PT  - JOURNAL ARTICLE
AU  - Gang Ren
AU  - Zheng Miao
AU  - Hongguang Liu
AU  - Lei Jiang
AU  - Naengnoi Limpa-Amara
AU  - Ashfaq Mahmood
AU  - Sanjiv S. Gambhir
AU  - Zhen Cheng
TI  - Melanin-Targeted Preclinical PET Imaging of Melanoma Metastasis
AID  - 10.2967/jnumed.109.066175
DP  - 2009 Oct 01
TA  - Journal of Nuclear Medicine
PG  - 1692--1699
VI  - 50
IP  - 10
4099  - http://jnm.snmjournals.org/content/50/10/1692.short
4100  - http://jnm.snmjournals.org/content/50/10/1692.full
SO  - J Nucl Med2009 Oct 01; 50
AB  - Dialkylamino-alkyl-benzamides possess an affinity for melanin, suggesting that labeling of such benzamides with 18F 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]-4-18F-fluorobenzamide (18F-FBZA) was synthesized via a 1-step conjugation reaction. The σ-receptor binding affinity of 19F-FBZA was determined along with the in vitro cellular uptake of radiofluorinated 18F-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 18F-FDG PET in the melanoma models. Results: In vitro, uptake of 18F-FBZA was significantly higher in B16F10 cells treated with l-tyrosine (P < 0.001). In vivo, 18F-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: 18F-FBZA specifically targets primary and metastatic melanotic melanoma lesions with high tumor uptake and may have translational potential.