Evaluation of early response to SU101 target-based therapy in patients with recurrent supratentorial malignant gliomas using FDG PET and Gd-DTPA MRI.
Changes in [18F]-2-fluoro-2-deoxyglucose (FDG) uptake and gadopentetate dimeglumine (Gd-DTPA) enhancement before and after the first course of treatment with a cytostatic agent SU101 (N-[(4-trifluoromethyl)-phenyl]-5-methylisoxazole-4-carboxamide, SUGEN) were assessed using positron emission tomography (PET) and magnetic resonance imaging (MRI) in a pilot study of 8 patients with recurrent supratentorial malignant gliomas. The localization and the volume of Gd-DTPA enhancement and FDG hypermetabolism were analyzed. PET and MRI studies were performed one week before and 7.6+/-3.7 weeks after administration of SU101. The ratios of mean tumor activity to mean contralateral white matter and ipsilateral cerebellar activity were calculated for tumor regions, and SUV values corrected to the subjects' body surface area and glucose level (SUVbsa*glu) were calculated for nontumor regions. Five patients had a substantial increase of tumor volume on both PET and MRI during the first course of SU101. PET and MRI showed roughly equivalent volume changes. Large tumor volume increases were associated with a short time to clinical progression. The metabolic change in the tumor following the first course of SU101 varied from patient to patient, ranging from a 31% reduction to a 43% increase in FDG uptake ratio. Changes in FDG uptake were not predictive of time to progression or survival. In 2 patients with marked clinical deterioration and rapid tumor growth, there were differences in localization of Gd-DTPA enhancement and FDG hypermetabolism suggesting that hypermetabolism beyond the area of contrast enhancement may be of value in predicting rapid progression of high-grade glioma. SU101 did not induce any appreciable changes in SUVbsa*glu for non-tumor brain in 6 of 8 patients.
Vlassenko
A G
AG
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Thiessen
B
B
Beattie
B J
BJ
Malkin
M G
MG
Blasberg
R G
RG
D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001254:Astrocytoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D001693:Biological Transport, Active / Q000187:drug effects; D002330:Carmustine / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D018450:Disease Progression; D018572:Disease-Free Survival; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D019788:Fluorodeoxyglucose F18; D019786:Gadolinium DTPA; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077339:Leflunomide; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D011379:Prognosis; D015398:Signal Transduction / Q000187:drug effects; D015173:Supratentorial Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007555:Isoxazoles; D010982:Platelet-Derived Growth Factor; D019788:Fluorodeoxyglucose F18; D000077339:Leflunomide; D005947:Glucose; D019786:Gadolinium DTPA; D002330:Carmustine