Gamma Camera Imaging Research Articles

Dosimetry of 131I in remnant ablation and metastasis of differentiated thyroid cancer treated with high radioactivities and rhTSH

Purpose: Ruling out that healthy organs receive doses higher than those allowed in treatments with Iodo-131 (131I) for ablation of thyroid remnant is crucial for the radiological protection of the patient who also received the recombinant human thyroid-stimulating hormone (rhTSH). So, the investigation aimed to determine the changes in energy imparted by 131I in multiple organs due to the rhTSH in thyroid remnants and metastases of patients treated with high 131I activities (≥ 5,550 MBq). Materials and methods: Nine patients were divided into three groups (three per group); Group I included thyroid hormone withdrawal (THW) patients, while patients in groups II and III were stimulated with rhTSH. The activity and absorbed dose in regions of interest (ROIs) was quantified using the conjugated views method using gamma camera images. Results and discussion: Dosimetric variations of 131I produced by using rhTSH in the remnant thyroid (groups II and III) were observed, absorbed doses were minor for groups treated with rhTSH. Conclusion: The application of the high activities > 5,500 MBq administered together with the application of rhTSH is safe in dosimetric terms, also for 9250 MBq do not exceed established limits of absorbed dose in the bone marrow. Furthermore, these high activities provide more than three times the radiation dose to remaining thyroid tissue and approximately 1.5 times to metastases.

Qualitative and quantitative imaging of alpha‐emitting radiopharmaceuticals

AbstractTargeted alpha (α) therapy (TAT) is an emerging therapeutic strategy for cancer treatment. To evaluate the safety and efficacy of targeted α‐therapy, the biodistribution and internal radiation dose of α‐emitting radionuclides should be determined. In vivo imaging of these radionuclides often involves the detection of gamma rays, X‐rays, and positrons generated during their complex decay processes. This review aims to classify the α‐emitting radionuclides (astatine‐211, actinium‐225, radium‐223, bismuth‐212, bismuth‐213, thorium‐227, and terbium‐149) according to their imageable signals. Additionally, this study summarizes various imaging modalities, including gamma camera imaging, single‐photon emission computed tomography, positron emission tomography, Compton imaging, bremsstrahlung imaging, and Cerenkov luminescence imaging, which hold potential for imaging α‐emitting radionuclides, to explore their biomedical applications in qualitative nuclide tracing and diagnosis, quantifying pharmacokinetics, and assessing prognosis and response to therapy.

A Novel Dual-labeled Peptide for Multimodal Imaging of EGFR with L858R Mutation.

The development of molecular imaging agents targeting epidermal growth factor receptor (EGFR) with L858R mutation may help with the selection of non-small cell lung carcinoma (NSCLCL) patients who may benefit from EFGR tyrosine kinase inhibitor (TKI) therapy. In this study, we developed 99mTc STHHYYP-GHEG-ECGK-tetramethylrhodamine (STHHYYP-ECGK-TAMRA) to target EGFR with L858R mutation in NSCLC tumors and verified its probability as a molecular imaging agent. Fmoc solid-phase peptide synthesis was used to synthesize STHHYYP-ECGKTAMRA. 99mTc labelled STHHYYP-ECGK-TAMRA was prepared. Gamma imaging, fluorescent imaging and biodistribution were performed in murine models bearing NCI-H1975 and NCI-H1650 tumors. The binding affinity value (Kd) of 99mTc STHHYYP-ECGK-TAMRA was estimated to be 130.6 ± 29.2 nM in NCI-H1975 cells. The gamma camera images showed a substantial uptake of 99mTc STHHYYP-ECGK-TAMRA in the NCI-H1975 tumor. The % injected dose/gram of the NCI-H1975 tumor tissue was 2.77 ± 0.70 and 3.48 ± 1.01 at 1 and 3 h, respectively. Specific binding of 99mTc STHHYYP-ECGK-TAMRA to L858R-mutated EGFRpositive NCI-H1975 cells and tumors was demonstrated in in vivo and in vitro studies. The results suggest that 99mTc STHHYYP-ECGK-TAMRA is a good candidate agent for dualmodality imaging targeting EGFR with L858R mutation.

