Whole-body Planar Imaging Research Articles

Prediction of 1cm dose-equivalent rate on the day after administration of 177Lu-DOTATATE from 111In-somatostatine receptor scintigraphy prior to treatment.

When patients administered 177Lu-DOTATATE are released or discharged from rooms where radiopharmaceuticals are used, the time required for release or discharge varies across patients. This study investigated whether the amount of radioactivity accumulated on 111In-somatostatine receptor scintigraphy (111In-SRS) performed prior to treatment can predict the 1cm dose-equivalent rate at a distance of 1m from the patient on the day after 177Lu-DOTATATE administration. Whole-body planar 111In-SRS images were acquired for 21 patients. Pixel values within whole-body and abdominal (35 × 25cm) regions of interest (ROIs) were converted to radioactivity dose (MBq). The 1cm dose-equivalent rate (µSv/h) at a distance of 1m from the patient 18.3 ± 0.5h after administration of 177Lu-DOTATATE was measured using an ionization survey meter. The following relationships were observed between the radioactivity on 111In-SRS and the 1cm dose-equivalent rate on the day after administration of 177Lu-DOTATATE: whole-body ROI: y = 0.16x + 5.01 (r = 0.56, p = 0.009), abdominal ROI: y = 0.27x + 5.13 (r = 0.63, p = 0.002). The regression equations indicate that patients cannot be released or discharged from the radiopharmaceutical room the day after 177Lu-DOTATATE administration if the whole-body and abdominal ROI doses are greater than 81 and 48MBq, respectively, on 111In-SRS. The amount of radioactivity accumulated on 111In-SRS may be a predictor of release criteria for patients receiving 177Lu-DOTATATE.

All that glitters is not gold: high uptake on PSMA PET in non-prostate cancers does not mean that treatment with [177Lu]Lu-PSMA-radioligand will be successful.

The main objective is to discuss why treatment of non-prostate cancers with [177Lu]Lu-PSMA-radioligand achieved only low tumor dose in most published cases, despite high uptake on PSMA PET. We use a patient with renal cell carcinoma as an illustrative example. Furthermore, we discuss how the problem with early washout and low tumor dose might be overcome by using a radionuclide with shorter half-life, matching the target binding residence time. [68Ga]Ga-PSMA-11 PET/CT of a 56-year old man with metastatic renal cell carcinoma showed high lesion uptake. One dose of 6.9 GBq [177Lu]Lu-PSMA-I&T was administrated. Post-therapy dosimetry was performed with SPECT/CT and whole-body planar imaging after 5, 24 and 48h. Doses to target lesions were only 0.2-0.5Gy. No treatment effect was achieved. Rapid tumor washout of [177Lu]Lu-PSMA-I&T and low tumor dose despite high uptake of [68Ga]Ga-PSMA-11 are most likely caused by localization of PSMA-receptors on neovasculature rather than on the tumor cells, and unlike in prostate cancer cells, the PSMA-RL / PSMA-receptor complex is not internalized. To overcome the problem with early washout, the use of a radionuclide with shorter half-life matching the target binding residence time will be needed.

EANM position paper on challenges and opportunities of full-ring 360° CZT bone imaging: it's time to let go of planar whole-body bone imaging.

The introduction of smaller footprint, more sensitive Cadmium-Zinc-Telluride (CZT)-based detectors with improved spatial and energy resolution has enabled the design of innovative full-ring 360° CZT SPECT/CT systems (e.g., VERITON® and StarGuide™). With this transformative technology now aiming to become mainstream in clinical practice, several critical questions need to be addressed. This EANM position paper provides practical recommendations on how to use these devices for routine bone SPECT/CT studies, facilitating the transition from traditional planar whole-body imaging and conventional SPECT/CT to these novel systems. In particular, initial guidance is provided on imaging acquisition and reporting workflows, image reconstruction, and CT acquisition parameters. Given the emerging nature of this technology, the available evidence base is still limited, and the proposed adaptations in workflows and scan protocols will likely evolve before being integrated into definitive guidelines. In the meantime, this EANM position paper serves as a comprehensive guide for integrating these advanced hybrid SPECT/CT imaging systems into clinical practice and outlining areas for further study.

Phase I Clinical Evaluation of Designed Ankyrin Repeat Protein [99mTc]Tc(CO)3-(HE)3-Ec1 for Visualization of EpCAM-Expressing Lung Cancer.

A high level of EpCAM overexpression in lung cancer makes this protein a promising target for targeted therapy. Radionuclide visualization of EpCAM expression would facilitate the selection of patients potentially benefiting from such treatment. Single-photon computed tomography (SPECT) using 99mTc-labeled engineered scaffold protein DARPin Ec1 has shown its effectiveness in imaging tumors with overexpression of EpCAM in preclinical studies, providing high contrast just a few hours after injection. This first-in-human study aimed to evaluate the safety and distribution of [99mTc]Tc(CO)3-(HE)3-Ec1 in patients with primary lung cancer. Twelve lung cancer patients were injected with 300.7 ± 103.2 MBq of [99mTc]Tc(CO)3-(HE)3-Ec1. Whole-body planar imaging (at 2, 4, 6 and 24 h after injection) and SPECT/CT of the lung (at 2, 4, and 6 h) were performed. The patients' vital signs and possible side effects were monitored up to 7 days after injection. The patients tolerated the injection of [99mTc]Tc(CO)3-(HE)3-Ec1 well, and their somatic condition remained normal during the entire follow-up period. There were no abnormalities in blood and urine tests after injection of [99mTc]Tc(CO)3-(HE)3-Ec1. The highest absorbed doses were in the kidneys, liver, pancreas, thyroid, gallbladder wall, and adrenals. There was also a relatively high accumulation of [99mTc]Tc(CO)3-(HE)3-Ec1 in the small and large intestines, pancreas and thyroid. According to the SPECT/CT, accumulation of [99mTc]Tc(CO)3-(HE)3-Ec1 in the lung tumor was found in all patients included in the study. Intensive accumulation of [99mTc]Tc(CO)3-(HE)3-Ec1 was also noted in regional metastases. [99mTc]Tc(CO)3-(HE)3-Ec1 can potentially be considered a diagnostic tracer for imaging EpCAM expression in lung cancer patients and other tumors with overexpression of EpCAM.

