Radiopharmaceutical Delivery for Theranostics: Pharmacokinetics and Pharmacodynamics.

Theranostics is a new and evolving combination diagnostic and/or therapeutic approach that is demonstrating efficacy for treatment of a growing number of cancers. In this approach, a diagnostic radiopharmaceutical is used in concert with positron-emission tomography (PET) or single photon emission computed tomography (SPECT) imaging to identify whether a cancer-specific membrane protein is strongly expressed on a patient's tumors. If the molecular target is detected with sufficient specificity and uptake, a therapeutic radiopharmaceutical, nearly identical to the diagnostic radiopharmaceutical except labeled with a longer-lived alpha or beta-emitting radionuclide, is administered at a therapeutic dose level to treat the cancer. Quantitative imaging methods are being used to elucidate patient-specific pharmacokinetics to select patients for whom the therapeutic radiopharmaceutical would be most beneficial. Similarly, quantitative imaging of the therapeutic radionuclide is being used to image pharmacodynamic response to therapy (cell kill) to guide personalized, patient-specific dosages designed to both reduce radiation toxicities and optimize radiotherapeutic benefit.

Effects of chronic marijuana use on brain activity during monetary decision-making.

Marijuana (MJ) acutely acts on cannabinoid receptors that are found in numerous brain regions, including those involved in reward processing and decision-making. However, it remains unclear how long-term, chronic MJ use alters reward-based decision-making. In the present study, using [(15)O]water PET imaging, we measured brain activity in chronic MJ users, who underwent monitored abstinence from MJ for approximately 24 h before imaging, and control participants, while they took part in the Iowa Gambling Task (IGT), a monetary decision making task that strongly relies on the ventromedial prefrontal cortex (vmPFC). During PET imaging, participants took part in the standard and a variant version of the IGT as well as a control task. Chronic MJ users performed equally well on the standard IGT, but significantly worse than controls on the variant IGT. Chronic MJ users and control subjects showed increased regional cerebral blood flow (rCBF) in the vmPFC on both versions of the IGT compared to the control task. In the two-group comparison, chronic MJ users showed significantly greater rCBF than controls in the vmPFC on the standard IGT and greater activity in the cerebellum on both versions of the IGT. Furthermore, duration of use, but not age of first use, was associated with greater activity in the vmPFC. Thus, chronic MJ users tend to strongly recruit neural circuitry involved in decision-making and reward processing (vmPFC), and probabilistic learning (cerebellum) when performing the IGT.