Gamma camera imaging characteristics of 166Ho and 99mTc used in Selective Internal Radiation Therapy

BackgroundThe administration of a 166Ho scout dose is available as an alternative to 99mTc particles for pre-treatment imaging in Selective Internal Radiation Therapy (SIRT). It has been reported that the 166Ho scout dose may be more accurate for the prediction of microsphere distribution and the associated therapy planning. The aim of the current study is to compare the scintigraphic imaging characteristics of both isotopes, considering the objectives of the pre-treatment imaging using clinically geared phantoms.MethodsPlanar and SPECT/CT images were obtained using a NEMA image quality phantom in different phantom setups and another body-shaped phantom with several inserts. The influence of collimator type, count statistics, dead time effects, isotope properties and patient obesity on spatial resolution, contrast recovery and the detectability of small activity accumulations was investigated. Furthermore, the effects of the imaging characteristics on personalized dosimetry are discussed.ResultsThe images with 99mTc showed up to 3 mm better spatial resolution, up to two times higher contrast recovery and significantly lower image noise than those with 166Ho. The contrast-to-noise ratio was up to five times higher for 99mTc than for 166Ho. Only when using 99mTc all activity-filled spheres could be distinguished from the activity-filled background. The measurements mimicking an obese patient resulted in a degraded image quality for both isotopes.ConclusionsOur measurements demonstrate better scintigraphic imaging properties for 99mTc compared to 166Ho in terms of spatial resolution, contrast recovery, image noise, and lesion detectability. While the 166Ho scout dose promises better prediction of the microsphere distribution, it is important to consider the inferior imaging characteristics of 166Ho, which may affect individualized treatment planning in SIRT.

NaI gamma camera performance for high energies: Effects of crystal thickness, photomultiplier tube geometry and light guide thickness.

Gamma camera imaging, including single photon emission computed tomography (SPECT), is crucial for research, diagnostics, and radionuclide therapy. Gamma cameras are predominantly based on arrays of photon multipliers tubes (PMTs) that read out NaI(Tl) scintillation crystals. In this way, standard gamma cameras can localize ɣ-rays with energies typically ranging from 30 to 360keV. In the last decade, there has been an increasing interest towards gamma imaging outside this conventional clinical energy range, for example, for theragnostic applications and preclinical multi-isotope positron emission tomography (PET) and PET-SPECT. However, standard gamma cameras are typically equipped with 9.5mm thick NaI(Tl) crystals which can result in limited sensitivity for these higher energies. Here we investigate to what extent thicker scintillators can improve the photopeak sensitivity for higher energy isotopes while attempting to maintain spatial resolution. Using Monte Carlo simulations, we analyzed multiple PMT-based configurations of gamma detectors with monolithic NaI (Tl) crystals of 20 and 40mm thickness. Optimized light guide thickness together with 2-inch round, 3-inch round, 60×60 mm2 square, and 76×76 mm2 square PMTs were tested. For each setup, we assessed photopeak sensitivity, energy resolution, spatial, and depth-of-interaction (DoI) resolution for conventional (140keV) and high (511keV) energy ɣ using a maximum-likelihood algorithm. These metrics were compared to those of a "standard" 9.5mm-thick crystal detector with 3-inch round PMTs. Estimated photopeak sensitivities for 511keV were 27% and 53% for 20 and 40mm thick scintillators, which is respectively, 2.2 and 4.4 times higher than for 9.5mm thickness. In most cases, energy resolution benefits from using square PMTs instead of round ones, regardless of their size. Lateral and DoI spatial resolution are best for smaller PMTs (2-inch round and 60×60 mm2 square) which outperform the more cost-effective larger PMT setups (3-inch round and 76×76 mm2 square), while PMT layout and shape have negligible (<10%) effect on resolution. Best spatial resolution was obtained with 60×60 mm2 PMTs; for 140keV, lateral resolution was 3.5mm irrespective of scintillator thickness, improving to 2.8 and 2.9mm for 511keV with 20 and 40mm thick crystals, respectively. Using the 3-inch round PMTs, lateral resolutions of 4.5 and 3.9mm for 140keV and of 3.5 and 3.7mm for 511keV were obtained with 20 and 40mm thick crystals respectively, indicating a moderate performance degradation compared to the 3.5 and 2.9mm resolution obtained by the standard detector for 140 and 511keV. Additionally, DoI resolution for 511keV was 7.0 and 5.6mm with 20 and 40mm crystals using 60×60 mm2 square PMTs, while with 3-inch round PMTs 12.1 and 5.9mm were obtained. Depending on PMT size and shape, the use of thicker scintillator crystals can substantially improve detector sensitivity at high gamma energies, while spatial resolution is slightly improved or mildly degraded compared to standard crystals.

