Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

MC1R and melanin-based molecular probes for theranostic of melanoma and beyond

Abstract

Malignant melanoma is accounting for most of skin cancer-associated mortality. The incidence of melanoma increased every year worldwide especially in western countries. Treatment efficiency is highly related to the stage of melanoma. Therefore, accurate staging and restaging play a pivotal role in the management of melanoma patients. Though 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET) has been widely used in imaging of tumor metastases, novel radioactive probes for specific targeted imaging of both primary and metastasized melanoma are still desired. Melanocortin receptor 1 (MC1R) and melanin are two promising biomarkers specifically for melanoma, and numerous research groups including us have been actively developing a plethora of radioactive probes based on targeting of MC1R or melanin for over two decades. In this review, some of the MC1R-targeted tracers and melanin-associated molecular imaging probes developed in our research and others have been briefly summarized, and it provides a quick glance of melanoma-targeted probe design and may contribute to further developing novel molecular probes for cancer theranostics.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1
Fig. 2: PET images of 18F-FP-RMSH-1 and 18F-FP-RMSH-2 in vivo.
Fig. 3: Molecular structures of the probes and PET images of melanoma tumor models.
Fig. 4: The performance of 18F-P3BZA in melanoma patients.

References

  1. Cancer stat facts: melanoma of the skin. 2019. https://seer.cancer.gov/statfacts/html/melan.html.

  2. Gershenwald JE, Guy GP Jr. Stemming the rising incidence of melanoma: calling prevention to action. J Natl Cancer Inst. 2016;108:djv381.

  3. Karimkhani C, Green AC, Nijsten T, Weinstock MA, Dellavalle RP, Naghavi M, et al. The global burden of melanoma: results from the Global Burden of Disease Study 2015. Br J Dermatol. 2017;177:134–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Schadendorf D, van Akkooi ACJ, Berking C, Griewank KG, Gutzmer R, Hauschild A, et al. Melanoma. Lancet. 2018;392:971–84.

    Article  PubMed  Google Scholar 

  5. Carr S, Smith C, Wernberg J. Epidemiology and risk factors of melanoma. Surg Clin North Am. 2020;100:1–12.

    Article  PubMed  Google Scholar 

  6. Linos E, Swetter SM, Cockburn MG, Colditz GA, Clarke CA. Increasing burden of melanoma in the United States. J Invest Dermatol. 2009;129:1666–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Guy GP Jr., Thomas CC, Thompson T, Watson M, Massetti GM, Richardson LC, et al. Vital signs: melanoma incidence and mortality trends and projections—United States, 1982-2030. MMWR Morb Mortal Wkly Rep. 2015;64:591–6.

    PubMed  PubMed Central  Google Scholar 

  8. Whiteman DC, Green AC, Olsen CM. The growing burden of invasive melanoma: projections of incidence rates and numbers of new cases in six susceptible populations through 2031. J Invest Dermatol. 2016;136:1161–71.

    Article  CAS  PubMed  Google Scholar 

  9. Welch HG, Mazer BL, Adamson AS. The rapid rise in cutaneous melanoma diagnoses. N Engl J Med. 2021;384:72–9.

    Article  PubMed  Google Scholar 

  10. Joyce D, Skitzki JJ. Surgical management of primary cutaneous melanoma. Surg Clin North Am. 2020;100:61–70.

    Article  PubMed  Google Scholar 

  11. Survival rates for melanoma skin cancer. 2022. https://www.cancer.org/cancer/melanoma-skin-cancer/detection-diagnosis-staging/survival-ratesfor-melanoma-skin-cancer-by-stage.html.

  12. Singh AD, Topham A. Survival rates with uveal melanoma in the United States: 1973–1997. Ophthalmology. 2003;110:962–5.

    Article  PubMed  Google Scholar 

  13. Brozyna AA, Jozwicki W, Carlson JA, Slominski AT. Melanogenesis affects overall and disease-free survival in patients with stage III and IV melanoma. Hum Pathol. 2013;44:2071–4.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Abbasi NR, Shaw HM, Rigel DS, Friedman RJ, McCarthy WH, Osman I, et al. Early diagnosis of cutaneous melanoma: revisiting the ABCD criteria. J Am Med Assoc. 2004;292:2771–6.

    Article  CAS  Google Scholar 

  15. Rigel DS, Russak J, Friedman R. The evolution of melanoma diagnosis: 25 years beyond the ABCDs. CA Cancer J Clin. 2010;60:301–16.

