{
  "abstract": "Background MRI, CT, and PET imaging of therapeutic response is limited to a single biomarker with millimeter resolution at month-long intervals. Thus, the complex interplay between drugs, cancer, and the immune system responsible for the wide variations in response to immunotherapy remains largely opaque. 1 2 Alternatively, fluorescence imaging could capture multiple biomarkers with cellular resolution in real-time,3 but scattering limits the penetration of even near-infrared light to a centimeter in tissue.4 Therefore, we present a miniaturized, implantable fluorescence imager, enabling dynamic molecular imaging from inside the body. As a proof-of-concept of in vivo imaging, the sensor captures the biodistribution of Herceptin (trastuzumab)—a targeted therapy for HER2+ tumors5—in murine breast cancer models.Methods Our implant harnesses several technologies for miniaturization ( figure 1A). On-implant micro-laser-diodes excite the fluorophores and the fluorescence is captured through a 520-mm-thick optical frontend, capable of imaging 3 different fluorophores at 125 mm resolution.6 A 5 × 2.5 mm2 CMOS chip (IC) integrates the image sensor, power harvester, laser driver, and control system. While the IC is capable of wireless operation via ultrasound,7 a wired connection is used in this study. The implant is fabricated on a flexible printed circuit board (PCB), coated with parylene C for biocompatibility (figure 1B).For in vivo imaging, HCC1569 (HER2+) and MCF-7 (HER2−) breast cancer xenografts are grown for 2 weeks in nude mice. Sterile devices are then surgically implanted above the tumors (figure 1C) for each model. Six additional mice are used for imaging with a Revvity IVIS Spectrum. The mice are injected with 0.6 nmol of Herceptin conjugated to Alexa Fluor 647. At given times points, the mice are anesthetized and the implants are connected to a reader for imaging (figure 1D). Reference images are taken with the IVIS.Results The raw sensor images in figure 1E show that fluorescence in the HER2+ tumor increases significantly over 24 hours, consistent with Herceptin binding. In figure 1F, the mean pixel value from the implants plotted over time shows that the fluorescence in the HER2− tumor is markedly less. These trends are confirmed by the IVIS (figure 1G).Conclusions While we show real-time in vivo imaging of Herceptin biodistribution, this can be exchanged for an immunotherapeutic or immune biomarker and expanded to multiple markers through multiplexed imaging.6 Combined with wireless operation,7 8 our device could enable a ‘continuous biopsy’ of response to immunotherapy.Acknowledgements This work was supported the Office of the Director and the National Institute of Dental and Craniofacial Research of the National Institutes of Health under Award DP2DE030713 and in part by the John V. Carbone Jr. Pancreatic Cancer Research Memorial Fund and the Zaidi Family Gift Fund.References Nishino M, Hatabu H, Hodi FS. Imaging of cancer immunotherapy: Current approaches and future directions. Radiology. 2019;290;9–22.Unterrainer M, et al. PET/CT imaging for tumour response assessment to immunotherapy: current status and future directions. Eur. Radiol. Exp., 2020 Dec;4(1).Liu J, Cheng P, Xu C, Pu K. Molecular probes for in vivo optical imaging of immune cells. Nat. Biomed. Eng. 2025;1–20.Owens EA, Lee S, Choi J, Henary M, Choi HS. NIR fluorescent small molecules for intraoperative imaging. WIREs Nanomedicine Nanobiotechnology. 2015;7;828–838.Nahta R, Esteva FJ. Herceptin: mechanisms of action and resistance. Cancer Lett. 2006;232;123–138.Roschelle M, et al. Multicolor fluorescence microscopy for surgical guidance using a chip-scale imager with a low-NA fiber optic plate and a multi-bandpass interference filter. Biomed. Opt. Express. 2024;15;1761.Roschelle M, et al. A wireless, multicolor fluorescence image sensor implant for real-time monitoring in cancer therapy. IEEE J. Solid-State Circuits. 2024;1–19.Rabbani R, et al. Towards a wireless image sensor for real-time fluorescence microscopy in cancer therapy. IEEE Trans. Biomed. Circuits Syst. 2024;1–15.Ethics Approval This study was approved by the University of California San Francisco Institutional Animal Care and Use Committee (IACUC) under approval number AN193898-01C.Abstract 96 Figure 1A. 3D model of implant B. Fabricated implant. C. Post-operative mouse. D. Imaging setup. E. Raw implant images the HER+ tumor. F. Implant imaging time course. G. IVIS imaging time course",
  "authors": [
    {
      "affiliations": [
        "University of California, San Francisco, San Francisco, CA, USA",
        "University of California, Berkeley, Berkeley, CA, USA"
      ],
      "name": "Micah Roschelle"
    },
    {
      "affiliations": [
        "University of California, San Francisco, San Francisco, CA, USA"
      ],
      "name": "Abijeet Mehta"
    },
    {
      "affiliations": [
        "University of California, San Francisco, San Francisco, CA, USA"
      ],
      "name": "Jack Bartley"
    },
    {
      "affiliations": [
        "University of California, Berkeley, Berkeley, CA, USA"
      ],
      "name": "Rozhan Rabbani"
    },
    {
      "affiliations": [
        "University of California, Berkeley, Berkeley, CA, USA"
      ],
      "name": "Longhui Qiu"
    },
    {
      "affiliations": [
        "University of California, San Francisco, San Francisco, CA, USA"
      ],
      "name": "Hui Zhang"
    },
    {
      "affiliations": [
        "University of California, San Francisco, San Francisco, CA, USA"
      ],
      "name": "Juan Antonio Camara Serrano"
    },
    {
      "affiliations": [
        "University of California, San Francisco, San Francisco, CA, USA"
      ],
      "name": "Shih-Wei Chuo"
    },
    {
      "affiliations": [
        "University of California, San Francisco, San Francisco, CA, USA"
      ],
      "name": "Charles Craik"
    },
    {
      "affiliations": [
        "University of California, Berkeley, Berkeley, CA, USA"
      ],
      "name": "Ali Niknejad"
    },
    {
      "affiliations": [
        "University of California, San Francisco, San Francisco, CA, USA"
      ],
      "name": "Mekhail Anwar"
    }
  ],
  "title": "96 Real-time in vivo imaging of therapeutic biodistribution with a miniaturized, implantable fluorescence imager",
  "uid": "54b7e4d3-c614-5c61-ac07-53256f107836"
}