STUDY OF POISSON NOISE REDUCTION ON GAMMA CAMERA IMAGE USING SPATIAL DOMAIN FILTER

A gamma camera image is produced by a gamma camera that detects the gamma radiation emitted by the radioactive substance or radiopharmaceutical injected into the body. The gamma camera image sometimes has noise that can interfere with the diagnosis. This image is commonly affected by a Poisson-type random noise. This research proposes using a spatial domain filter to study Poisson noise reduction in gamma camera images. The image sample used is the image of a mouse injected with Lu-177-DOTA Trastuzumab with 100 µCi activity detected using a dual-head gamma camera with NaI(Tl) detectors. The grayscale image is treated with Poisson noise, then improved using a spatial domain filter. The spatial domain filters used include Mean, Median, Wiener, and Spatial Lowpass Filters. The mean filter is the best one that can reduce Poisson noise among the four applied filters. The best filter size for noise reduction is 3 with MSE 5.07, PSNR 41.08 dB, and SSIM 0.99.

Abstract B043: Radiolabelled Trastuzumab Fab as a theranostic agent for HER2 expressing breast cancer

Abstract Breast cancer is the most common cause of mortality among women worldwide. Among all subtypes, HER2-positive breast cancers are highly aggressive and have poor prognosis. Surgical resection is choice of treatment. However, surgery may not be possible if disease is widespread. Trastuzumab, a monoclonal antibody, is globally used for immunotherapy. It is a large sized molecule (141kDa) and show slow pharmacokinetics and high liver uptake. We have explored trastuzumab fragment as a radio-theranostic agent. Trastuzumab Fab was generated using Papain enzyme tagged beads, incubation time 18 to 20 h at 850 rpm in phosphate buffer. Fab were collected with ultrafiltration device, cut off 30 kDa, in phosphate buffer pH 8. Quantification of Fab was done at 280 nm. Fab characterization was done using MALDI-TOF and SDS-PAGE. To enable radiolabelling of Fab with Ga-68 and Lu-177, Fab was conjugated with bifunctional chelator, DTPA. Fab-DTPA was separated by micro bio-spin P-6 chromatography columns and the average number of DTPA/Fab were calculated. Affinity of Fab conjugated Fab-DTPA for HER2 receptors was studied using the biolayer interferometry technique (BLI). Radiolabelling of Fab with Ga-68 for PET imaging and Lu-177 for therapy was optimized. Quality control included radiochemical purity using TLC in sodium citrate (pH 5) mobile phase, pyrogenicity using PTS, and sterility by tryptic soy broth culture media. Receptor affinity and apoptosis were studied with HER2 positive SKBR-3 cells using flow cytometry assay. The SKBR-3 cell (106) were cultured in 96 well plates and incubated with a known amount of Lu-177-DTPA-Fab (0- 18.5 MBq). First in human Ga-68 Fab PET/CT and Lu-177-Fab gamma camera images were acquired after obtaining clearance from Institutional Ethics Committee and inform signed consent. Patients were recruited with histopathological proven HER2 positive breast cancer and uptake on F-18 FDG PET/CT. Ga-68-DTPA-Fab (3.5-5 mCi) and 10-15 mCi Lu-177 DTPA-Fab was injected and images were acquired at 2/3 h and up to 7 days respectively. Dominant Fab peak at 45kDa on MALD-TOF, single band on SDS-PAGE (Non-reduced or reduced) have been obtained. Two DTPA/Fab were conjugated and confirmed by MALDI-TOF. BLI data showed Kd value of trastuzumab, Fab, and conjugated DTPA-Fab as 0.2 nM, 0.57 nM, and 20 nM for HER2. High labelling efficiency (≥98%) of Lu-177-DTPA-Fab and Ga-68-DTPA-Fab was