Comparative post-therapeutic dosimetry between 2D planar-based and hybrid-based methods for personalized Lu-177 treatment.

This study aims to compare the calculated absorbed dose in target organs and tumors obtained using the different imaging protocols and the calculation methodologies implemented by HERMES HybridViewer dosimetry software for 177Lu-PSMA I&T and 177Lu-DOTATATE therapy. Multiple time-point whole-body planar images and one SPECT/CT image were acquired from 18 patients including 177Lu-PSMA I&T (13 patients) and 177Lu-DOTATATE treatment (5 patients) after administration of 3.80-8.58GBq injected activity. The regions of interest were drawn in the whole body, kidneys, liver, urinary bladder, salivary glands, and tumors to determine the time-integrated activity (TIA) in source organs. Absorbed doses in target organs were calculated according to the Medical Internal Radiation Dose (MIRD) scheme using the HERMES HybridViewer dosimetry integrated with OLINDA/EXM V.2.1 that utilizes the non-uniform rational B-splines (NURBS) for computational digital phantom. The planar-based dosimetry showed a higher dose per injected activity compared to the hybrid-based dosimetry, primarily due to organ overlap. The highest difference in absorbed dose between the imaging scenarios was observed in the spleen with a variation of up to 51.6%, while the difference for other target organs and tumors was less than 40%. The dosimetry calculation derived from the 2D planar-based method consistently demonstrates a significantly higher absorbed dose in organs and tumors compared with the hybrid-based method. However, the hybrid method outperforms the planar method in terms of tumor visualization and overlap-free organ delineation.

Accuracy of patient-specific I-131 dosimetry using hybrid whole-body planar-SPECT/CT I-123 and I-131 imaging

PurposeThis study aimed to assess the accuracy of patient-specific absorbed dose calculations for tumours and organs at risk in radiopharmaceutical therapy planning, utilizing hybrid planar-SPECT/CT imaging.MethodsThree Monte Carlo (MC) simulated digital patient phantoms were created, with time-activity data for mIBG labelled to I-123 (LEHR and ME collimators) and I-131 (HE collimator). The study assessed the accuracy of the mean absorbed doses for I-131-mIBG therapy treatment planning. Multiple planar whole-body (WB) images were simulated (between 1 to 72 h post-injection (p.i)). The geometric-mean image of the anterior and posterior WB images was calculated, with scatter and attenuation corrections applied. Time-activity curves were created for regions of interest over the liver and two tumours (diameters: 3.0 cm and 5.0 cm) in the WB images. A corresponding SPECT study was simulated at 24 h p.i and reconstructed using the OS-EM algorithm, incorporating scatter, attenuation, collimator-detector response, septal scatter and penetration corrections. MC voxel-based absorbed dose rate calculations used two image sets, (i) the activity distribution represented by the SPECT images and (ii) the activity distribution from the SPECT images distributed uniformly within the volume of interest. Mean absorbed doses were calculated considering photon and charged particle emissions, and beta emissions only. True absorbed doses were calculated by MC voxel-based dosimetry of the known activity distributions for reference.ResultsConsidering photon and charged particle emissions, mean absorbed dose accuracies across all three radionuclide-collimator combinations of 3.8 ± 5.5% and 0.1 ± 0.9% (liver), 5.2 ± 10.0% and 4.3 ± 1.7% (3.0 cm tumour) and 15.0 ± 5.8% and 2.6 ± 0.6% (5.0 cm tumour) were obtained for image set (i) and (ii) respectively. Considering charged particle emissions, accuracies of 2.7 ± 4.1% and 5.7 ± 0.7% (liver), 3.2 ± 10.2% and 9.1 ± 1.7% (3.0 cm tumour) and 13.6 ± 5.7% and 7.0 ± 0.6% (5.0 cm tumour) were obtained for image set (i) and (ii) respectively.ConclusionThe hybrid WB planar-SPECT/CT method proved accurate for I-131-mIBG dosimetry, suggesting its potential for personalized treatment planning.

Clinical Internal Dosimetry and Biodistribution of 177 Lu-DOTA-Trastuzumab in HER2-Positive Metastatic and Locally Advanced Breast Carcinoma.

