Factors affecting the unexpected failure of DCE-MRI to determine the optimal biological dose of the vascular targeting agent NGR-hTNF in solid cancer patients.
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Factors affecting the unexpected failure of DCE-MRI to determine the optimal biological dose of the vascular targeting agent NGR-hTNF in solid cancer patients. / Desar, [Unbekannt]; Ingrid, M E; Herpen, van; Carla, M L; Asten, van; Jack, J A; Fiedler, Walter; Walter, [Unbekannt]; Marreaud, [Unbekannt]; Sandrine, [Unbekannt]; Timmer-Bonte, [Unbekannt]; Johanna, N H; Ter, Voert; Edwin, G W; Lambiase, [Unbekannt]; Antonio, [Unbekannt]; Bordignon, [Unbekannt]; Claudio, [Unbekannt]; Heerschap, [Unbekannt]; Arend, [Unbekannt]; Laarhoven, van; Hanneke, W M.
in: EUR J RADIOL, Jahrgang 80, Nr. 3, 3, 2011, S. 655-661.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Factors affecting the unexpected failure of DCE-MRI to determine the optimal biological dose of the vascular targeting agent NGR-hTNF in solid cancer patients.
AU - Desar, [Unbekannt]
AU - Ingrid, M E
AU - Herpen, van
AU - Carla, M L
AU - Asten, van
AU - Jack, J A
AU - Fiedler, Walter
AU - Walter, [Unbekannt]
AU - Marreaud, [Unbekannt]
AU - Sandrine, [Unbekannt]
AU - Timmer-Bonte, [Unbekannt]
AU - Johanna, N H
AU - Ter, Voert
AU - Edwin, G W
AU - Lambiase, [Unbekannt]
AU - Antonio, [Unbekannt]
AU - Bordignon, [Unbekannt]
AU - Claudio, [Unbekannt]
AU - Heerschap, [Unbekannt]
AU - Arend, [Unbekannt]
AU - Laarhoven, van
AU - Hanneke, W M
PY - 2011
Y1 - 2011
N2 - INTRODUCTION: To understand which factors could affect the assessment of anti-vascular treatment by DCE-MRI, we investigated possible causes that could have hampered the selection of an optimal biological dose in humans of the vascular targeted agent NGR-hTNF by DCE-MRI: (1) insufficient reproducibility of DCE-MRI; (2) less specific targeting of NGR-hTNF; (3) interference of vessel characteristics with NGR-hTNF efficacy; (4) interfering pharmacodynamic effects. EXPERIMENTAL: In a phase I study NGR-hTNF, DCE-MRI was performed at baseline and 2h after NGR-hTNF administration in 31 patients with advanced solid cancer. Reproducibility measurements were performed in 5 other non-treated patients with metastatic disease. Mean k(ep), K(trans) values and their histogram distribution were determined in metastases and healthy liver tissue. The correlation between tumour size and DCE-MRI parameters was determined. Kinetics of soluble TNF receptors and the development of anti-TNF antibodies were assessed. RESULTS: Reproducibility of the DCE-MRI technique was adequate. Mean DCE-MRI parameters did not significantly change after NGR-hTNF administration, but histogram analyses showed significant changes in metastases and healthy liver tissue in some patients. The anti-vascular effects of NGR-hTNF were larger in smaller tumours, which have less mature neovasculature. Soluble TNF receptors were released. CONCLUSIONS: The difficulty to find an optimal biological dose of NGR-TNF by DCE-MRI is likely caused by a combination of factors: (i) different profiles of early anti-vascular effects in tumours and healthy liver tissue, (ii) dependence of the magnitude of the anti-vascular effect of NGR-hTNF on tumour size and (iii) shedding kinetics of soluble TNF receptors.
AB - INTRODUCTION: To understand which factors could affect the assessment of anti-vascular treatment by DCE-MRI, we investigated possible causes that could have hampered the selection of an optimal biological dose in humans of the vascular targeted agent NGR-hTNF by DCE-MRI: (1) insufficient reproducibility of DCE-MRI; (2) less specific targeting of NGR-hTNF; (3) interference of vessel characteristics with NGR-hTNF efficacy; (4) interfering pharmacodynamic effects. EXPERIMENTAL: In a phase I study NGR-hTNF, DCE-MRI was performed at baseline and 2h after NGR-hTNF administration in 31 patients with advanced solid cancer. Reproducibility measurements were performed in 5 other non-treated patients with metastatic disease. Mean k(ep), K(trans) values and their histogram distribution were determined in metastases and healthy liver tissue. The correlation between tumour size and DCE-MRI parameters was determined. Kinetics of soluble TNF receptors and the development of anti-TNF antibodies were assessed. RESULTS: Reproducibility of the DCE-MRI technique was adequate. Mean DCE-MRI parameters did not significantly change after NGR-hTNF administration, but histogram analyses showed significant changes in metastases and healthy liver tissue in some patients. The anti-vascular effects of NGR-hTNF were larger in smaller tumours, which have less mature neovasculature. Soluble TNF receptors were released. CONCLUSIONS: The difficulty to find an optimal biological dose of NGR-TNF by DCE-MRI is likely caused by a combination of factors: (i) different profiles of early anti-vascular effects in tumours and healthy liver tissue, (ii) dependence of the magnitude of the anti-vascular effect of NGR-hTNF on tumour size and (iii) shedding kinetics of soluble TNF receptors.
M3 - SCORING: Zeitschriftenaufsatz
VL - 80
SP - 655
EP - 661
JO - EUR J RADIOL
JF - EUR J RADIOL
SN - 0720-048X
IS - 3
M1 - 3
ER -
