Comparison between internalizing anti-HER2 mAbs and non-internalizing anti-CEA mAbs in alpha-radioimmunotherapy of small volume peritoneal carcinomatosis using 212Pb.

BACKGROUND AND PURPOSE: We assessed the contribution of antibody internalization in the efficacy and toxicity of intraperitoneal α-radioimmunotherapy (RIT) of small volume carcinomatosis using (212)Pb-labeled monoclonal antibodies (mAbs) that target HER2 (internalizing) or CEA (non-internalizing) receptors. MATERIALS AND METHODS: Athymic nude mice bearing 2-3 mm intraperitoneal tumor xenografts were intraperitoneally injected with similar activities (370, 740 and 1480 kBq; 37 MBq/mg) of (212)Pb-labeled 35A7 (anti-CEA), trastuzumab (anti-HER2) or PX (non-specific) mAbs, or with equivalent amounts of unlabeled mAbs, or with NaCl. Tumor volume was monitored by bioluminescence and survival was reported. Hematologic toxicity and body weight were assessed. Biodistribution of (212)Pb-labeled mAbs and absorbed dose-effect relationships using MIRD formalism were established. RESULTS: Transient hematological toxicity, as revealed by white blood cells and platelets numbering, was reported in mice treated with the highest activities of (212)Pb-labeled mAbs. The median survival (MS) was significantly higher in mice injected with 1.48 MBq of (212)Pb-35A7 (non-internalizing mAbs) (MS = 94 days) than in animals treated with the same activity of (212)Pb-PX mAbs or with NaCl (MS = 18 days). MS was even not reached after 130 days when follow-up was discontinued in mice treated with 1.48 MBq of (212)Pb-trastuzumab. The later efficacy was unexpected since final absorbed dose resulting from injection of 1.48 MBq, was higher for (212)Pb-35A7 (35.5 Gy) than for (212)Pb-trastuzumab (27.6 Gy). These results also highlight the lack of absorbed dose-effect relationship when mean absorbed dose was calculated using MIRD formalism and the requirement to perform small-scale dosimetry. CONCLUSIONS: These data indicate that it might be an advantage of using internalizing anti-HER2 compared with non-internalizing anti-CEA (212)Pb-labeled mAbs in the therapy of small volume xenograft tumors. They support clinical investigations of (212)Pb-mAbs RIT as an adjuvant treatment after cytoreductive surgery in patients with peritoneal carcinomatosis.

Patient-specific dosimetry in radionuclide therapy.

This study presents an attempt to compare individualised palliative treatment absorbed doses, by planar images data and Monte Carlo simulation, in two in vivo treatment cases, one of bone metastases and the other of liver lesions. Medical Internal Radiation Dose schema was employed to estimate the absorbed doses. Radiopharmaceutical volume distributions and absorbed doses in the lesions as well as in critical organs were also calculated by Monte Carlo simulation. Individualised planar data calculations remain the method of choice in internal dosimetry in nuclear medicine, but with the disadvantage of attenuation and scatter corrections lack and organ overlay. The overall error is about 7 % for planar data calculations compared with that using Monte Carlo simulation. Patient-specific three-dimensional dosimetric calculations using single-photon emission computed tomography with a parallel computed tomography study is proposed as an accurate internal dosimetry with the additional use of dose-volume histograms, which express dose distributions in cases with obvious inhomogeneity.

Alternative production methods to face global molybdenum-99 supply shortage.

The sleeping giant of molybdenum-99 ((99)Mo) production is grinding to a halt and the world is wondering how this happened. Fewer than 10 reactors in the world are capable of producing radio nuclides for medicine; approximately 50% of the world's supply of raw material comes from National Research Universal (NRU) reactor in Canada. Many of these reactors, like the NRU, are old and aging. No one of these reactors, and probably not even all of them in combination, can replace the production of NRU. As the healthcare industry faces an aging population and the demand for diagnostic services using (99m)Tc continues to rise, the need for a consistent, reliable supply of (99)Mo has become increasingly important, so alternative methods to produce (99)Mo or even directly (99m)Tc had to be considered to avoid a supply shortage in the coming years. This need guides to the production of (99)Mo by replacing the Highly Enriched Uranium (HEU) target in a nuclear reactor with Low Enriched Uranium (LEU) and furthermore to the use of accelerators for manufacturing (99)Mo or for directly producing (99m)Tc.