achieved. Apoptosis (%) was 1.5%- 42.5% in SKBR-3 cells treated with Lu-177-DTPA-Fab. Both formulations were found sterile and pyrogen-free. Kidney and bladder activity of Ga-68/Lu-177-DTPA-Fab demonstrate renal clearance. Blood pool activity of both tracers were high. However, it was decreased, and lesion uptake was increased with time. All the lesions on Ga-68-DTPA-Fab, same as in F-18 FDG PET/CT, were picked up accept those near heart. Good lesion retention of Lu-177-DTPA-Fab was observed showing suitability for therapy. Fab-DTPA has potential to target HER2 receptor. It could be radiolabelled with Ga-68 for PET imaging and Lu-177 for targeted therapy. Citation Format: Jaya Shukla, Yogesh Rathore, Komalpreet Kaur, Santosh Irrinky, Rajender Kumar, Amanjit Bal, Bhagwant R Mittal. Radiolabelled Trastuzumab Fab as a theranostic agent for HER2 expressing breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B043.

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.

The Theranostic Optimization of PSMA-GCK01 Does Not Compromise the Imaging Characteristics of [99mTc]Tc-PSMA-GCK01 Compared to Dedicated Diagnostic [99mTc]Tc-EDDA/HYNIC-iPSMA in Prostate Cancer

PurposeRadiolabeled PSMA-ligands play a major role in today’s nuclear medicine. Since approval of [177Lu]Lu-PSMA-617 for therapy of metastatic prostate cancer, availability of 177Lu became bottleneck of supply due to the high demand. Recently, a theranostic PSMA-ligand, PSMA-GCK01, was developed which can be labeled either diagnostically with 99mTc or therapeutically with 188Re with both nuclides available from well-known generator systems. This novel tracer might aid to overcome aforementioned supply limitations. In this investigation, the biodistribution and general imaging characteristics of [99mTc]Tc-PSMA-GCK01 were compared with the diagnostic reference compound [99mTc]Tc-EDDA/HYNIC-iPSMA in patients with advanced stage prostate cancer. In addition, the binding of both ligands to PSMA was analyzed at the molecular level using molecular docking.ProceduresTwo cohorts (n = 19 vs. n = 21) of patients with metastatic castration-resistant prostate cancer matched for age, tumor stage, and Gleason score underwent a planar gamma camera imaging with [99mTc]Tc-EDDA/HYNIC-iPSMA or [99mTc]Tc-PSMA-GCK01 prior to PSMA-ligand therapy for PSMA-phenotyping. The imaging data were retrospective analyzed for salivary gland, kidney, liver, soft tissue, and tumor uptake on a semi-automated ROI-analysis using HERMES Medical Solutions AB (HMS, Sweden).ResultsThe data sets were semi-automated quantified on a ROI-based analysis. The tumor-to-background presented equal results of [99mTc]Tc-PSMA-GCK01 compared to [99mTc]Tc-EDDA/HYNIC-iPSMA. The physiological PSMA-positive organs like salivary gland presented also equal uptake in counts/MBq (salivary gland median 9.48 [99mTc]Tc-PSMA-GCK01 vs. median 9.11 [99mTc]Tc-EDDA/HYNIC-iPSMA), while liver-to-kidney ratio presented a slight shift to the liver parenchyma using [99mTc]Tc-PSMA-GCK01 (0.83) compared to [99mTc]Tc-EDDA/HYNIC-iPSMA (0.55) with no statistical significance. This is in agreement with the results from the docking study revealing only a minor difference in the docking scores for both ligands.ConclusionsThe novel theranostic tracer [99mTc]Tc/[188Re]Re-PSMA-GCK01 demonstrates comparable general imaging characteristic with the reference compound [99mTc]Tc-EDDA/HYNIC-iPSMA. These results pave the way for the PSMA-targeting imaging and theranostic agents for a broader, rather low-cost, generator applied radio-ligand therapy utilization.