    Article  PubMed  Google Scholar 

  16. Tatro JB, Atkins M, Mier JW, Hardarson S, Wolfe H, Smith T, et al. Melanotropin receptors demonstrated in situ in human melanoma. J Clin Invest. 1990;85:1825–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg. 1970;172:902–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Scolyer RA, Long GV, Thompson JF. Evolving concepts in melanoma classification and their relevance to multidisciplinary melanoma patient care. Mol Oncol. 2011;5:124–36.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lee C, Collichio F, Ollila D, Moschos S. Historical review of melanoma treatment and outcomes. Clin Dermatol. 2013;31:141–7.

    Article  PubMed  Google Scholar 

  20. Rebecca VW, Sondak VK, Smalley KS. A brief history of melanoma: from mummies to mutations. Melanoma Res. 2012;22:114–22.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Belhocine TZ, Scott AM, Even-Sapir E, Urbain JL, Essner R. Role of nuclear medicine in the management of cutaneous malignant melanoma. J Nucl Med. 2006;47:957–67.

    PubMed  Google Scholar 

  22. Dancey AL, Mahon BS, Rayatt SS. A review of diagnostic imaging in melanoma. J Plast Reconstr Aesthet Surg. 2008;61:1275–83.

    Article  CAS  PubMed  Google Scholar 

  23. Davis LE, Shalin SC, Tackett AJ. Current state of melanoma diagnosis and treatment. Cancer Biol Ther. 2019;20:1366–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Perissinotti A, Rietbergen DD, Vidal-Sicart S, Riera AA, Olmos RAV. Melanoma & nuclear medicine: new insights & advances. Melanoma Manag. 2018;5:MMT06.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Schwimmer J, Essner R, Patel A, Jahan SA, Shepherd JE, Park K, et al. A review of the literature for whole-body FDG PET in the management of patients with melanoma. Q J Nucl Med. 2000;44:153–67.

    CAS  PubMed  Google Scholar 

  26. Crippa F, Leutner M, Belli F, Gallino F, Greco M, Pilotti S, et al. Which kinds of lymph node metastases can FDG PET detect? A clinical study in melanoma. J Nucl Med. 2000;41:1491–4.

    CAS  PubMed  Google Scholar 

  27. Ghanem N, Altehoefer C, Hogerle S, Nitzsche E, Lohrmann C, Schafer O, et al. Detectability of liver metastases in malignant melanoma: prospective comparison of magnetic resonance imaging and positron emission tomography. Eur J Radiol. 2005;54:264–70.

    Article  PubMed  Google Scholar 

  28. Vercellino L, de Jong D, Dercle L, Hosten B, Braumuller B, Das JP, et al. Translating molecules into imaging—the development of new PET tracers for patients with melanoma. Diagnostics. 2022;12:1116.

  29. Annunziata S, Laudicella R, Caobelli F, Pizzuto DA, Aimn Working Group Y. Clinical value of PET/CT in staging melanoma and potential new radiotracers. Curr Radiopharm. 2020;13:6–13.

    Article  CAS  PubMed  Google Scholar 

  30. Holcomb NC, Bautista RM, Jarrett SG, Carter KM, Gober MK, D’Orazio JA. cAMP-mediated regulation of melanocyte genomic instability: a melanoma-preventive strategy. Adv Protein Chem Struct Biol. 2019;115:247–95.

    Article  CAS  PubMed  Google Scholar 

  31. Wolf Horrell EM, Boulanger MC, D’Orazio JA. Melanocortin 1 receptor: structure, function, and regulation. Front Genet. 2016;7:95.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Landi MT, Bauer J, Pfeiffer RM, Elder DE, Hulley B, Minghetti P, et al. MC1R germline variants confer risk for BRAF-mutant melanoma. Science. 2006;313:521–2.

    Article  CAS  PubMed  Google Scholar 

  33. Raimondi S, Sera F, Gandini S, Iodice S, Caini S, Maisonneuve P, et al. MC1R variants, melanoma and red hair color phenotype: a meta-analysis. Int J Cancer. 2008;122:2753–60.

    Article  CAS  PubMed  Google Scholar 

  34. Fargnoli MC, Gandini S, Peris K, Maisonneuve P, Raimondi S. MC1R variants increase melanoma risk in families with CDKN2A mutations: a meta-analysis. Eur J Cancer. 2010;46:1413–20.

