Synthesis and evaluation of a radioiodinated bladder cancer specific peptide.
Bladder cancer is the second most common cancer of the urinary tract, however the invasive cystoscopy is still the standard technique for diagnosis and surveillance of bladder cancer. Herein, we radiolabel bladder cancer specific peptide with radioactive iodine ((131/124)I) and evaluate its potential as a new radiopharmaceutical for the non-invasive diagnosis of bladder cancer. A 9-mer bladder cancer specific peptide (BP) was conjugated with tyrosine and cyclized by disulfide bond formation to give Y-BP, which was further radioiodinated to give [(131/124)I]Y-BP in good radiochemical yield. The biodistribution data showed the high selectivity of [(124)I]Y-BP in HT1376 human bladder cancer xenograft models with a tumor-to-muscle ratio of 6.2. This tumor targeting was not observed in control B16F10 melanoma tumor models. In microPET studies, while the control scrambled peptide, [(124)I]Y-sBP, did not accumulate in either the bladder cancer or melanoma, [(124)I]Y-BP showed high tumor uptake only in animals with HT1376 bladder cancer cells. Furthermore, [(124)I]Y-BP showed superior bladder cancer uptake even compared to most commonly used cancer imaging tracer, [(18)F]FDG. The experimental results suggest the potential of [(124)I]Y-BP as a new radiopharmaceutical for the non-invasive diagnosis of bladder cancer with high binding affinity and selectivity.
Department of Molecular Medicine, Kyungpook National University, School of Medicine, Daegu 700-422, South Korea.
Yeong Su
YS
Ha
Hwa Young
HY
Lee
Gwang Il
GI
An
Jonghee
J
Kim
Wonjung
W
Kwak
Eun-Ju
EJ
Lee
Seung-Min
SM
Lee
Byung-Heon
BH
Lee
In-San
IS
Kim
Takele
T
Belay
Woonghee
W
Lee
Byeong-Cheol
BC
Ahn
Jaetae
J
Lee
Jeongsoo
J
Yoo
D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D003500:Cyclization; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging; D051379:Mice; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D055550:Protein Stability; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D001749:Urinary Bladder Neoplasms / Q000000981:diagnostic imaging*
D007457:Iodine Radioisotopes; D010455:Peptides; D019275:Radiopharmaceuticals