UNLABELLED: 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. CONCLUSION: (18)F-FBZA specifically targets primary and metastatic melanotic melanoma lesions with high tumor uptake and may have translational potential.
UNLABELLED: 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. CONCLUSION: (18)F-FBZA specifically targets primary and metastatic melanotic melanoma lesions with high tumor uptake and may have translational potential.
Authors: Michael Eisenhut; Ashour Mohammed; Walter Mier; Frank Schönsiegel; Matthias Friebe; Ashfaq Mahmood; Alun G Jones; Uwe Haberkorn Journal: J Med Chem Date: 2002-12-19 Impact factor: 7.446
Authors: M Eisenhut; W E Hull; A Mohammed; W Mier; D Lay; W Just; K Gorgas; W D Lehmann; U Haberkorn Journal: J Med Chem Date: 2000-10-19 Impact factor: 7.446
Authors: M Friebe; A Mahmood; C Bolzati; A Drews; B Johannsen; M Eisenhut; D Kraemer; A Davison; A G Jones Journal: J Med Chem Date: 2001-09-13 Impact factor: 7.446
Authors: Xiuli Zhang; Feng Chen; Melik Z Turker; Kai Ma; Pat Zanzonico; Fabio Gallazzi; Manankumar A Shah; Austin R Prater; Ulrich Wiesner; Michelle S Bradbury; Michael R McDevitt; Thomas P Quinn Journal: Biomaterials Date: 2020-02-19 Impact factor: 12.479