99mTc-HYNIC-D4 Peptide: A New Small Radiolabeled Peptide for Non Small Cell Lung Tumor Targeting.
OBJECTIVE
The aim of this study was to evaluate the 99mTc-HYNIC-D4 peptide as a new radiotracer for tumor targeting in non small cell lung tumor that overexpresses epidermal growth factor receptor (EGFR).


METHODS
D4 small peptide (Leu-Ala-Arg-Leu-Leu-Thr) was selected as a candidate for specific targeting on EGFR. It was conjugated with HYNIC on N-terminus and labeled with 99mTc using tricine as a co-ligand. The cellular and animal studies were evaluated for specific binding of this labeled peptide.


RESULTS
Radiochemical purity was determined to be 98% by instant thin layer chromatography and reverse-phase high performance liquid chromatography. Stability of radiolabeled peptide was more than 90% up to 24 h incubation in solution at 37 oC. Specific binding of the radiolabeled peptide to the EGFR showed dissociation constant of 181 ± 41 nM. Animal biodistribution in normal and A-549 xenografted nude mice showed rapid clearance from blood and other non target organs. Tumor uptake values as %ID/g (percentage of injection dose per gram of tissue) were 8.07% at 1 h and 3.82% at 4 h after injection that was blocked by presaturation of EGFR using an excess of cold peptide.


CONCLUSIONS
This study showed that 99mTc-HYNIC-D4 is a promising tumor targeting radiotracer on the non small cell lung tumor.
Department of Radiopharmacy, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Mona Haddad
MH
Zahmatkesh
Department of Radiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Seyed Mohammad
SM
Abedi
Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Seyed Jalal
SJ
Hosseinimehr
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000175:diagnosis; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D009842:Oligopeptides; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C540794:leucyl-alanyl-arginyl-leucyl-leucyl-threonine
99mTc; Tumor imaging; lung cancer; non small cell; peptide; small radiolabeled