinical Auger and gamma radiation dosimetry for fluorodeoxyuridine-enhanced tumour proliferation scintigraphy with [123I]iododeoxyuridine

Animal experiments have shown that short blocking of thymidine (dThd) synthesis with fluorodeoxyuridine (FdUrd) results in significantly increased DNA incorporation of [(125)I]iododeoxyuridine ([(125)I]IdUrd) in tumour and rapidly cycling tissues. Based on these results, we give an Auger and gamma radiation dosimetry estimate for a scintigraphy study in glioblastoma patients using [(123)I]IdUrd. The Auger radiation dosimetry calculated for patients is based on measurement of DNA-incorporated [(125)I]IdUrd in rapidly dividing tissues in nude mice xenografted with human glioblastoma. Further data obtained 0.5, 6 and 24 h after injection of [(125)I]IdUrd allowed calculation of the additional gamma radiation exposure using MIRDOSE3.1. High gradients of radioactivity concentration between dividing and non-dividing tissues were observed 6 and 24 h after injection of [(125)I]IdUrd combined with FdUrd pretreatment. While the estimated Auger radiation absorbed doses of [(123)I]IdUrd in six rapidly cycling normal tissues in patients are low, the equivalent doses become significant with application of the recommended preliminary radiation weighting factor (W(R)) of 20 for stochastic effects of DNA-associated Auger radiation. Using the latter W(R), extrapolation of the animal results to the proposed patient injection with 300 MBq [(123)I]IdUrd combined with FdUrd pretreatment indicates that the effective dose will be 5.42 mSv, including 1.67 mSv from Auger and 3.75 mSv from gamma radiation. The predicted Auger radiation effective dose for patients undergoing [(123)I]IdUrd scintigraphy will be significant if the enhancement of DNA incorporation that is achieved by means of FdUrd pretreatment is similar to that obtained in animals

Radiolabeled neurotensin analog, 99mTc-NT-XI, evaluated in ductal pancreatic adenocarcinoma patients

The study aim was to assess the safety, biodistribution, tissue kinetics, and tumor uptake of the (99m)Tc-labeled neurotensin (NT) analog NT-XI. METHODS: Four patients presenting ductal pancreatic adenocarcinoma were studied with (99m)Tc-NT-XI. Patients were followed by scintigraphy up to 4 h and by continued blood and urinary sampling until surgery 18-22 h after injection. Surgical tissue samples were analyzed for radioactivity uptake and NT receptor expression. RESULTS: No side effects were observed on injection of (99m)Tc-NT-XI. Blood biologic half-lives alpha and beta were 35 min (range, 17-62 min) and 230 min (range, 107-383 min), respectively. Repeated whole-body scintigraphy performed in 2 patients showed a single exponential decrease of whole-body activity with half-lives of 101 and 232 min. Tracer elimination was mainly renal, with 92% and 98% of activity counted in urine in the first 20 h. Kidney, liver, spleen, and bone marrow activity uptake was observed in all patients. Tumor was not visualized in the first 3 patients but could be localized by tomoscintigraphy in the pancreas head region of patient 4. In vitro tissue analysis showed high expression of NT receptor in the tumor of patient 4, correlated with the highest tumor radioactivity uptake and the highest tumor-to-fat radioactivity ratio. In vitro receptor expression was also positive in a second patient having a tumor characterized by very low cellularity; however, the remaining 2 tumors lacked NT receptor expression. CONCLUSION: Injection of (99m)Tc-NT-XI was well tolerated. The in vivo tumor uptake appeared specific as it was observed in the 1 patient with a pancreatic tumor that expressed high amounts of NT receptor. The results are compatible with preclinical animal results and in favor of further development of radiolabeled NT analogs for diagnosis or therapy of cancer