The aim of this study was to assess the biodistribution and dosimetry of 177 Lu-DOTA-trastuzumab in patients with HER2-positive breast carcinoma using whole-body (WB) planar imaging at multiple time points. This study was a prospective evaluation of HER2-positive metastatic/locally advanced breast carcinoma patients who underwent gamma camera imaging for dosimetry and biodistribution studies by using 177 Lu-DOTA-trastuzumab. The standard diagnostic dosimetry protocol was followed, which included cold trastuzumab injection followed by in-house produced 177 Lu-DOTA-trastuzumab. Serial WB planar images (anterior and posterior) were obtained on gamma camera after the infusion of 177 Lu-DOTA-trastuzumab at multiple time points. Whole-body and organ regions of interest were drawn, and the numbers of disintegrations were obtained. The mean absorbed doses for the liver, spleen, kidneys, heart, red marrow, and tumor were obtained from OLINDA EXM v2.1.1 and ORIGIN software. The study included a cohort of 21 female breast carcinoma patients. Tracer activity ( 177 Lu-DOTA-trastuzumab) was noted in the physiological organs such as the liver, spleen, kidneys, heart, as well as in the tumors. On visual analysis of 177 Lu-DOTA-trastuzumab biodistribution, the liver activity showed gradual clearance over time, and although spleen was comparatively faintly visualized than liver and similarly, kidneys were faintly visualized suggestive of the alternate route of tracer excretion. The maximum number of patients (n = 12) showed 2 components of clearance, namely, fast and slow. The average effective half-life of all the patients (including single and 2 components of clearance) was 106.25 ± 22.14 hours (84.11-128.39 hours). The mean absorbed dose for the liver, spleen, kidneys, heart, whole body, and red marrow was 1.0702 ± 0.731, 1.4114 ± 0.462, 1.4232 ± 0.364, 1.4719 ± 0.602, 0.2412 ± 0.0295, and 0.1485 ± 0.0213 mGy/MBq, respectively, by OLINDA EXM and 0.5741 ± 0.333, 0.8096 ± 0.224, 0.7943 ± 0.235, 1.8971 ± 0.713, and 0.09619 ± 0.0144 for liver, spleen, kidneys, heart and whole body respectively by ORIGIN. The absorbed radiation dose for tumor was 1.94E+2 by OLINDA EXM software and 1.78E+2 by ORIGIN software. In this study, during and after infusion of 177 Lu-DOTA-trastuzumab, no major adverse effects were noted in any patient except 1 patient who had grade 1 nausea and managed conservatively by antiemetic drug. The results of our study demonstrated expected and favorable biodistribution and dosimetry with 177 Lu-DOTA-trastuzumab in HER2-positive breast carcinoma patients. We noticed the mean absorbed dose to the normal organs within the limits of maximum tolerable dose, and also tumor dose was higher than the normal liver dose. Therefore, we conclude that 177 Lu-DOTA-trastuzumab radioimmunotherapy is feasible and a safe treatment option for treating HER2-positive breast carcinoma patients.

Bone scintigraphy with SPECT/CT in paediatric patients with neck and back pain in comparison with other imaging modalities: the experience of a tertiary paediatric referral centre.

Retrospective review of the additional clinical value provided by single photon emission computed tomography-computed tomography (SPECT/CT) in children and adolescents with back pain. A total of 207 consecutive paediatric patients (94 males, 113 females, age range 5-17 years, median age 14 years) were reviewed after referral to the spinal surgery clinic of a paediatric teaching hospital between November 2009 and February 2021. All patients had either only whole spine X-rays or whole spine x-rays and MRI, along with bone scan with planar whole-body images and SPECT/CT (with spot views of painful area). X-ray identified the pain generator in 23 of 177 (13.0%) cases. MRI identified the pain generator in 49 of 165 (29.7%) cases. SPECT/CT reported relevant positive findings which identified the pain generator in 107 of 185 (57.8%) cases. SPECT/CT changed patients' management in 72 of 185 (38.9%) cases. SPECT/CT was most effective at identifying the pain generator in cases of facet arthropathy, previous vertebral fracture and patients with previous deformity correction, where the pain generator was identified in 76.5% (13 of 17), 71.4% (5 of 7) and 63.4% (26 of 41) of cases, respectively. CT settings were adjusted to minimise the radiation burden (50 mAs/80kVp under 8 years, 24 mAs/110 kVp over 8 years). The role of SPECT/CT in diagnosing back pain is justified in selected paediatric patients, particularly with diagnostic uncertainty using conventional imaging. The CT component of the SPECT/CT study produced a lower radiation dose than conventional CT imaging, whilst producing bone images of diagnostic quality.

Improvement of Whole-body Bone Planar Images on a Bone-dedicated Single-photon Emission Computed Tomography Scanner by Blind Deconvolution Algorithm.

