title: 203Pb-labeled alpha-melanocyte-stimulating hormone peptide as an imaging probe for melanoma detection.
abstract: Peptide-targeted alpha-therapy with 7.4 MBq of (212)Pb-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-ReO-[Cys(3,4,10),d-Phe(7),Arg(11)]alpha-MSH(3-13) ((212)Pb-DOTA-Re(Arg(11))CCMSH) cured 45% of B16/F1 murine melanoma-bearing C57 mice in a 120-d study, highlighting its melanoma treatment potential. However, there is a need to develop an imaging surrogate for patient-specific dosimetry and to monitor the tumor response to (212)Pb-DOTA-Re(Arg(11))CCMSH therapy. The purpose of this study was to evaluate the potential of (203)Pb-DOTA-Re(Arg(11))CCMSH as a matched-pair SPECT agent for (212)Pb-DOTA-Re(Arg(11))CCMSH.
  
  
  METHODS
  DOTA-Re(Arg(11))CCMSH was labeled with (203)Pb in 0.5 M NH(4)OAc buffer at pH 5.4. The internalization and efflux of (203)Pb-DOTA-Re(Arg(11))CCMSH were determined in B16/F1 melanoma cells. The pharmacokinetics of (203)Pb-DOTA-Re(Arg(11))CCMSH was examined in B16/F1 melanoma-bearing C57 mice. A micro-SPECT/CT study was performed with (203)Pb-DOTA-Re(Arg(11))CCMSH in a B16/F1 melanoma-bearing C57 mouse at 2 h after injection.
  
  
  RESULTS
  (203)Pb-DOTA-Re(Arg(11))CCMSH was easily prepared in NH(4)OAc buffer and completely separated from the excess nonradiolabeled peptide by reversed-phase high-performance liquid chromatography (RP-HPLC). (203)Pb-DOTA-Re(Arg(11))CCMSH displayed fast internalization and extended retention in B16/F1 cells. Approximately 73% of (203)Pb-DOTA-Re(Arg(11))CCMSH activity internalized after a 20-min incubation at 25 degrees C. After incubation of the cells in culture medium for 20 min, 78% of internalized activity remained in the cells. (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited a biodistribution pattern similar to that of (212)Pb-DOTA-Re(Arg(11))CCMSH in B16/F1 melanoma-bearing mice. (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited a peak tumor uptake of 12.00+/-3.20 percentage injected dose per gram (%ID/g) at 1 h after injection. The tumor uptake gradually decreased to 3.43+/-1.12 %ID/g at 48 h after injection. (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited a peak tumor-to-kidney uptake ratio of 1.53 at 2 h after injection. The absorbed doses to the tumor and kidneys were 4.32 and 4.35 Gy, respectively, per 37 MBq. Whole-body clearance of (203)Pb-DOTA-Re(Arg(11))CCMSH was fast, with approximately 89% of the injected activity cleared through the urinary system by 2 h after injection. (203)Pb showed 1.6-mm SPECT resolution, which was comparable to (99m)Tc. Melanoma lesions were visualized through SPECT/CT images of (203)Pb-DOTA-Re(Arg(11))CCMSH at 2 h after injection.
  
  
  CONCLUSIONS
  (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited favorable pharmacokinetic and tumor imaging properties, highlighting its potential as a matched-pair SPECT agent for (212)Pb-DOTA-Re(Arg(11))CCMSH melanoma treatment.
authors.affiliation: Department of Dermatology, University of New Mexico, Albuquerque, New Mexico 87131, USA. ymiao@salud.unm.edu
authors.forename: Yubin
authors.initials: Y
authors.lastname: Miao
authors.forename: Said D
authors.initials: SD
authors.lastname: Figueroa
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Fisher
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Moore
authors.forename: Richard F
authors.initials: RF
authors.lastname: Testa
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Hoffman
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Quinn
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D007856:Lead Radioisotopes; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000378:metabolism; D051379:Mice; D015609:Organotechnetium Compounds; D010446:Peptide Fragments / Q000737:chemistry; D019047:Phantoms, Imaging; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D000521:alpha-MSH / Q000737:chemistry* / Q000378:metabolism
chemical_list: C487558:Ac-Cys-Cys-Glu-His-D-Phe-Arg-Trp-Cys-Lys-Pro-Val-NH2; D006573:Heterocyclic Compounds, 1-Ring; D007856:Lead Radioisotopes; D015609:Organotechnetium Compounds; D010446:Peptide Fragments; D044102:Receptor, Melanocortin, Type 1; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D000521:alpha-MSH