    Article  CAS  PubMed  Google Scholar 

  35. Kanetsky PA, Panossian S, Elder DE, Guerry D, Ming ME, Schuchter L, et al. Does MC1R genotype convey information about melanoma risk beyond risk phenotypes? Cancer. 2010;116:2416–28.

    CAS  PubMed  Google Scholar 

  36. Puntervoll HE, Yang XR, Vetti HH, Bachmann IM, Avril MF, Benfodda M, et al. Melanoma prone families with CDK4 germline mutation: phenotypic profile and associations with MC1R variants. J Med Genet. 2013;50:264–70.

    Article  CAS  PubMed  Google Scholar 

  37. Pasquali E, Garcia-Borron JC, Fargnoli MC, Gandini S, Maisonneuve P, Bagnardi V, et al. MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project. Int J Cancer. 2015;136:618–31.

    CAS  PubMed  Google Scholar 

  38. Swope VB, Jameson JA, McFarland KL, Supp DM, Miller WE, McGraw DW, et al. Defining MC1R regulation in human melanocytes by its agonist alpha-melanocortin and antagonists agouti signaling protein and beta-defensin 3. J Invest Dermatol. 2012;132:2255–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Rosenkranz AA, Slastnikova TA, Durymanov MO, Sobolev AS. Malignant melanoma and melanocortin 1 receptor. Biochemistry. 2013;78:1228–37.

    CAS  PubMed  Google Scholar 

  40. Salazar-Onfray F, Lopez M, Lundqvist A, Aguirre A, Escobar A, Serrano A, et al. Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker. Br J Cancer. 2002;87:414–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Catania A, Lipton JM. alpha-Melanocyte stimulating hormone in the modulation of host reactions. Endocr Rev. 1993;14:564–76.

    CAS  PubMed  Google Scholar 

  42. Miller R, Aaron W, Toneff T, Vishnuvardhan D, Beinfeld MC, Hook VY. Obliteration of alpha-melanocyte-stimulating hormone derived from POMC in pituitary and brains of PC2-deficient mice. J Neurochem. 2003;86:556–63.

    Article  CAS  PubMed  Google Scholar 

  43. Bagutti C, Stolz B, Albert R, Bruns C, Pless J, Eberle AN. [111In]-DTPA-labeled analogues of alpha-melanocyte-stimulating hormone for melanoma targeting: receptor binding in vitro and in vivo. Int J Cancer. 1994;58:749–55.

    Article  CAS  PubMed  Google Scholar 

  44. Cowell SM, Balse-Srinivasan PM, Ahn JM, Hruby VJ. Design and synthesis of peptide antagonists and inverse agonists for G protein-coupled receptors. Methods Enzymol. 2002;343:49–72.

    Article  PubMed  Google Scholar 

  45. Raposinho PD, Correia JD, Oliveira MC, Santos I. Melanocortin-1 receptor-targeting with radiolabeled cyclic alpha-melanocyte-stimulating hormone analogs for melanoma imaging. Biopolymers. 2010;94:820–9.

    Article  CAS  PubMed  Google Scholar 

  46. Hruby VJ, Cai M, Grieco P, Han G, Kavarana M, Trivedi D. Exploring the stereostructural requirements of peptide ligands for the melanocortin receptors. Ann N Y Acad Sci. 2003;994:12–20.

    Article  CAS  PubMed  Google Scholar 

  47. Abdel-Malek ZA, Ruwe A, Kavanagh-Starner R, Kadekaro AL, Swope V, Haskell-Luevano C, et al. alpha-MSH tripeptide analogs activate the melanocortin 1 receptor and reduce UV-induced DNA damage in human melanocytes. Pigment Cell Melanoma Res. 2009;22:635–44.

    Article  CAS  PubMed  Google Scholar 

  48. Heppeler A, Froidevaux S, Eberle AN, Maecke HR. Receptor targeting for tumor localisation and therapy with radiopeptides. Curr Med Chem. 2000;7:971–94.

    Article  CAS  PubMed  Google Scholar 

  49. Quinn T, Zhang X, Miao Y. Targeted melanoma imaging and therapy with radiolabeled alpha-melanocyte stimulating hormone peptide analogues. G Ital Dermatol Venereol. 2010;145:245–58.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Wei W, Ehlerding EB, Lan X, Luo Q, Cai W. PET and SPECT imaging of melanoma: the state of the art. Eur J Nucl Med Mol Imaging. 2018;45:132–50.

