HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by García-Garayoa, E. Articles by Schubiger, P. A. Search for Related Content PubMed PubMed Citation Articles by García-Garayoa, E. Articles by Schubiger, P. A.

Preclinical Evaluation of a New, Stabilized Neurotensin(8–13) Pseudopeptide Radiolabeled with ^99mTc

¹ Center for Radiopharmaceutical Science, Paul Scherrer Institute, Villigen, Switzerland
² Department of Organic Chemistry, Vrije Universiteit Brussel, Brussels, Belgium

View larger version (10K): [in a new window]   FIGURE 1. Sequence of NT-VIII (bottom), compared with NT(7–13) (top). Atoms in boldface represent ligands for metal complex formation with 99mTc(CO)3+ and natRe(CO)3+. nat = natural isotopes 185/187.

View larger version (18K): [in a new window]   FIGURE 2. Degradation of NT-VIII in vitro after incubation at 37°C, compared with nonstabilized analog NT-II and monostabilized analog NT-VI (25). Data represent mean of 2 experiments.

View larger version (19K): [in a new window]   FIGURE 3. Binding of analog NT-VIII to human colon adenocarcinoma HT-29 cells. (A) Inhibition of specific binding of 125I-NT by increasing concentrations of NT(8–13) and NT-VIII. (B) Saturation curve for 99mTc(CO)3NT-VIII in absence (, total binding) or presence (, nonspecific binding) of 1 µmol/L unlabeled NT(8–13) for 1 h at 37°C. Specific binding (•) was calculated as difference between total and nonspecific binding. Small graph shows Scatchard analysis of data. Each point is mean of triplicate determinations from representative experiment of total of 3 separate experiments.

View larger version (18K): [in a new window]   FIGURE 4. Time course internalization of 99mTc(CO)3NT-VIII in HT-29 cells at 37°C with () and without (•) preincubation at 4°C. Data are percentage of acid-resistant activity related to total activity in cells (surface-bound and internalized). Each point represents mean of 2–3 experiments in triplicate.

View larger version (20K): [in a new window]   FIGURE 5. Time-dependent downregulation and subsequent reappearance of NT receptors in HT-29 cells after incubation with NT(8–13) (•) and NT-VIII () at concentration of 3 nmol/L. Results are percentage of maximal binding in control cells and represent mean ± SD of 2–3 experiments in triplicate.

View larger version (20K): [in a new window]   FIGURE 6. Biodistribution in nude mice bearing HT-29 tumor xenografts at different time points after intravenous injection of 99mTc(CO)3NT-VIII (3.5–4 MBq/mouse). Data are %ID/g by reference to total injected dose. Each bar represents mean ± SD of 3–6 animals.

View larger version (45K): [in a new window]   FIGURE 7. Scintigraphy image of mouse bearing tumor xenografts 1.5 h after intravenous injection of 99mTc(CO)3NT-VIII (3.5–4 MBq) shows human colon adenocarcinoma HT-29 xenograft (A), liver (B), kidneys (C), and human prostate carcinoma PC-3 xenograft (D). Tumors were induced by subcutaneous injection of 8 x 106 cells of each type 10 d before assay.

View larger version (14K): [in a new window]   FIGURE 8. Biodistribution of 99mTc(CO)3NT-VIII (3.5–4 MBq/mouse) at 1.5 h after injection after blockade of NTR1. Data are %ID/g by reference to total dose injected and represent mean ± SD (n = 3–6). Displacer = (NHis)Ac-NT(8–13) administered intravenously at dose of 0.3 mg/mouse. *P < 0.01, t test.