We have developed a bone-dedicated collimator with higher sensitivity but slightly degraded resolution on single-photon emission computed tomography (SPECT) for planar bone scintigraphy, compared with conventional low-energy high-resolution collimator. In this work, we investigated the feasibility of using the blind deconvolution algorithm to improve the resolution of planar images on bone scintigraphy. Monte Carlo simulation was performed with the NCAT phantom for modeling bone scintigraphy on the clinical dual-head SPECT scanner (Imagine NET 632, Beijing Novel Medical Equipment Ltd.) equipped with the bone-dedicated collimator. Maximum likelihood estimation method was used for the blind deconvolution algorithm. The initial estimation of point spread function (PSF) and iteration number for the method were determined by comparing the deblurred images obtained from different input parameters. We simulated different tumors in five different locations and with five different diameters to evaluate the robustness of the initial inputs. Furthermore, we performed chest phantom studies on the clinical SPECT scanner. The quantified increased contrast ratio (CR) between the tumor and the background was evaluated. The 2 mm PSF kernel and 10 iterations provided a practical and robust deblurred image on our system. Those two inputs can generate robust deblurred images in terms of the tumor location and size with an average increased CR of 21.6%. The phantom studies also demonstrated the ability of blind deconvolution, using those two inputs, with increased CRs of 17%, 17%, 22%, 20%, and 13% for lesions with diameters of 1 cm, 2 cm, 3 cm, 4 cm, and 5 cm, respectively. It is feasible to use the blind deconvolution algorithm to deblur the planar images for SPECT bone scintigraphy. The appropriate values of the PSF kernel and the iteration number for the blind deconvolution can be determined using simulation studies.

Correlation of 99mTc-DPD bone scintigraphy with histological amyloid load in patients with ATTR cardiac amyloidosis

Abstract Background The significance of measuring 99mTc-labelled-3,3-diphospono-1,2-propanodicarboxylic acid (99mTc-DPD) in transthyretin (ATTR) cardiac amyloidosis has not been adequately studied. This single-centre observational study evaluated the correlation between 99mTc-DPD scintigraphy and histological amyloid load in endomyocardial biopsy (EMB). Methods Twenty-eight patients with biopsy-proven ATTR amyloidosis and concomitantly available 99mTc-DPD scintigraphy were included. Visual Perugini scoring, and (semi-)quantitative analysis of cardiac 99mTc-DPD uptake by planar whole-body imaging and single photon emission computed tomography (SPECT/CT) using regions of interest (ROI) were performed. From this, heart-to-whole-body ratio (H/WB) and heart-to-contralateral-chest ratio (H/CL) were calculated. Histological amyloid load was quantified using two different staining methods. Results Increased cardiac tracer uptake was documented in all patients (planar: ROImean 129 ± 37 cps; SPECT/CT: ROImean 369 ± 142 cps). Histological amyloid load (19 ± 13 %) significantly correlated with Perugini score (r=0.69, p<0.001, Figure 1) as well as with cardiac 99mTc-DPD uptake (planar: r=0.64, p<0.001, Figure 2; H/WB: r=0.50, p=0.014; SPECT/CT: r=0.53, p=0.008; H/CL: r=0.43, p=0.037) (results are shown for correlations with Congo Red-staining). Conclusion In ATTR, cardiac 99mTc-DPD uptake significantly correlated with histological amyloid load in EMB. Further studies are needed to implement thresholds in cardiac 99mTc-DPD uptake measurements for risk stratification and guidance of therapy.

An Intrapatient Dosimetry Comparison of 177Lu-rhPSMA-10.1 and 177Lu-PSMA-I&T in Patients with Metastatic Castration-Resistant Prostate Cancer.

As the use of radioligand therapy moves earlier in the prostate cancer timeline, minimizing the absorbed dose to normal organs while maintaining high tumor radiation doses becomes more clinically important because of the longer life expectancy of patients. We performed an intrapatient comparison of pretherapeutic dosimetry with the novel radiohybrid prostate-specific membrane antigen-targeting radiopharmaceutical 177Lu-rhPSMA-10.1, along with 177Lu-PSMA-I&T, in patients with metastatic castration-resistant prostate cancer. Methods: Four consecutive patients with advanced histologically proven metastatic castration-resistant prostate cancer who were scheduled for radioligand therapy were evaluated. Before undergoing therapy, each patient received 1.06 ± 0.05 GBq of 177Lu-rhPSMA-10.1 and 1.09 ± 0.02 GBq of 177Lu-PSMA-I&T at least 7 d apart. For dosimetric assessment, whole-body planar scintigraphy was performed after 5 min, 4 h, 1 d, 2 d, and 7 d. In addition, SPECT/CT images were acquired over the thorax and the abdomen, 4 h, 1 d, 2 d, and 7 d after injection. Dosimetry of the whole body and salivary glands was based on the evaluation of the counts in whole-body planar imaging. Dosimetry of the kidneys, liver, spleen, bone marrow, and tumor lesions (≤4 per patient) was based on the activity in volumes drawn on SPECT/CT images. Doses were calculated using OLINDA/EXM version 1.0. The therapeutic index (TI), or ratio between mean dose of the metastases and mean dose of the kidneys, was calculated for each patient. Results: We found the dose to the kidneys to be higher with 177Lu-rhPSMA-10.1 than with 177Lu-PSMA-I&T (0.68 ± 0.30 vs. 0.46 ± 0.10 mGy/MBq); however, 177Lu-rhPSMA-10.1 delivered an average of a 3.3 times (range, 1.2-8.3 times) higher absorbed radiation dose to individual tumor lesions. Consequently, intraindividual comparison revealed a 1.1-3.1 times higher TI for 177Lu-rhPSMA-10.1 than for 177Lu-PSMA-I&T in all evaluated patients. The effective whole-body dose was 0.038 ± 0.008 mSv/MBq for 177Lu-rhPSMA-10.1 and 0.022 ± 0.005 mSv/MBq for 177Lu-PSMA-I&T. Conclusion: Using 177Lu-rhPSMA-10.1 can significantly increase the tumor-absorbed dose and improve the TI compared with 177Lu-PSMA-I&T. An improved TI gives the flexibility to maximize tumor-absorbed doses up to a predefined renal dose limit or, in earlier disease, to reduce the radiation exposure to the kidney while still achieving an effective tumor dose. The function of at-risk organs such as the kidneys is being assessed in a prospective clinical trial.