    Article  CAS  PubMed  Google Scholar 

  51. Sawyer TK, Sanfilippo PJ, Hruby VJ, Engel MH, Heward CB, Burnett JB, et al. 4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity. Proc Natl Acad Sci USA. 1980;77:5754–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Giblin MF, Wang N, Hoffman TJ, Jurisson SS, Quinn TP. Design and characterization of alpha-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination. Proc Natl Acad Sci USA. 1998;95:12814–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Froidevaux S, Calame-Christe M, Schuhmacher J, Tanner H, Saffrich R, Henze M, et al. A gallium-labeled DOTA-alpha-melanocyte-stimulating hormone analog for PET imaging of melanoma metastases. J Nucl Med. 2004;45:116–23.

    CAS  PubMed  Google Scholar 

  54. Froidevaux S, Calame-Christe M, Tanner H, Eberle AN. Melanoma targeting with DOTA-alpha-melanocyte-stimulating hormone analogs: structural parameters affecting tumor uptake and kidney uptake. J Nucl Med. 2005;46:887–95.

    CAS  PubMed  Google Scholar 

  55. Yang Y, Dickinson C, Haskell-Luevano C, Gantz I. Molecular basis for the interaction of [Nle4,D-Phe7]melanocyte stimulating hormone with the human melanocortin-1 receptor. J Biol Chem. 1997;272:23000–10.

    Article  CAS  PubMed  Google Scholar 

  56. Roxin A, Zheng G. Flexible or fixed: a comparative review of linear and cyclic cancer-targeting peptides. Future Med Chem. 2012;4:1601–18.

    Article  CAS  PubMed  Google Scholar 

  57. Conibear AC, Chaousis S, Durek T, Rosengren KJ, Craik DJ, Schroeder CI. Approaches to the stabilization of bioactive epitopes by grafting and peptide cyclization. Biopolymers. 2016;106:89–100.

    Article  CAS  PubMed  Google Scholar 

  58. Klemba M, Gardner KH, Marino S, Clarke ND, Regan L. Novel metal-binding proteins by design. Nat Struct Biol. 1995;2:368–73.

    Article  CAS  PubMed  Google Scholar 

  59. Lau SJ, Laussac JP, Sarkar B. Synthesis and copper(II)-binding properties of the N-terminal peptide of human alpha-fetoprotein. Biochem J. 1989;257:745–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Franco R, Moura JJ, Moura I, Lloyd SG, Huynh BH, Forbes WS, et al. Characterization of the iron-binding site in mammalian ferrochelatase by kinetic and Mossbauer methods. J Biol Chem. 1995;270:26352–7.

    Article  CAS  PubMed  Google Scholar 

  61. Chen J, Cheng Z, Hoffman TJ, Jurisson SS, Quinn TP. Melanoma-targeting properties of 99mtechnetium-labeled cyclic alpha-melanocyte-stimulating hormone peptide analogues. Cancer Res. 2000;60:5649–58.

    CAS  PubMed  Google Scholar 

  62. Chen J, Cheng Z, Owen NK, Hoffman TJ, Miao Y, Jurisson SS, et al. Evaluation of an 111In-DOTA-rhenium cyclized alpha-MSH analog: a novel cyclic-peptide analog with improved tumor-targeting properties. J Nucl Med. 2001;42:1847–55.

    CAS  PubMed  Google Scholar 

  63. Chen J, Cheng Z, Miao Y, Jurisson SS, Quinn TP. Alpha-melanocyte-stimulating hormone peptide analogs labeled with technetium-99m and indium-111 for malignant melanoma targeting. Cancer. 2002;94:1196–201.

    Article  CAS  PubMed  Google Scholar 

  64. Cheng Z, Chen J, Miao Y, Owen NK, Quinn TP, Jurisson SS. Modification of the structure of a metallopeptide: synthesis and biological evaluation of 111In-labeled DOTA-conjugated rhenium-cyclized alpha-MSH analogues. J Med Chem. 2002;45:3048–56.

    Article  CAS  PubMed  Google Scholar 

  65. Cheng Z, Chen J, Quinn TP, Jurisson SS. Radioiodination of rhenium cyclized alpha-melanocyte-stimulating hormone resulting in enhanced radioactivity localization and retention in melanoma. Cancer Res. 2004;64:1411–8.

