hyperpolarized c-13 pyruvate as a biomarker in patients with advanced solid tumor malignancies

Conditions: Prostate Cancer

Summary: this is a single center prospective imaging study investigating the utility of hyperpolarized c-13 pyruvate as a biomarker of pi3k/mtor pathway inhibition in patients with advanced solid tumor malignancies. the current protocol will serve as a companion imaging biomarker study paired with therapeutic trials of pi3k/mtor pathway inhibitors (e.g. cudc-907, byl719), as well as a stand-alone protocol for patients treated with standard-of-care therapies inhibiting the pi3k/mtor signaling pathway (eg. everolimus).

this is a single center prospective imaging study investigating the utility of hyperpolarized c-13 pyruvate/metabolic magnetic resonance (mr) imaging. the current protocol will serve as a companion imaging biomarker study paired with therapeutic trials of pi3k/mtor pathway inhibitors (e.g. cudc-907, byl719), as well as a stand-alone protocol for patients treated with standard-of-care therapies inhibiting the pi3k/mtor signaling pathway (eg. everolimus). in part a (run-in feasibility phase), patients will undergo imaging at a single time point, without paired tumor biopsy. there will be no follow up imaging or requirement for treatment with pi3k/mtor pathway inhibitor. iterative adjustment of radiofrequency coil geometry and imaging sequences will be undertaken to optimize intra-tumoral hyperpolarized pyruvate/lactate signal-to-noise ratio. in part b, patients will undergo paired baseline hyperpolarized c-13 pyruvate imaging + tumor biopsy,then initiate treatment with agent inhibiting the pi3k/mtor pathway. after 21 days (+/- 14 days), patients will undergo repeat hyperpolarized c-13 pyruvate mr imaging + tumor biopsy. patients will subsequently be treated with pi3k/mtor pathway inhibitor until disease progression, unacceptable toxicity, or patient/physician decision to discontinue therapy.

Eligibility criteria:
inclusion criteria: * presence of at least one target liver or other intra-abdominal lesion detected by standard staging scans that, in the judgment of study investigators, would be amenable to hyperpolarized c-13 pyruvate/metabolic mr imaging: target lesion must measure \>=1.0 cm in long axis diameter on ct or mri * the subject is able and willing to comply with study procedures and provide signed and dated informed consent. * eastern cooperative oncology group (ecog) performance status of 0 or 1. * adequate organ function, including creatinine \ =500 ml/min (by the cockcroft gault equation) and total bilirubin \<3x upper limit of normal (uln). part b only: * no prior local therapy to target lesion. * if patient agrees to optional biopsy: * presence of at least one target lesion amenable to percutaneous tumor biopsy in the judgment of interventional radiology * no history of bleeding diathesis. * patients on anti-coagulation they must be able to safely stop treatment for purposes of tumor biopsy. * planned treatment with agent targeting pi3k/mtor pathway (either standard of care or investigational agent) exclusion criteria: * patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent. * patients unwilling or unable to undergo mr imaging, including patients with contra-indications to mri, such as cardiac pacemakers or non-compatible intracranial vascular clips. * metallic implant or device that distorts local magnetic field and compromises the quality of mr imaging. * poorly controlled hypertension, defined as systolic blood pressure at study entry greater than 160 mm hg or diastolic blood pressure greater than 100 mm hg. the addition of anti-hypertensives to control blood pressure is allowed. * congestive heart failure or new york heart association (nyha) status ≥ 2. * a history of clinically significant ekg abnormalities, including qt prolongation (qtcf \> 500 ms), a family history of prolonged qt interval syndrome, or myocardial infarction (mi) within 6 months of study entry. patients with rate-controlled atrial fibrillation/flutter will be allowed on study. * any condition that, in the opinion of the principal investigator, would impair the patient's ability to comply with study procedures.