Dosimetry of a Novel 111Indium-Labeled Anti-P-Cadherin Monoclonal Antibody (FF-21101) in Non-Human Primates.

P-cadherin is associated with a wide range of tumor types, making it an attractive therapeutic target. FF-21101 is a human-mouse chimeric monoclonal antibody (mAb) directed against human P-cadherin, which has been radioconjugated with indium-111 (111In) utilizing a DOTA chelator. We investigated the biodistribution of FF-21101(111In) in cynomolgus macaques and extrapolated the results to estimate internal radiation doses of 111In- and yttrium-90 (90Y)-FF-21101 for targeted radioimmunotherapy in humans. Whole-body planar and SPECT imaging were performed at 0, 2, 24, 48, 72, 96, and 120 h post-injection, using a dual-head gamma camera. Volumes of interest of identifiable source organs of radioactivity were defined on aligned reference CT and serial SPECT images. Organs with the highest estimated dose values (mSv/MBq) for FF-21101(111In) were the lungs (0.840), spleen (0.816), liver (0.751), kidneys (0.629), and heart wall (0.451); and for FF-21101(90Y) dose values were: lungs (10.49), spleen (8.21), kidneys (5.92), liver (5.46), and heart wall (2.61). FF-21101(111In) exhibits favorable biodistribution in cynomolgus macaques and estimated human dosimetric characteristics. Data obtained in this study were used to support the filing of an investigational new drug application with the FDA for a Phase I clinical trial.

Correlation of 99mTc-DPD bone scintigraphy with histological amyloid load in patients with ATTR cardiac amyloidosis

Background The significance of measuring 99mTc-labelled-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) in transthyretin (ATTR) cardiac amyloidosis has not been adequately studied. This single-centre observational study evaluated the correlation between 99mTc-DPD scintigraphy and histological amyloid load in endomyocardial biopsy (EMB). Methods Twenty-eight patients with biopsy-proven ATTR amyloidosis and concomitantly available 99mTc-DPD scintigraphy were included. Visual Perugini scoring, and (semi-)quantitative analysis of cardiac 99mTc-DPD uptake by planar whole-body imaging and single photon emission computed tomography (SPECT/CT) using regions of interest (ROI) were performed. From this, heart-to-whole-body ratio (H/WB) and heart-to-contralateral-chest ratio (H/CL) were calculated. The histological amyloid load was quantified using two different staining methods. Results Increased cardiac tracer uptake was documented in all patients (planar: ROImean 129 ± 37 cps; SPECT/CT: ROImean 369 ± 142 cps). Histological amyloid load (19 ± 13%) significantly correlated with Perugini score (r = 0.69, p < .001) as well as with cardiac 99mTc-DPD uptake (planar: r = 0.64, p < .001; H/WB: r = 0.50, p = .014; SPECT/CT: r = 0.53, p = .008; H/CL: r = 0.43, p = .037) (results are shown for correlations with Congo Red-staining). Conclusion In ATTR, cardiac 99mTc-DPD uptake significantly correlated with histological amyloid load in EMB. Further studies are needed to implement thresholds in cardiac 99mTc-DPD uptake measurements for risk stratification and guidance of therapy.

Cardiac DPD-uptake time dependency in ATTR patients verified by quantitative SPECT/CT and semiquantitative planar parameters

BackgroundBone scintigraphy plays an important role in the diagnosis of cardiac Transthyretin-Related Amyloidosis (ATTR). The mechanism of myocardial tracer accumulation and its dependence over time are not fully understood. Recently, a scintigraphic quantification of the cardiac amyloid deposition has been discussed. Nevertheless, little is known regarding the right time of quantitative imaging. MethodsThe geometrical mean of decay corrected total counts over the heart and the heart/whole-body ratio (H/WB) were evaluated in 23 patients undergoing DPD-bone scan with planar whole-body images 1 and 3 hours post injection (p.i.). Myocardial standard uptake values (SUV)peak were assessed in another 15 patients with quantitative SPECT/CT imaging 1 hours and 3 hours p.i.. ResultsTotal counts over the heart (1 hours p.i.: 81,676 cts, range 69,887 to 93,091 cts and 3 hours p.i.: 64,819 cts, range 52,048 to 86,123 cts, P = .0005) and H/WB ratio (1 hours p.i.:0.076 ± 0.020 and 3 hours p.i. 0.070 ± 0.022; P = .0003) were significantly increased 1 hours p.i.. Furthermore median myocardial SUVpeak (1 hours p.i.:12.2, range 9.6 to 18.9 and 3 hours p.i.: 9.6, range 8.2 to 15.0, P = 0.0012) was also significantly higher after 1 hours p.i. compared to 3 hours p.i.. ConclusionCardiac DPD activity and myocardial SUVpeak are time-dependent, which should be considered when using quantitative bone scintigraphy in ATTR patients.

The efficacy of 99mTc-HYNIC-PSMA SPECT/CT in detecting primary lesions and metastasis in newly diagnosed prostate cancer.