    Article  CAS  PubMed  Google Scholar 

  66. Cheng Z, Xiong Z, Subbarayan M, Chen X, Gambhir SS. 64Cu-labeled alpha-melanocyte-stimulating hormone analog for microPET imaging of melanocortin 1 receptor expression. Bioconjug Chem. 2007;18:765–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. McQuade P, Miao Y, Yoo J, Quinn TP, Welch MJ, Lewis JS. Imaging of melanoma using 64Cu- and 86Y-DOTA-ReCCMSH(Arg11), a cyclized peptide analogue of alpha-MSH. J Med Chem. 2005;48:2985–92.

    Article  CAS  PubMed  Google Scholar 

  68. Rogers BE, Bigott HM, McCarthy DW, Della Manna D, Kim J, Sharp TL, et al. MicroPET imaging of a gastrin-releasing peptide receptor-positive tumor in a mouse model of human prostate cancer using a 64Cu-labeled bombesin analogue. Bioconjug Chem. 2003;14:756–63.

    Article  CAS  PubMed  Google Scholar 

  69. Cheng Z, Zhang L, Graves E, Xiong Z, Dandekar M, Chen X, et al. Small-animal PET of melanocortin 1 receptor expression using a 18F-labeled alpha-melanocyte-stimulating hormone analog. J Nucl Med. 2007;48:987–94.

    Article  CAS  PubMed  Google Scholar 

  70. Ren G, Liu Z, Miao Z, Liu H, Subbarayan M, Chin FT, et al. PET of malignant melanoma using 18F-labeled metallopeptides. J Nucl Med. 2009;50:1865–72.

    Article  CAS  PubMed  Google Scholar 

  71. Ren G, Liu S, Liu H, Miao Z, Cheng Z. Radiofluorinated rhenium cyclized alpha-MSH analogues for PET imaging of melanocortin receptor 1. Bioconjug Chem. 2010;21:2355–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Jiang H, Kasten BB, Liu H, Qi S, Liu Y, Tian M, et al. Novel, cysteine-modified chelation strategy for the incorporation of [MICO3](+) (M = Re, 99mTc) in an alpha-MSH peptide. Bioconjug Chem. 2012;23:2300–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kasten BB, Ma X, Liu H, Hayes TR, Barnes CL, Qi S, et al. Clickable, hydrophilic ligand for fac-[MICO3](+) (M = Re/99mTc) applied in an S-functionalized alpha-MSH peptide. Bioconjug Chem. 2014;25:579–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Guo H, Yang J, Gallazzi F, Miao Y. Effects of the amino acid linkers on the melanoma-targeting and pharmacokinetic properties of 111In-labeled lactam bridge-cyclized alpha-MSH peptides. J Nucl Med. 2011;52:608–16.

    Article  CAS  PubMed  Google Scholar 

  75. Guo H, Gallazzi F, Miao Y. Gallium-67-labeled lactam bridge-cyclized alpha-MSH peptides with enhanced melanoma uptake and reduced renal uptake. Bioconjug Chem. 2012;23:1341–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Guo H, Miao Y. Cu-64-labeled lactam bridge-cyclized alpha-MSH peptides for PET imaging of melanoma. Mol Pharm. 2012;9:2322–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Yang J, Xu J, Gonzalez R, Lindner T, Kratochwil C, Miao Y. (68)Ga-DOTA-GGNle-CycMSHhex targets the melanocortin-1 receptor for melanoma imaging. Sci Transl Med. 2018;10:eaau4445.

  78. Zhang C, Zhang Z, Lin KS, Lau J, Zeisler J, Colpo N, et al. Melanoma imaging using 18F-labeled alpha-melanocyte-stimulating hormone derivatives with positron emission tomography. Mol Pharm. 2018;15:2116–22.

    Article  CAS  PubMed  Google Scholar 

  79. Qiao Z, Xu J, Gonzalez R, Miao Y. Novel 64Cu-labeled NOTA-conjugated lactam-cyclized alpha-melanocyte-stimulating hormone peptides with enhanced tumor to kidney uptake ratios. Mol Pharm. 2022;19:2535–41.

  80. Miao Y, Quinn TP. Peptide-targeted radionuclide therapy for melanoma. Crit Rev Oncol Hematol. 2008;67:213–28.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Norain A, Dadachova E. Targeted radionuclide therapy of melanoma. Semin Nucl Med. 2016;46:250–9.

    Article  PubMed  Google Scholar 

  82. Miao Y, Quinn TP. Advances in receptor-targeted radiolabeled peptides for melanoma imaging and therapy. J Nucl Med. 2021;62:313–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Simon JD. Spectroscopic and dynamic studies of the epidermal chromophores trans-urocanic acid and eumelanin. Acc Chem Res. 2000;33:307–13.

