Low cost, high temporal resolution optical fiber-based γ-photon sensor for real-time pre-clinical evaluation of cancer-targeting radiopharmaceuticals.

Cancer radiopharmaceutical therapies (RPTs) have demonstrated great promise in the treatment of neuroendocrine and prostate cancer, giving hope to late-stage metastatic cancer patients with currently very few treatment options. These therapies have sparked a large amount of interest in pre-clinical research due to their ability to target metastatic disease, with many research efforts focused towards developing and evaluating targeted RPTs for different cancer types in in vivo models. Here we describe a method for monitoring real-time in vivo binding kinetics for the pre-clinical evaluation of cancer RPTs. Recognizing the significant heterogeneity in biodistribution of RPTs among even genetically identical animal models, this approach offers long-term monitoring of the same in vivo organism without euthanasia in contrast to ex vivo tissue dosimetry, while providing high temporal resolution with a low-cost, easily assembled platform, that is not present in small-animal SPECT/CTs. The method utilizes the developed optical fiber-based γ-photon biosensor, characterized to have a wide linear dynamic range with Lutetium-177 (177Lu) activity (0.5-500 µCi/mL), a common radioisotope used in cancer RPT. The probe's ability to track in vivo uptake relative to SPECT/CT and ex vivo dosimetry techniques was verified by administering 177Lu-PSMA-617 to mouse models bearing human prostate cancer tumors (PC3-PIP, PC3-flu). With this method for monitoring RPT uptake, it is possible to evaluate changes in tissue uptake at temporal resolutions <1 min to determine RPT biodistribution in pre-clinical models and better understand dose relationships with tumor ablation, toxicity, and recurrence when attempting to move therapies towards clinical trial validation.

A Method and Analysis to Enable Efficient Piezoelectric Transducer-Based Ultrasonic Power and Data Links for Miniaturized Implantable Medical Devices.

Acoustic links for implantable medical devices (implants) have gained attention primarily because they provide a route to wireless deep-tissue systems. The miniaturization of the implants is a key research goal in these efforts, nominally because smaller implants result in less acute tissue damage. Implant size in most acoustic systems is limited by the piezoelectric bulk crystal used for power harvesting and data communication. Further miniaturization of the piezocrystal can degrade system power transfer efficiency and data transfer reliability. Here, we present a new method for packaging the implant piezocrystal; the method maximizes power transfer efficiency ( η ) from the acoustic power at the piezo surface to the power delivered to the electrical load and information transfer across the acoustic link. Our method relies on placing piezo-to-substrate anchors to the piezo regions where the vibrational displacement of the mode of interest is zero. To evaluate our method, we investigated packaged 1×1×1 mm3 piezocrystals assembled with different sized anchors. Our results show that reducing the anchor size decreases anchor loss and thus improves piezo quality factor (Q). We also demonstrate that this method improves system electromechanical coupling. A strongly coupled, high-Q piezo with properly sized and located anchors is demonstrated to achieve significantly higher η and superior data transfer capability at resonance. Overall, this work provides an analysis and generic method for packaging the implant piezocrystal that enables the design of efficient acoustic power and data links, which provides a path toward the further miniaturization of ultrasonic implants to submillimeter scales.