Compared with PET/CT or PET/MRI, SPECT/CT is cheaper and more readily accessible. This study was designed to investigate the efficacy of 99mTc-HYNIC-PSMA SPECT/CT in detecting primary tumors and metastases in patients with newly diagnosed prostate cancer (PCa). A retrospective analysis of 31 patients with pathologically proven PCa was performed at Shanghai General Hospital from November 2020 to November 2021. Planar whole-body imaging was performed on all patients with a SPECT/CT scan of PSMA-positive regions 3-4 h after intravenous injection of 740 MBq 99mTc-HYNIC-PSMA. Positive PSMA uptake lesions were evaluated, and SUVmean and SUVmax were measured in each lesion. Associations between SPECT/CT parameters and clinicopathologic factors (tPSA and Gleason Score) were analyzed. The diagnostic capability of SPECT/CT parameters, tPSA, and GS in distant metastatic detection was evaluated by logistic regression. The SUVmean and SUVmax of the high-risk stratification subgroups (tPSA>20 ng/ml, GS ≥8, and tPSA >20 ng/ml and GS≥8) were higher than those of the low-moderate risk stratification subgroups, with sensitivities of 92% and 92%, respectively. Neither SPECT/CT parameters (SUVmean, SUVmax) nor clinicopathologic factors (tPSA, GS) had high sensitivity (80%, 90%, 80%, and 90%, respectively, P <0.05) in distant metastatic prediction. For both the guideline tPSA level (20 ng/ml) and the cut-off level (84.3 ng/ml), the difference in the distant metastasis detection rate between the low predicted tPSA group and the high predicted tPSA group was statistically significant (0% vs. 47.62%, P = 0.005; 9.09% vs. 88.89%, P = 0.000, respectively). Twenty patients with pathological 99mTc-PSMA avid only in the prostate beds underwent radical prostatectomy. Seven of them underwent lymph node dissection, a total of 35 lymph nodes were removed, and no lymph nodes were detected with metastasis, which was consistent with 99mTc-HYNIC-PSMA SPECT/CT. 99mTc-HYNIC-PSMA SPECT/CT is effective in the risk stratification and distant metastasis detection of primary PCa patients. It is of great value in guiding treatment strategies.

First-in-human clinical trial design of a first-in-class theranostic approach with a peptide-based radioligand targeting CA IX-expressing tumors.

TPS3160 Background: Expression of carbonic anhydrase IX (CA IX), a cell surface glycoprotein, can be induced by a state of hypoxia or by mutation of the Von Hippel-Lindau tumor suppressor gene. CAIX expression in tumors is often associated with progressive disease and overall poor outcomes in various solid cancers. Notably, high CA IX expression has been observed in 83%, 40%, and 29% of clear cell renal cell carcinoma (ccRCC), pancreatic ductal adenocarcinoma (PDAC), and colorectal cancer (CRC) specimens, respectively1. CA IX may therefore represent a valuable therapeutic target. DPI-4452 is a first-in-class cyclic peptide that binds with high affinity to CA IX. Radiolabeling DPI-4452 with gallium-68 ([68Ga]Ga-DPI-4452) or lutetium-177 ([177Lu]Lu-DPI-4452) is an innovative theranostic approach for identifying and treating patients (pts) with CA IX-expressing tumors. Pre-clinical data has shown that [177Lu]Lu-DPI-4452 is taken up by tumors and induces dose-dependent growth inhibition in ccRCC and CRC xenograft mouse models1,2. Methods: We present the design of a Phase I/II study (NCT05706129) of [68Ga]Ga-DPI-4452 and [177Lu]Lu-DPI-4452 in pts with unresectable locally advanced or metastatic ccRCC, CRC or PDAC. The study is comprised of three phases: imaging (Part A), dose-escalation (Part B), and expansion (Part C). In Part A, pts will receive a single intravenous (IV) 185 MBq dose of [68Ga]Ga-DPI-4452. Safety, tolerability, pharmacokinetics (PK), dosimetry and imaging characteristics of [68Ga]Ga-DPI-4452 will be evaluated using positron emission tomography/computed tomography (CT) at four timepoints on Day 1. All pts will be followed for seven days post-injection for safety observations. In Part B, based on [68Ga]Ga-DPI-4452 uptake, pts will receive sequential, escalating doses of IV [177Lu]Lu-DPI-4452 on Day 1 of each 28-day cycle for up to eight cycles. During Cycle 1, each pt will undergo up to four whole-body planar imaging and single photon emission CT/CT analyses for dosimetry over seven days. In Part B, the recommended Phase 2 dose of [177Lu]Lu-DPI-4452 will be determined, guided by a Bayesian Logistic Regression model. Safety, PK, and dosimetry will be assessed to minimize any radiation-induced toxicity and to optimize absorbed radiation dose in the tumor. Upon completion of Part B, Part C will enroll up to three cohorts of pts with CA IX-positive ccRCC, CRC or PDAC to assess preliminary efficacy of [177Lu]Lu-DPI-4452, with a primary endpoint of objective response rate, as measured by RECIST v1.1. References Wiedemann N et al. J Nucl Med 2022;63(Suppl 2):4048. Attinger A et al. Eur J Nucl Med Mol Imaging 2022;49(Suppl 1):S1–S751. Clinical trial information: NCT05706129 .

Evaluation of Safety, Biodistribution, and Dosimetry of a Long-Acting Radiolabeled Somatostatin Analog 177Lu-DOTA-EB-TATE With and Without Amino Acid Infusion.