    Article  CAS  PubMed  Google Scholar 

  84. Noonan FP, Zaidi MR, Wolnicka-Glubisz A, Anver MR, Bahn J, Wielgus A, et al. Melanoma induction by ultraviolet A but not ultraviolet B radiation requires melanin pigment. Nat Commun. 2012;3:884.

    Article  PubMed  Google Scholar 

  85. Larsson BS. Interaction between chemicals and melanin. Pigment Cell Res. 1993;6:127–33.

    Article  CAS  PubMed  Google Scholar 

  86. Jimbow K, Quevedo WC Jr., Fitzpatrick TB, Szabo G. Some aspects of melanin biology: 1950-1975. J Invest Dermatol. 1976;67:72–89.

    Article  CAS  PubMed  Google Scholar 

  87. Ings RMJ. The melanin binding of drugs and its implications. Drug Metab Rev. 1984;15:1183–212.

    Article  CAS  PubMed  Google Scholar 

  88. Koch SE, Lange JR. Amelanotic melanoma: the great masquerader. J Am Acad Dermatol. 2000;42:731–4.

    Article  CAS  PubMed  Google Scholar 

  89. Wee E, Wolfe R, McLean C, Kelly JW, Pan Y. Clinically amelanotic or hypomelanotic melanoma: anatomic distribution, risk factors, and survival. J Am Acad Dermatol. 2018;79:645–51.

    Article  PubMed  Google Scholar 

  90. Slominski RM, Zmijewski MA, Slominski AT. The role of melanin pigment in melanoma. Exp Dermatol. 2015;24:258–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Brozyna AA, Jozwicki W, Roszkowski K, Filipiak J, Slominski AT. Melanin content in melanoma metastases affects the outcome of radiotherapy. Oncotarget. 2016;7:17844–53.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Rouanet J, Quintana M, Auzeloux P, Cachin F, Degoul F. Benzamide derivative radiotracers targeting melanin for melanoma imaging and therapy: preclinical/clinical development and combination with other treatments. Pharmacol Ther. 2021;224:107829.

    Article  CAS  PubMed  Google Scholar 

  93. Link E, Lukiewicz S. A new radioactive drug selectively accumulating in melanoma-cells. Eur J Nucl Med. 1982;7:469–73.

    Article  CAS  PubMed  Google Scholar 

  94. Michelot JM, Moreau MC, Labarre PG, Madelmont JC, Veyre AJ, Papon JM, et al. Synthesis and evaluation of new iodine-125 radiopharmaceuticals as potential tracers for malignant melanoma. Nucl Med. 1991;32:1573–80.

    CAS  Google Scholar 

  95. Michelot JM, Moreau MF, Veyre AJ, Bonafous JF, Bacin FJ, Madelmont JC, et al. Phase II scintigraphic clinical trial of malignant melanoma and metastases with iodine-123-N-(2-diethylaminoethyl 4-iodobenzamide). J Nucl Med. 1993;34:1260–6.

    CAS  PubMed  Google Scholar 

  96. Moins N, D’Incan M, Bonafous J, Bacin F, Labarre P, Moreau MF, et al. 123I-N-(2-diethylaminoethyl)-2-iodobenzamide: a potential imaging agent for cutaneous melanoma staging. Eur J Nucl Med Mol Imaging. 2002;29:1478–84.

    Article  CAS  PubMed  Google Scholar 

  97. Cachin F, Miot-Noirault E, Gillet B, Isnardi V, Labeille B, Payoux P, et al. 123I-BZA2 as a melanin-targeted radiotracer for the identification of melanoma metastases: results and perspectives of a multicenter phase III clinical trial. J Nucl Med. 2014;55:15–22.

  98. Ren G, Miao Z, Liu H, Jiang L, Limpa-Amara N, Mahmood A, et al. Melanin-targeted preclinical PET imaging of melanoma metastasis. J Nucl Med. 2009;50:1692–9.

    Article  CAS  PubMed  Google Scholar 

  99. Greguric I, Taylor SR, Denoyer D, Ballantyne P, Berghofer P, Roselt P, et al. Discovery of [18F]N-(2-(Diethylamino)ethyl)-6-fluoronicotinamide: a melanoma positron emission tomography imaging radiotracer with high tumor to body contrast ratio and rapid renal clearance. J Med Chem. 2009;52:5299–302.

