Preclinical Pharmacokinetic and Safety Studies of Copper-Diacetyl-Bis(N-Methylthiosemicarbazone) (Cu-ATSM): Translational Studies for Internal Radiotherapy.

Hypoxia plays important roles in the prognosis of malignant brain tumors such as glioblastoma because it causes drug delivery deficiencies and the induction of hypoxia-inducible factor-1α in tumor cells. Extensive hypoxic areas are associated with poor prognosis of these fatal diseases. We previously reported that multiple administrations of the hypoxia-targeted internal radiotherapy agent Cu-diacetyl-bis(N-methylthiosemicarbazone) (Cu-ATSM), four times at intervals of 1 or 2 weeks, show antitumor effects in glioblastoma without treatment-related adverse events.

Assessment of Amino Acid/Drug Transporters for Renal Transport of [F]Fluciclovine (anti-[F]FACBC) in Vitro.

[F]Fluciclovine (-1-amino-3-[F]fluorocyclobutanecarboxylic acid; -[F]FACBC), a positron emission tomography tracer used for the diagnosis of recurrent prostate cancer, is transported via amino acid transporters (AATs) with high affinity (: 97-230 μM). However, the mechanism underlying urinary excretion is unknown. In this study, we investigated the involvement of AATs and drug transporters in renal [F]fluciclovine reuptake.

Amino acid PET tracers are reliable markers of treatment responses to single-agent or combination therapies including temozolomide, interferon-β, and/or bevacizumab for glioblastoma.

Introduction: We examined whether the amino acid PET tracers, trans-1-amino-3-(18)F-fluorocyclobutanecarboxylic acid (anti-(18)F-FACBC) and (11)C-methyl-l-methionine ((11)C-Met), are suitable for detecting early responses to combination therapies including temozolomide (TMZ), interferon-β (IFN), and bevacizumab (Bev) in glioblastoma.

Methods: Human glioblastoma U87MG (U87) cells were incubated with low dose TMZ to induce chemoresistance. Both trans-1-amino-3-fluoro-1-(14)C-cyclobutanecarboxylic acid (anti-(14)C-FACBC) and (3)H-methyl-l-methionine ((3)H-Met) uptake were quantified using triple-label accumulation assays to examine the relationship between tracer uptake and proliferation ((3)H-thymidine (TdR) accumulation) in vitro.

Trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid (anti-18F-FACBC) is a feasible alternative to 11C-methyl-L-methionine and magnetic resonance imaging for monitoring treatment response in gliomas.

Introduction: Amino acid PET tracers are promising for visualizing gliomas and evaluating radiochemotherapeutic effects. We compared the glioma detection and early response assessment utility between trans-1-amino-3-fluoro-1-(14)C-cyclobutanecarboxylic acid (anti-(14)C-FACBC) and (3)H-methyl-l-methionine ((3)H-Met) by simultaneously analyzing their uptake by rat gliomas treated with and without temozolomide (TMZ) in vitro and in vivo.

Methods: C6 rat gliomas were incubated with low-dose TMZ to induce chemoresistance.