Kidney is considered to be one of the dose-limiting organs in peptide receptor radionuclide therapy (PRRT). Amino acid cocktail infusion has been applied to reduce renal absorbed dose by inhibiting the proximal tubular reabsorption of the radiopeptide. An Evans blue-modified 177Lu-labeled octreotate (177Lu-DOTA-EB-TATE) has an extended circulation in the blood, which may make the amino acid infusion unnecessary. The aim of this study was to evaluate the safety, biodistribution, and dosimetry of 177Lu-DOTA-EB-TATE with and without amino acid infusion. Ten patients with metastatic neuroendocrine tumors were randomly divided into 2 groups. The effect of amino acid infusion on renal uptake was assessed in a crossover randomized setting. Group A received 177Lu-DOTA-EB-TATE at a dose of 3.7 GBq without amino acid infusion for the first cycle and with amino acid infusion for the second cycle; group B received 177Lu-DOTA-EB-TATE at a dose of 3.7 GBq with amino acid infusion for the first cycle and without amino acid infusion for the second cycle. All patients underwent serial whole-body planar imaging at 1, 24, 96, and 168 hours and SPECT scan at 24 hours after radioligand administration. Abdominal CT was performed 2 days before PRRT for SPECT/CT fusion. The dosimetry was calculated using the HERMES software. Dosimetry evaluation was compared on a between-group and intrapatient basis. Administrations of 177Lu-DOTA-EB-TATE with or without amino acids were well tolerated. No grade 4 hematotoxicity was observed in any of the patients. Grade 3 thrombocytopenia was reported in 1 patient. No nephrotoxicity of any grade was recorded. No significant difference was observed in creatinine (75.1 ± 21.7 vs 67.5 ± 18.1 μmol/L, P = 0.128), blood urea nitrogen (4.5 ± 0.8 vs 5.1 ± 1.4 mmol/L, P = 0.612), or GFR (109.3 ± 25.2 vs 100.9 ± 24.9 mL/min, P = 0.398) before and after PRRT. For each cycle, there was no significant difference in whole-body effective dose, kidney effective dose, as well as residence time of the kidneys between group A and B (P > 0.05). By intrapatient comparison, without and with amino acid infusion also did not show significant difference in whole-body effective dose (0.14 ± 0.05 vs 0.12 ± 0.04 mSv/MBq, P = 0.612), kidney effective dose (1.09 ± 0.42 vs 0.73 ± 0.31 mSv/MBq, P = 0.093), and residence time of the kidneys (2.95 ± 1.58 vs 3.13 ± 1.11 hours, P = 0.674). 177Lu-DOTA-EB-TATE PRRT with and without amino acid infusion demonstrated a favorable safety profile in neuroendocrine tumor patients. Administration of 177Lu-DOTA-EB-TATE without amino acid infusion has acceptable slightly increased kidney absorbed dose and residence time of the kidneys, and does not affect kidney function. Further investigation in a larger cohort and long-term follow-up are warranted.

Radioimmunoscintigraphy and Pretreatment Dosimetry of 131I-Omburtamab for Planning Treatment of Leptomeningeal Disease.

Radiolabeled antibody treatment with 131I-omburtamab, administered intraventricularly into the cerebrospinal fluid (CSF) space, can deliver therapeutic absorbed doses to sites of leptomeningeal disease. Assessment of distribution and radiation dosimetry is a key element in optimizing such treatments. Using a theranostic approach, we performed pretreatment 131I-omburtamab imaging and dosimetric analysis in patients before therapy. Methods: Whole-body planar images were acquired 3 ± 1, 23 ± 2, and 47 ± 2 h after intracranioventricular administration of 75 ± 5 MBq of 131I-omburtamab via an Ommaya reservoir. Multiple blood samples were also obtained for kinetic analysis. Separate regions of interest (ROIs) were manually drawn to include the lateral ventricles, entire spinal canal CSF space, and over the whole body. Count data in the ROIs were corrected for background and physical decay, converted to activity, and subsequently fitted to an exponential clearance function. The radiation absorbed dose was estimated to the CSF, separately to the spinal column and ventricles, and to the whole body and blood. Biodistribution of the injected radiolabeled antibody was assessed for all patients. Results: Ninety-five patients were included in the analysis. Biodistribution showed prompt localization in the ventricles and spinal CSF space with low systemic distribution, noted primarily as hepatic, renal, and bladder activity after the first day. Using ROI analysis, the effective half-lives were 13 ± 11 h (range, 5-75 h) for CSF in the spinal column, 8 ± 3 h (range, 3-17 h) for ventricles, and 41 ± 11 (range, 23-81 h) for the whole body. Mean absorbed doses were 0.63 ± 0.38 cGy/MBq (range, 0.24-2.25 cGy/MBq) for CSF in the spinal column, 1.03 ± 0.69 cGy/MBq (range, 0.27-5.15 cGy/MBq) for the ventricular CSF, and 0.45 ± 0.32 mGy/MBq (range, 0.05-1.43 mGy/MBq) for the whole body. Conclusion: Pretherapeutic imaging with 131I-omburtamab allows assessment of biodistribution and dosimetry before the administration of therapeutic activity. Absorbed doses to the CSF compartments and whole body derived from the widely applicable serial 131I-omburtamab planar images had acceptable agreement with previously reported data determined from serial 124I-omburtamab PET scans.