    Article  CAS  PubMed  Google Scholar 

  100. Denoyer D, Greguric I, Roselt P, Neels OC, Aide N, Taylor SR, et al. High-contrast PET of melanoma using 18F-MEL050, a selective probe for melanin with predominantly renal clearance. J Nucl Med. 2010;51:441–7.

    Article  CAS  PubMed  Google Scholar 

  101. Liu H, Liu S, Miao Z, Deng Z, Shen B, Hong X, et al. Development of 18F-labeled picolinamide probes for PET imaging of malignant melanoma. J Med Chem. 2013;56:895–901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Qin C, Cheng K, Chen K, Hu X, Liu Y, Lan X, et al. Tyrosinase as a multifunctional reporter gene for photoacoustic/MRI/PET triple modality molecular imaging. Sci Rep. 2013;3:1490.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Bu L, Li R, Liu H, Feng W, Xiong X, Zhao H, et al. Intrastriatal transplantation of retinal pigment epithelial cells for the treatment of Parkinson disease: in vivo longitudinal molecular imaging with 18F-P3BZA PET/CT. Radiology. 2014;272:174–83.

    Article  PubMed  Google Scholar 

  104. Liu H, Liu S, Miao Z, Jiang H, Deng Z, Hong X, et al. A novel aliphatic 18F-labeled probe for PET imaging of melanoma. Mol Pharmacol. 2013;10:3384–91.

    Article  CAS  Google Scholar 

  105. Ma X, Wang S, Wang S, Liu D, Zhao X, Chen H, et al. Biodistribution, radiation dosimetry, and clinical application of a melanin-targeted PET probe, 18F-P3BZA, in patients. J Nucl Med. 2019;60:16–22.

    Article  CAS  PubMed  Google Scholar 

  106. Hong Z, Yu B, Xiao J, Feng H, Ma X, Cheng Z, et al. A convenient and efficient solid phase extraction-based pathway for purification of melanin-targeted probe 18F-P3BZA. Microchem J. 2021;164:106008.

  107. Pyo A, Kim DY, Kim H, Lim D, Kwon SY, Kang SR, et al. Ultrasensitive detection of malignant melanoma using PET molecular imaging probes. Proc Natl Acad Sci USA. 2020;117:12991–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Zhang X, Li M, Gai Y, Chen J, Tao J, Yang L, et al. 18F-PFPN PET: a new and attractive imaging modality for patients with malignant melanoma. J Nucl Med. 2022;jnumed.121.263179.

  109. Zhang X, Li M, Lan X. Melanin-targeted PET imaging with 18F-PFPN for identifying gastric metastatic melanoma. Clin Nucl Med. 2022;47:666–7.

    Article  CAS  PubMed  Google Scholar 

  110. Fan Q, Cheng K, Hu X, Ma X, Zhang R, Yang M, et al. Transferring biomarker into molecular probe: melanin nanoparticle as a naturally active platform for multimodality imaging. J Am Chem Soc. 2014;136:15185–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Yang M, Fan Q, Zhang R, Cheng K, Yan J, Pan D, et al. Dragon fruit-like biocage as an iron trapping nanoplatform for high efficiency targeted cancer multimodality imaging. Biomaterials. 2015;69:30–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Zhang R, Fan Q, Yang M, Cheng K, Lu X, Zhang L, et al. Engineering melanin nanoparticles as an efficient drug-delivery system for imaging-guided chemotherapy. Adv Mater. 2015;27:5063–9.

    Article  CAS  PubMed  Google Scholar 

  113. Hong SH, Sun Y, Tang C, Cheng K, Zhang R, Fan Q, et al. Chelator-free and biocompatible melanin nanoplatform with facile-loading gadolinium and copper-64 for bioimaging. Bioconjug Chem. 2017;28:1925–30.

    Article  CAS  PubMed  Google Scholar 

  114. Xia L, Guo X, Liu T, Xu X, Jiang J, Wang F, et al. Multimodality imaging of naturally active melanin nanoparticles targeting somatostatin receptor subtype 2 in human small-cell lung cancer. Nanoscale. 2019;11:14400–9.

    Article  CAS  PubMed  Google Scholar 

  115. Shi H, Suo Y, Zhang Z, Liu R, Liu H, Cheng Z. Copper(II)-disulfiram loaded melanin-dots for cancer theranostics. Nanomedicine. 2021;32:102340.

    Article  CAS  PubMed  Google Scholar 

  116. Sun T, Jiang D, Rosenkrans ZT, Ehlerding EB, Ni D, Qi C, et al. A melanin-based natural antioxidant defense nanosystem for theranostic application in acute kidney injury. Adv Funct Mater. 2019;29:1904833.

