RT Journal Article SR Electronic T1 Quantitative imaging of microscopic distributions of Actinium-225-PSMA in a murine model for dosimetry at the cellular level JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 242369 OP 242369 VO 65 IS supplement 2 A1 Martin, Isabella A1 Ansel, Clara A1 Wurzer, Alexander A1 Miller, Cassandra A1 D'Alessandria, Calogero A1 Kasch, Kay-Uwe A1 Rahmim, Arman A1 Benard, Francois A1 Uribe, Carlos A1 Brosch-Lenz, Julia YR 2024 UL http://jnm.snmjournals.org/content/65/supplement_2/242369.abstract AB 242369 Introduction: Radiopharmaceuticals that target the prostate-specific membrane antigen (PSMA) have gained increasing interest due to their favorable therapy response and have led to the successful approval of 177Lu-PSMA-617, a beta-emitting radiopharmaceutical. Novel radiopharmaceuticals labeled with alpha emitters have the potential to be even more potent due to their high linear energy transfer. However, this presents a new challenge as alpha particles can cause serious healthy tissue damage. It is crucial to understand the deposition of absorbed dose in tissue to gain insight into its effects. In the case of alpha particles, this deposition takes place within a highly limited range on the order of micrometers. The aim of this work was to generate quantitative images of microscopic distributions of 225Ac-PSMA in a murine model for micro-dosimetry to analyze distributions in kidney, tumor, and salivary gland tissue. Methods: LNCaP tumor-bearing mice were injected with 225Ac-PSMA-I&T and euthanized at 0.2h, 1h, 5h, 24h, and 168h post injection. Using an iQID alpha camera that captures individual alpha decays via a scintillation mechanism, 10µm slices of mice kidneys, salivary glands, and tumors from each time point were imaged for 20-48h. This imaging time provided high enough counting statistics to obtain clear images of the 225Ac-PSMA-I&T distributions. The 225Ac alpha detection efficiency of the iQID camera was tested with pixel (PT) and cluster (CT) thresholds chosen for best image quality. Pixel threshold is a minimum value for a pixel to be counted towards the cluster threshold, which is the number of pixels which must be detected for an event to be recorded. To convert the images from counts to activity values, we determined calibration factors by placing the same slide in a gamma counter and relating the count rate in the iQID image with the activity obtained from the gamma counter. The activity images were decay corrected to the euthanization time and convolved with simulated dose-point kernels to generate dose-rate images.Results: We determined that the PT and CT thresholds providing clearest images were 20 and 2, respectively. Calibration factors ranged from 0.1 to 5.1 Bq/cps. We were not able to obtain calibration factors for the 168h images due to the low activity which was not detectable in the gamma counter. For the kidneys (K), the uptake was distributed mainly on the outer regions (i.e., outer stripe of the outer medulla and cortex). The uptake within the salivary glands (SG) and tumors (T) was more uniformly distributed. The highest measured absorbed doses in the imaged 10 µm slices were K24h= 3.5x10-5±1.8x10-4 mGy/s, SG24h= 5.5x10-5±2.7x10-3 mGy/s, and T1h= 1.7x10-4±7.9x10-4 mGy/s.Conclusions: We were successful in generating quantitative 2D activity images from raw images of 225Ac-PSMA-I&T using the iQID alpha camera. It is important to note that the calibration factor for conversion from detected count rate to activity values varies with the imaging slice and should be cross-calibrated with a gamma counter. Images showed heterogenous dose distributions in the kidneys with accumulation mainly in the outer tissue layers while doses were more homogeneous in tumors and salivary glands. This imaging methodology, combined with mice whole-organ biodistribution data (i.e. washout information) and the dose rate images, can be used to generate absorbed dose distributions at the micro-level. Next steps include studying correlations of absorbed dose and biological effects at this micrometer scale to better guide radiopharmaceutical therapies with alpha emitters.