Dosimetry estimation and preliminary clinical application of [99mTc]Tc-HYNIC-PSMA-XL-2 in prostate cancer.

Molecular imaging of prostate-specific membrane antigen (PSMA) inhibitors has become a favorite for prostate cancer (PCa). This study aimed to estimate the dosimetry and the preliminary clinical application of the [99mTc]Tc-HYNIC-PSMA-XL-2, which is a novel imaging tracer invented by our team that can specifically targets PSMA for PCa and its metastases. The single-photon emission computed tomography (SPECT) whole-body (WB) planar images were collected on 6 patients at 0.5, 1.0, 2.0, 4.0 and 8.0h after 99mTc-PSMA-XL-2 injection, respectively. The SPECT/computed tomography (CT) scan was carried out immediately following the WB planar image scan performed after 2.0h. The volumes of interest (VOIs) of the bladder, heart wall, intestines, kidneys, liver, lungs, and spleen were segmented in the SPECT/CT images. VOIs of the salivary glands and the whole body were drawn in SPECT planar images. The dosimetry toolkit was used to process the data and project the SPECT/CT images onto planar images. The dosimetry analysis was performed using the IDAC-Dose dosimetry software. Furthermore, other PCa patients were enrolled to study the preliminary clinical application of [99mTc]Tc-HYNIC-PSMA-XL-2. The clearance of [99mTc]Tc-HYNIC-PSMA-XL-2 is primarily by the hepatobiliary and intestinal system, due to its lipophilic characteristic. The effective half-life of [99mTc]Tc-HYNIC-PSMA-XL-2 is about 3.90h. High absorbed doses were observed in the salivary glands (1.93E-02 ± 3.88E-03mSv/MBq), kidneys (1.63E-02 ± 7.32E-03mSv/MBq) and spleen (1.21E-02 ± 2.64E-03mSv/MBq). The total body effective dose was 4.84E-03 ± 9.30E-05mSv/MBq. The preliminary clinical case indicated that [99mTc]Tc-HYNIC-PSMA-XL-2 SPECT/CT could detect the primary prostate lesion, lymph node and bone metastases comprehensively. [99mTc]Tc-HYNIC-PSMA-XL-2 is a safe SPECT/CT tracer, which can detect prostate malignant lesions without interference from the bladder. In addition, the malignant lesions of the lymph node and bone of PCa patients also can be detected efficiently.

Histological validation of cardiac 99mTc-DPD uptake in patients with cardiac transthyretin amyloidosis

Abstract Background Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal disease caused by the extracellular deposition of misfolded ATTR protein in the myocardium. In an era where new therapies are rapidly emerging, development of non-invasive imaging modalities to quantify amyloid burden over time is of utmost importance. Although endomyocardial biopsy (EMB) remains the gold standard in amyloid detection and typing, 99mTc-DPD scintigraphy is a widely available and accurate tool for non-invasive diagnosis of cardiac ATTR amyloidosis. However, it remains to be determined whether the degree of cardiac 99mTc-DPD uptake correlates with the histological amyloid infiltration on EMB – thus, justifying 99mTc-DPD scintigraphy as a disease monitoring tool. Aim This single-centre observational study aimed to compare the extent of histologic amyloid burden on EMB with the quantification of cardiac 99mTc-DPD uptake on scintigraphic planar images and SPECT/CT acquisitions in cardiac ATTR amyloidosis. Methods 26 patients with cardiac ATTR amyloidosis were enrolled. Patients were included in case of (1) EMB-proven ATTR amyloidosis and (2) availability of 99mTc-DPD scintigraphy (reference activity: 550 MBq). Visual interpretation using the Perugini score, quantitative analysis of cardiac 99mTc-DPD uptake by planar whole-body imaging and SPECT/CT using regions of interest (ROI) were performed, and heart to whole-body ratio (H/WB) was measured. Histological amyloid load was quantified as percentage of the analysed myocardial tissue using Sulfated Alcyan Blue staining and the Fiji-ImageJ programme. Pearson's and Spearman's correlation were used for correlation analysis and assessment of agreement. Results ATTR patients had a median age of 77 [73–79] years and were predominantly male (85%). An abnormal Perugini score (i.e. 2 or 3) was present in 25 patients (96%), whereas 1 patient was assigned Perugini score 1 (4%). Increased cardiac tracer uptake was documented in all patients, both on 99mTc-DPD planar scintigraphy (ROImean 129±37) and SPECT/CT (ROImean 369±142). Histologic amyloid burden on EMB was 32±19% on average. It significantly correlated with Perugini score (r=0.56 p=0.003), as well as with cardiac 99mTc-DPD uptake (planar: r=0.54 p=0.006, SPECT/CT: r=0.48 p=0.018) and H/WB (r=0.41 p=0.046). Conclusion We have demonstrated a good correlation between histological amyloid infiltration on EMB and cardiac 99mTc-DPD uptake on scintigraphic planar images and SPECT/CT scans, illustrating the potential of 99mTc-DPD scintigraphy to yield reliable quantitative information on cardiac amyloid burden. Further investigations with a larger number of patients are needed to confirm our findings and to implement thresholds in cardiac 99mTc-DPD uptake for being used for guiding disease and therapy management. Funding Acknowledgement Type of funding sources: None.