Pharmacokinetics of Genetically Engineered Antibody Forms Using Positron Emission Tomography

Steven M. Larson, M.D. Nai-Kong Cheung, M.D., Ph.D.

Steven M. Larson/Sloan-Kettering Institute for Cancer Research (United States)

关键词: Monoclonal Antibodies;    Novel Radiolabeling Strategies;    Radioisotopes;    Multi-Step Targeting;    Dosimetry;   

DOI  :  10.2172/828873
RP-ID  :  NONE
RP-ID  :  FG02-95ER62039
RP-ID  :  828873

美国|英语

来源: UNT Digital Library

【 摘 要 】

In the last grant period we have focused on multi-step targeting methodologies (MST), as a method for delivery of high dose to the tumor, with low dose to the bone marrow. We have explored uptake in colorectal, pancreatic and prostate cancer, using an special preparation, developed in collaboration with NeoRex A high tumor/bone marrow ratio is clearly achieved with MST, but with a cost, namely the higher dose to normal kidney. For this reason, we have in particular, (a) looked dosimetry for both tumor and normal organ, and especially renal dosimetry, which appears to be the target organ, for Y-90. (b) In parallel with this we have explored the dosimetry of very high dose rate radionuclides, including Holmium-166. (c) In addition, with NaiKong Cheung, we have developed a new MST construct based on the anti-GD2 targeting 5F11; (d) we have successfully completed development of s-factor tables for mice. In summary, renal dosimetry is dominated by about 4-5% of the injected dose being held long-term in the renal cortex, probably in the proximal tubule, due to the universal uptake of small proteins. This appears to be a function of a biotynlated protein binding of the strept-avidin construct, to HSP70. This cortical uptake has caused us to reconsider renal dosimetry as a whole, with the smaller mass of the cortex, rather than the whole kidney, as the target organ. These insights into dosimetry will be of great importance as MST, becomes more common in clinical practice.