Metastatic melanoma imaging with an (111)In-labeled lactam bridge-cyclized alpha-melanocyte-stimulating hormone peptide

Nucl Med Biol. 2009 Apr;36(3):267-76. doi: 10.1016/j.nucmedbio.2009.01.003.


Introduction: The purpose of this study was to examine whether a novel lactam bridge-cyclized (111)In-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Gly-Glu-c[Lys-Nle-Glu-His-d-Phe-Arg-Trp-Gly-Arg-Pro-Val-Asp] {DOTA-GlyGlu-CycMSH} could be an effective imaging probe for metastatic melanoma detection.

Methods: (111)In-DOTA-GlyGlu-CycMSH was prepared and purified by reverse-phase high-performance liquid chromatography (RP-HPLC). The internalization and efflux of (111)In-DOTA-GlyGlu-CycMSH were examined in B16/F10 melanoma cells. The biodistribution of (111)In-DOTA-GlyGlu-CycMSH was determined in B16/F10 pulmonary metastatic melanoma-bearing and normal C57 mice. Pulmonary metastatic melanoma imaging was performed by small-animal single-photon emission computed tomography (SPECT)/CT (Nano-SPECT/CT) using (111)In-DOTA-GlyGlu-CycMSH as an imaging probe and compared with 2-[(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG) positron emission tomography (PET) imaging.

Results: (111)In-DOTA-GlyGlu-CycMSH was readily prepared with greater than 95% radiolabeling yield. (111)In-DOTA-GlyGlu-CycMSH displayed rapid internalization and extended efflux in B16/F10 cells. (111)In-DOTA-GlyGlu-CycMSH exhibited significantly (P<.05) higher uptakes (2.00+/-0.74%ID/g at 2 h post-injection and 1.83+/-0.12%ID/g at 4 h post-injection) in metastatic melanoma-bearing lung than that in normal lung (0.08+/-0.08%ID/g and 0.05+/-0.05%ID/g at 2 and 4 h post-injection, respectively). The activity accumulation in normal organs was low (<0.5%ID/g) except for the kidneys 2 and 4 h post-injection. B16/F10 pulmonary melanoma metastases were clearly visualized with (111)In-DOTA-GlyGlu-CycMSH 2 h post-injection rather than with [(18)F]FDG 1 h post-injection.

Conclusions: (111)In-DOTA-GlyGlu-CycMSH exhibited favorable metastatic melanoma-targeting and -imaging properties, highlighting its potential as an effective imaging probe for metastatic melanoma detection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding, Competitive
  • Cell Line, Tumor
  • Feasibility Studies
  • Fluorodeoxyglucose F18 / administration & dosage
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Indium Radioisotopes
  • Lactams / chemistry*
  • Melanoma / diagnosis*
  • Melanoma / diagnostic imaging
  • Melanoma / pathology*
  • Mice
  • Neoplasm Metastasis / diagnosis*
  • Neoplasm Metastasis / diagnostic imaging
  • Neoplasm Staging
  • Peptides, Cyclic* / chemistry
  • Peptides, Cyclic* / metabolism
  • Peptides, Cyclic* / pharmacokinetics
  • Reproducibility of Results
  • Staining and Labeling
  • Time Factors
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon
  • Tomography, X-Ray Computed
  • alpha-MSH* / chemistry
  • alpha-MSH* / metabolism
  • alpha-MSH* / pharmacokinetics


  • Heterocyclic Compounds, 1-Ring
  • Indium Radioisotopes
  • Lactams
  • Peptides, Cyclic
  • Fluorodeoxyglucose F18
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • alpha-MSH