  117. Xia L, Meng X, Wen L, Zhou N, Liu T, Xu X, et al. A highly specific multiple enhancement theranostic nanoprobe for PET/MRI/PAI image-guided radioisotope combined photothermal therapy in prostate cancer. Small. 2021;17:e2100378.

    Article  PubMed  Google Scholar 

  118. Zhao X, Sun J, Dong J, Guo C, Cai W, Han J, et al. An auto-photoacoustic melanin-based drug delivery nano-platform for self-monitoring of acute kidney injury therapy via a triple-collaborative strategy. Acta Biomater. 2022;147:327–41.

    Article  CAS  PubMed  Google Scholar 

  119. Ball V. Polydopamine films and particles with catalytic activity. Catal Today. 2018;301:196–203.

    Article  CAS  Google Scholar 

  120. Ball V. Polydopamine nanomaterials: recent advances in synthesis methods and applications. Front Bioeng Biotechnol. 2018;6:109.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Ryu JH, Messersmith PB, Lee H. Polydopamine surface chemistry: a decade of discovery. ACS Appl Mater Interfaces. 2018;10:7523–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Ambekar RS, Kandasubramanian B. A polydopamine-based platform for anti-cancer drug delivery. Biomater Sci. 2019;7:1776–93.

    Article  CAS  PubMed  Google Scholar 

  123. Cheng W, Zeng X, Chen H, Li Z, Zeng W, Mei L, et al. Versatile polydopamine platforms: synthesis and promising applications for surface modification and advanced nanomedicine. ACS Nano. 2019;13:8537–65.

    Article  CAS  PubMed  Google Scholar 

  124. Huang Q, Chen J, Liu M, Huang H, Zhang X, Wei Y. Polydopamine-based functional materials and their applications in energy, environmental, and catalytic fields: state-of-the-art review. Chem Eng J. 2020;387:124019.

  125. Lee HA, Park E, Lee H. Polydopamine and its derivative surface chemistry in material science: a focused review for studies at KAIST. Adv Mater. 2020;32:e1907505.

    Article  PubMed  Google Scholar 

  126. Palangka C, Hanaoka H, Yamaguchi A, Murakami T, Tsushima Y. Al18F-labeled alpha-melanocyte-stimulating hormone (alpha-MSH) peptide derivative for the early detection of melanoma. Ann Nucl Med. 2019;33:733–9.

    Article  CAS  PubMed  Google Scholar 

  127. Xu J, Yang J, Gonzalez R, Fisher DR, Miao Y. Melanoma-targeting property of Y-90-labeled lactam-cyclized alpha-melanocyte-stimulating hormone peptide. Cancer Biother Radiopharm. 2019;34:597–603.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Yang J, Xu J, Cheuy L, Gonzalez R, Fisher DR, Miao Y. Evaluation of a novel Pb-203-labeled lactam-cyclized alpha-melanocyte-stimulating hormone peptide for melanoma targeting. Mol Pharm. 2019;16:1694–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Qiao Z, Xu J, Gonzalez R, Miao Y. Novel [99mTc]-tricarbonyl-NOTA-conjugated lactam-cyclized alpha-MSH peptide with enhanced melanoma uptake and reduced renal uptake. Mol Pharm. 2020;17:3581–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Xu J, Qiao Z, Gonzalez R, Miao Y. Facile preparation of a novel Ga-67-labeled NODAGA-conjugated lactam-cyclized alpha-MSH peptide at room temperature for melanoma targeting. Bioorg Med Chem Lett. 2020;30:127627.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Garg S, Kothari K, Thopate SR, Doke AK, Garg PK. Design, synthesis, and preliminary in vitro and in vivo evaluation of N-(2-diethylaminoethyl)-4-[18F]fluorobenzamide ([18F]-DAFBA): a novel potential PET probe to image melanoma tumors. Bioconjug Chem. 2009;20:583–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank funding from the Shanghai Municipal Science and Technology Major Project.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zhen Cheng.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Shi, H., Cheng, Z. MC1R and melanin-based molecular probes for theranostic of melanoma and beyond. Acta Pharmacol Sin 43, 3034–3044 (2022). https://doi.org/10.1038/s41401-022-00970-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41401-022-00970-y

Keywords

  • melanoma
  • molecular probes
  • radiotracers
  • MC1R
  • melanin

This article is cited by

Search

Quick links