Improved Detection of Regional Melanoma Metastasis Using 18F-6-Fluoro-N-[2-(Diethylamino)Ethyl] Pyridine-3-Carboxamide, a Melanin-Specific PET Probe, by Perilesional Administration (original) (raw)
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Journal of Nuclear Medicine, 2010
The aim of this study was to evaluate the novel probe 18 F-6fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide (18 F-MEL050) for the imaging of primary and metastatic melanoma. Methods: PET using 18 F-MEL050 was performed in murine models of melanoma. The specificity of 18 F-MEL050 was studied by comparing its accumulation in pigmented B16-F0 allograft tumors with that of human amelanotic A375 xenografts using PET and high-resolution autoradiography. 18 F-MEL050 PET results were compared with 18 F-FDG PET, the current standard in melanoma molecular imaging. To test the ability of 18 F-MEL050 to assess the metastatic spread of melanoma, a murine model of lung metastasis was imaged by PET/CT, and results correlated with physical assessment of tumor burden in the lungs. Results: In pigmented B16-F0 grafts, 18 F-MEL050 PET yielded a tumor-to-background ratio of approximately 20:1 at 1 h and greater than 50:1 at 2 and 3 h. In the B16-F0 melanoma allograft model, tumor-to-background ratio was more than 9-fold higher for 18 F-MEL050 than for 18 F-FDG (50.9 6 6.9 vs. 5.8 6 0.5). No uptake was observed in the amelanotic melanoma xenografts. Intense uptake of 18 F-MEL050 was evident in metastatic lesions in the lungs of B16-BL6 tumor-bearing mice on PET at 2 h after tracer injection, with high concordance between 18 F-MEL050 accumulation on PET/CT and tumor burden determined at necroscopy. Conclusion: 18 F-MEL050 has a rapid tumor uptake and high retention with specificity for melanin, suggesting great potential for noninvasive clinical evaluation of suspected metastatic melanoma.
Melanin-Targeted Preclinical PET Imaging of Melanoma Metastasis
Journal of Nuclear Medicine, 2009
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 s-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 6 1.83 percentage injected dose (%ID) per gram was observed in B16F10 tumors and only 0.75 6 0.09 %ID/g and 0.56 6 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.
Journal of Surgical Oncology, 1997
time of diagnosis is essential to providing care that simul taneously improves overall mortality while minimizing morbidity. Unfortunately, the accurate staging of disease extent in malignant melanoma remains problematic. For instance, in patients with clinical Stage I (localized) mela noma, 20%-40% will have clinically undetectable lymph node metastases, which, if left untreated will substantially worsen 5-yr mortality (3). Although computed tomography (CT)is asensitive testfor morphologically enlarged lymph nodes and larger metastases, its limited specificity and inherent insensitivity for tumors in normal sized lymph nodes and for small tumor foci in the abdomen limits its usefulness. Radiolabeled monoclonal antibody scanning has potential in this area, but has not yet been fully eval uated (4-8). A single nornnvasive test that could simulta neously assess the presence or absence of tumors in re gional lymph nodes, reliably evaluate the presence or absence of visceral metastasis and provide more optimal follow-up ofmetastatic tumors could substantially improve the detection, staging, swvefflance and thus the manage ment of malignantmelanoma.
The utility of PET-CT in the staging and management of advanced and recurrent malignant melanoma
South African Journal of Surgery, 2019
Background: Accurate pre-operative staging and correct surgical selection of patients with malignant melanoma reduces unnecessary morbidity and mortality, improves distant control and may improve survival. 18 F-fluorodeoxyglucose Positron Emission Tomography Computed Tomography (18 F-FDG PET-CT) has been shown to be useful in exclusion of metastatic sites and aids in surgical planning in stage III and potentially resectable stage IV disease. The primary objective of the study was to determine whether the use of PET-CT alters the initial staging and management of patients with advanced and recurrent melanoma. Methods: Retrospective analysis of clinical records of patients with malignant melanoma referred for staging PET-CT over a three-year period at our institution was performed. Pre-and post-PET-CT stage was recorded and a descriptive analysis was done to determine whether PET-CT resulted in a change in stage grouping and whether this change effected a change in clinical management. Results: A change in stage grouping occurred in 21/39 (53.8%) of patients, 76.2% of which were up-staged and 23.8% down staged. On analysis of stage III/IV and recurrent melanoma, a change in stage occurred in 90% of stage III, 50% of stage IV and 50% of recurrent melanoma patients. This effected a change in management in 86.7% of patients with stage III, IV and recurrent melanoma collectively. Conclusion: PET-CT is a useful tool in the staging and subsequent management of melanoma. Its utility is pronounced in advanced and recurrent melanoma.
Effectiveness of Positron Emission Tomography for the Detection of Melanoma Metastases
Annals of Surgery, 1998
The purpose of this study was to determine the sensitMty, specificity, and clinical utility of 18F 2-fluoro-2-deoxy-D-glucose (FDG) totalbody positron emission tomography (PET) scanning for the detection of metastases in patients with malignant melanoma. Summary Background Data Recent preliminary reports suggest that PET using FDG may be more sensitive and specific for detection of metastatic melanoma than standard radiologic imaging studies using computed tomography (CT). PET technology is showing utility in the detection of metastatic tumors from multiple primary sites including breast, lung, lymphoma, and melanoma. However, little information is available
Journal of Clinical Oncology, 2009
Patients with melanoma with potentially resectable lymph node metastases require accurate staging to prevent unnecessary surgery. [ 18 F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) is attractive for this because melanoma typically is FDG avid. The aim of this prospective multicenter study was to perform a head-to-head comparison of FDG-PET and computed tomography (CT) in staging of patients with melanoma with palpable lymph node metastases in terms of diagnostic accuracy and impact on treatment. Patients and Methods All consecutive patients with palpable, proven lymph node metastases of melanoma between mid 2003 and 2007 were prospectively included. The number/site of distant metastases detected with FDG-PET and CT were recorded. Histology/cytology or 6 months follow-up were the reference standard. Intended and performed treatment was recorded. Results Distant metastases were suspected by FDG-PET in 32% of the 251 patients and by CT in 29% (P ϭ .26). Upstaging was correct in 27% by FDG-PET and in 24% by CT (P ϭ .18). FDG-PET detected more metastatic sites (133 v 112, P ϭ .03), detecting significantly more bone and subcutaneous metastases. Treatment changed in 19% of patients; in 79% as a result of both scans, in 17% exclusively by FDG-PET, and in 4% exclusively by CT. In 34 patients (14%), FDG-PET had an additional value over spiral CT, and in 23 patients (9%), CT had additional value over FDG-PET. Conclusion As a result of FDG-PET and CT, 27% of patients were upstaged, and treatment changed in one of five patients. FDG-PET and CT are equivalent in upstaging; however, FDG-PET detected more metastatic sites, especially bone and subcutaneous. FDG-PET and/or CT are indicated in the staging of patients with melanoma with palpable lymph node metastases.