Rahul Lall

EECS Department, University of California, Berkeley

Technical Report No. UCB/

May 1, 2025

Radiopharmaceutical therapy (RPT) utilizes tumor-specific small molecules, antibodies, and derivatives thereof, conjugated to radioisotopes to systemically target cancer cells while sparing most normal tissues. Typically, the conjugated radioisotope is a β- or α-particle emitter, that provides localized dose to the target lesion, with additional γ photon decay chains that are often used for imaging over the course of the therapy. RPT has shown great promise in the treatment of neuroendocrine and metastatic prostate cancer, but delivering optimal radiation dose to tumors while minimizing dose to organs-at-risk (OAR) remains an unmet need due to significant patient-to-patient heterogeneity in treatment response. Single time point imaging (mostly single photon emission computed tomography (SPECT))-based dosimetry offers a snapshot of the body-wide activity distribution at a given time point, but even single SPECT imaging is generally limited in availability and not applicable to many types of RPT, often leading to significant inaccuracies in estimating total integrated dose. Therefore, multiple snapshots of the in vivo activity distribution are needed to accurately calculate total integrated dose and inform therapeutic modulations to personalize the therapy for each patient.

Towards this goal, this work presents a novel wearable system composed of a sparse network of uncollimated, mm-scale γ photon sensing chips to enable continuous, real-time activity reconstruction in RPT. Each of the mm-scale γ photon sensors are 3×3.3 mm application specific integrated circuits (ASIC) implemented in monolithic 180 nm CMOS, and capable of direct detection of single γ photons and their incident energy. A new high-temporal resolution, activity reconstruction method was developed to use these uncollimated sensor network readings along with a priori information from pretherapy imaging to reconstruct the activity in all the tumors and OAR. The ASICs were characterized under a therapeutic orthovoltage X-ray beam and with numerous radioisotopes used in RPT, and the reconstruction system was successfully validated on in vivo human prostate cancer mouse xenografts and on human-scale torso phantoms. Through a better understanding of optimal dose management, it is envisioned that the developed system will allow for personalization of RPT and improvement in treatment response.

Advisors: Ali Niknejad and Mekhail Anwar

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BibTeX citation:

@phdthesis{Lall:31720,
    Author= {Lall, Rahul},
    Editor= {Anwar, Mekhail and Niknejad, Ali and Abergel, Rebecca and Chien, Jun-Chau},
    Title= {Wearable, Integrated Sparse-SPECT for Continuous, Real-Time Dosimetry in Cancer Radiopharmaceutical Therapy},
    School= {EECS Department, University of California, Berkeley},
    Year= {2025},
    Number= {UCB/},
    Abstract= {Radiopharmaceutical therapy (RPT) utilizes tumor-specific small molecules, antibodies, and derivatives thereof, conjugated to radioisotopes to systemically target cancer cells while sparing most normal tissues. Typically, the conjugated radioisotope is a β- or α-particle emitter, that provides localized dose to the target lesion, with additional γ photon decay chains that are often used for imaging over the course of the therapy. RPT has shown great promise in the treatment of neuroendocrine and metastatic prostate cancer, but delivering optimal radiation dose to tumors while minimizing dose to organs-at-risk (OAR) remains an unmet need due to significant patient-to-patient heterogeneity in treatment response. Single time point imaging (mostly single photon emission computed tomography (SPECT))-based dosimetry offers a snapshot of the body-wide activity distribution at a given time point, but even single SPECT imaging is generally limited in availability and not applicable to many types of RPT, often leading to significant inaccuracies in estimating total integrated dose. Therefore, multiple snapshots of the in vivo activity distribution are needed to accurately calculate total integrated dose and inform therapeutic modulations to personalize the therapy for each patient. 

Towards this goal, this work presents a novel wearable system composed of a sparse network of uncollimated, mm-scale γ photon sensing chips to enable continuous, real-time activity reconstruction in RPT. Each of the mm-scale γ photon sensors are 3×3.3 mm application specific integrated circuits (ASIC) implemented in monolithic 180 nm CMOS, and capable of direct detection of single γ photons and their incident energy. A new high-temporal resolution, activity reconstruction method was developed to use these uncollimated sensor network readings along with a priori information from pretherapy imaging to reconstruct the activity in all the tumors and OAR. The ASICs were characterized under a therapeutic orthovoltage X-ray beam and with numerous radioisotopes used in RPT, and the reconstruction system was successfully validated on in vivo human prostate cancer mouse xenografts and on human-scale torso phantoms. Through a better understanding of optimal dose management, it is envisioned that the developed system will allow for personalization of RPT and improvement in treatment response.},
}

EndNote citation:

%0 Thesis
%A Lall, Rahul 
%E Anwar, Mekhail 
%E Niknejad, Ali 
%E Abergel, Rebecca 
%E Chien, Jun-Chau 
%T Wearable, Integrated Sparse-SPECT for Continuous, Real-Time Dosimetry in Cancer Radiopharmaceutical Therapy
%I EECS Department, University of California, Berkeley
%D 2025
%8 May 1
%@ UCB/
%F Lall:31720