Purpose Radiolabelled somatostatin analogues targeting somatostatin receptors (SSR) are well established for combined positron emission tomography/computer tomography (PET/CT) imaging of neuroendocrine tumours (NET). [18F]SiTATE has recently been introduced showing high image quality, promising clinical performance and improved logistics compared to the clinical reference standard 68Ga-DOTA-TOC. Here we present the first dosimetry and optimal scan time analysis. Methods Eight NET patients received a [18F]SiTATE-PET/CT (250 ± 66 MBq) with repeated emission scans (10, 30, 60, 120, 180 min after injection). Biodistribution in normal organs and SSR-positive tumour uptake were assessed. Dosimetry estimates for risk organs were determined using a combined linear-monoexponential model, and by applying 18F S-values and reference target masses for the ICRP89 adult male or female (OLINDA 2.0). Tumour-to-background ratios were compared quantitatively and visually between different scan times. Results After 1 h, normal organs showed similar tracer uptake with only negligible changes until 3 h post-injection. In contrast, tracer uptake by tumours increased progressively for almost all types of metastases, thus increasing tumour-to-background ratios over time. Dosimetry resulted in a total effective dose of 0.015 ± 0.004 mSv/MBq. Visual evaluation revealed no clinically relevant discrepancies between later scan times, but image quality was rated highest in 60 and 120 min images. Conclusion [18F]SiTATE-PET/CT in NET shows overall high tumour-to-background ratios from 60 to 180 min after injection and an effective dose comparable to 68Ga-labelled alternatives. For clinical use of [18F]SiTATE, the best compromise between image quality and tumour-to-background contrast is reached at 120 min, followed by 60 min after injection.
Background: Dosimetry can tailor prostate-specific membrane-antigen-targeted radioligand therapy (PSMA-RLT) for metastatic castration-resistant prostate cancer (mCRPC). However, whole-body tumor dosimetry is challenging in patients with a high tumor burden. We evaluate a simplified index-lesion-based single-photon emission computed tomography (SPECT) dosimetry method in correlation with clinical outcome. Methods: 30 mCRPC patients were included (median 71 years). The dosimetry was performed for the first cycle using quantitative 177Lu-SPECT. The response was evaluated using RECIST 1.1 and PERCIST criteria, as well as changes in PSMA-positive tumor volume (PSMA-TV) in post-therapy PSMA-PET and biochemical response according to PSA changes after two RLT cycles. Results: Mean tumor doses as well as index-lesion doses were significantly higher in PERCIST responders compared to non-responders (10.2 ± 12.0 Gy/GBq vs. 4.0 ± 2.9 Gy/GBq, p = 0.03 and 13.7 ± 14.2 Gy/GBq vs. 5.9 ± 4.4 Gy/GBq, p = 0.04, respectively). No significant differences in mean tumor and index lesion doses were observed between responders and non-responders according to RECIST 1.1, PSMA-TV, and biochemical response criteria. Conclusion: Compared to mean tumor doses on a patient level, single index-lesion-based SPECT dosimetry correlates equally well with the response to PSMA-RLT according to PERCIST criteria and may represent a fast and feasible dosimetry approach for clinical routine.
Radiopharmaceutical therapies (RPTs) with Lutetium-177 prostate-specific membrane antigen (PSMA) ligands have demonstrated promising results for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The lack of absorbed dose and effect relationships currently prevents from patientspecific activity personalization. To ease the implementation of dosimetry in routine clinic workflow of RPT, simplified methods such as single time point (STP) instead of multiple time point (MTP) imaging protocols are required. This work aims at assessing differences in time-integrated activity (TIA) of STP versus MTP image-based dosimetry for 177 Lu-PSMA-617 therapy. Methods: 20 mCRPC patients with MTP quantitative 177 Lu-SPECT imaging data (~24h, 48h, 72h post administration) available on first and second 177 Lu-PSMA-617 therapy cycles were included in this study. Time-activity-curves were fitted for kidneys and lesions to derive effective half-lives and yield reference TIA. STP approaches involved the formula by Hänscheid (STP H ) and a prior information method (STP prior ) that uses the effective half-lives from the first therapy cycle. All time points were considered for the STP approaches. Percentage differences (PD) in TIA between STP and MTP was compared for the second therapy cycle. Results: Using STP H at 48h p.i. for the kidneys had -1.3±5.6% difference against MTP, while STP prior showed a PD of 4.6±6.2%. Smallest average 3 differences for the 56 investigated individual lesions were found using the STP prior approach at 48h p.i. with only 0.4±14.9%, while STP H at 72h p.i. had smallest PD of -1.9±14.8%. Conclusion: STP dosimetry for 177 Lu-PSMA-617 therapy using a single SPECT/CT at 48h or 72h is feasible with a difference of <±20% compared against MTP. Both, STP H and STP prior have demonstrated their validity. We believe this finding can increase the adoption of dosimetry and facilitate implementation in routine clinical RPT workflows. Doing so will ultimately enable the finding of dose-effective relationships based on fixed therapy activities that could in future allow for absorbed dose based RPT activity personalization.
Background: Red blood cells (RBC) scintigraphy can be used not only for detection of bleeding sites, but also of spleen tissue. However, there is no established quantitative readout. Therefore, we investigated uptake in suspected splenic lesions in direct quantitative correlation to sites of physiologic uptake in order to objectify the readout. Methods: 20 patients with Tc-99m-labelled RBC scintigraphy and SPECT/low-dose CT for assessment of suspected splenic tissue were included. Lesions were rated as vital splenic or non-splenic tissue, and uptake and physiologic uptake of bone marrow, pancreas, and spleen were then quantified using a volume-of-interest based approach. Hepatic uptake served as a reference. Results: The median uptake ratio was significantly higher in splenic (2.82 (range, 0.58–24.10), n = 47) compared to other lesions (0.49 (0.01–0.83), n = 7), p < 0.001, and 5 lesions were newly discovered. The median pancreatic uptake was 0.09 (range 0.03–0.67), bone marrow 0.17 (0.03–0.45), and orthotopic spleen 14.45 (3.04–29.82). Compared to orthotopic spleens, the pancreas showed lowest uptake (0.09 vs. 14.45, p = 0.004). Based on pancreatic uptake we defined a cutoff (0.75) to distinguish splenic from other tissues. Conclusion: As the uptake in extra-splenic regions is invariably low compared to splenules, it can be used as comparator for evaluating suspected splenic tissues.
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