RT Journal Article
SR Electronic
T1 Use of Polyglutamic Acids to Reduce Uptake of Radiometal-Labeled Minigastrin in the Kidneys
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1012
OP 1015
VO 46
IS 6
A1 Martin Béhé
A1 Gerald Kluge
A1 Wolfgang Becker
A1 Martin Gotthardt
A1 Thomas M. Behr
YR 2005
UL http://jnm.snmjournals.org/content/46/6/1012.abstract
AB Uptake of radiolabeled peptides in the kidneys may obscure abdominal tumors in radiopeptide scintigraphy. This problem is much more pronounced in peptide receptor radionuclide therapy (i.e., radiopeptide therapy), possibly leading to renal damage or even failure. Cationic peptide uptake in the kidneys can be reduced by the application of cationic amino acids, such as lysine or arginine. The aim of this study was to develop a suitable method to reduce anionic peptide uptake in the kidneys. 111In-Diethylenetriaminepentaacetic acid dGlu1-minigastrin (111In-DTPA-dGlu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) was chosen as a model compound with a sequence of 6 negatively charged glutamic acids in a chain and an additional aspartic acid. Methods: TT (human medullary carcinoma cells)-bearing nu/nu mice of the Institute of Cancer Research genotype received intraperitoneal injections of different chain lengths and weights of glutamic acids, aspartic acids, and derivatives of glutamic acids. Uptake in tumors and organs was determined and compared with the values for untreated control mice. Results: Accretion of 111In-DTPA-dGlu1-minigastrin in the kidneys could be reduced by up to 90%. The uptake values for all other organs and the tumors were not affected. These results were obtained with a chain of 5 or more glutamic acids, whereas uptake in kidneys was affected not at all or only slightly with poly-d-glutamic or polyaspartic acids and with Glux (x = 1–4). Conclusion: These studies indicated a specific blocking of uptake by Glu5 sequences in the kidneys. Application of polyglutamic acids is a new, successful method of reducing uptake of negatively charged peptides in the kidneys during radiopeptide therapy.