Melanin-targeted preclinical PET imaging of melanoma metastasis.
Dialkylamino-alkyl-benzamides possess an affinity for melanin, suggesting that labeling of such benzamides with (18)F could potentially produce melanin-targeted PET probes able to identify melanotic melanoma metastases in vivo with high sensitivity and specificity.


METHODS
In this study, N-[2-(diethylamino)ethyl]-4-(18)F-fluorobenzamide ((18)F-FBZA) was synthesized via a 1-step conjugation reaction. The sigma-receptor binding affinity of (19)F-FBZA was determined along with the in vitro cellular uptake of radiofluorinated (18)F-FBZA in B16F10 cells. In vivo distribution and small-animal PET studies were conducted on mice bearing B16F10 melanoma, A375M amelanotic melanoma, and U87MG tumors, and comparative studies were performed with (18)F-FDG PET in the melanoma models.


RESULTS
In vitro, uptake of (18)F-FBZA was significantly higher in B16F10 cells treated with l-tyrosine (P < 0.001). In vivo, (18)F-FBZA displayed significant tumor uptake; at 2 h, 5.94 +/- 1.83 percentage injected dose (%ID) per gram was observed in B16F10 tumors and only 0.75 +/- 0.09 %ID/g and 0.56 +/- 0.13 %ID/g was observed in amelanotic A375M and U87MG tumors, respectively. Lung uptake was significantly higher in murine lungs bearing melanotic B16F10 pulmonary metastases than in normal murine lungs (P < 0.01). Small-animal PET clearly identified melanotic lesions in both primary and pulmonary metastasis B16F10 tumor models. Coregistered micro-CT with small-animal PET along with biopsies further confirmed the presence of tumor lesions in the mouse lungs.


CONCLUSIONS
(18)F-FBZA specifically targets primary and metastatic melanotic melanoma lesions with high tumor uptake and may have translational potential.
Ren
Gang
G
Department of Radiology and Bio-X Program, Stanford University, Stanford, California 94305, USA.
Miao
Zheng
Z
Liu
Hongguang
H
Jiang
Lei
L
Limpa-Amara
Naengnoi
N
Mahmood
Ashfaq
A
Gambhir
Sanjiv S
SS
Cheng
Zhen
Z
D000818:Animals; D001549:Benzamides / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D008543:Melanins / Q000378:metabolism*; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis / Q000000981:diagnostic imaging / Q000473:pathology; D049268:Positron-Emission Tomography; D011854:Radiochemistry; D017480:Receptors, sigma / Q000378:metabolism; D014018:Tissue Distribution
D001549:Benzamides; D005462:Fluorine Radioisotopes; D008543:Melanins; D017480:Receptors, sigma