Estimating blurless and noise-free Ir-192 source images from gamma camera images for high-dose-rate brachytherapy using a deep-learning approach

Objective. Precise monitoring of the position and dwell time of iridium-192 (Ir-192) during high-dose-rate (HDR) brachytherapy is crucial to avoid serious damage to normal tissues. Source imaging using a compact gamma camera is a potential approach for monitoring. However, images from the gamma camera are affected by blurring and statistical noise, which impact the accuracy of source position monitoring. This study aimed to develop a deep-learning approach for estimating ideal source images that reduce the effect of blurring and statistical noise from experimental images captured using a compact gamma camera. Approach. A double pix2pix model was trained using the simulated gamma camera images of an Ir-192 source. The first model was responsible for denoising the Ir-192 images, whereas the second model performed super resolution. Trained models were then applied to the experimental images to estimate the ideal images. Main results. At a distance of 100 mm between the compact gamma camera and the Ir-192 source, the difference in full width at half maximum (FWHM) between the estimated and actual source sizes was approximately 0.5 mm for a measurement time of 1.5 s. This difference has been improved from approximately 2.7 mm without the use of DL. Even with a measurement time of 0.1 s, the ideal images could be estimated as accurately as in the 1.5 s measurements. This method consistently achieved accurate estimations of the source images at any position within the field of view; however, the difference increased with the distance between the Ir-192 source and the compact gamma camera. Significance. The proposed method successfully provided estimated images from the experimental images within errors smaller than 0.5 mm at 100 mm. This method is promising for reducing blurring and statistical noise from the experimental images, enabling precise real-time monitoring of Ir-192 sources during HDR brachytherapy.

Deep Learned Segmentations of Inflammation for Novel ⁹⁹mTc-maraciclatide Imaging of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease that causes joint pain, stiffness, and erosion. Power Doppler ultrasound and MRI are imaging modalities used in detecting and monitoring the disease, but they have limitations. ⁹⁹mTc-maraciclatide gamma camera imaging is a novel technique that can detect joint inflammation at all sites in a single examination and has been shown to correlate with power Doppler ultrasound. In this work, we investigate if machine learning models can be used to automatically segment regions of normal, low, and highly inflamed tissue from 192 ⁹⁹mTc-maraciclatide scans of the hands and wrists from 48 patients. Two models were trained: a thresholding model that learns lower and upper threshold values and a neural-network-based nnU-Net model that uses a convolutional neural network (CNN). The nnU-Net model showed 0.94 ± 0.01, 0.51 ± 0.14, and 0.76 ± 0.16 modified Dice scores for segmenting the normal, low, and highly inflamed tissue, respectively, when compared to clinical segmented labels. This outperforms the thresholding model, which achieved modified Dice scores of 0.92 ± 0.01, 0.14 ± 0.07, and 0.35 ± 0.21, respectively. This is an important first step in developing artificial intelligence (AI) tools to assist clinicians' workflow in the use of this new radiopharmaceutical.

Development of a Radiolabeled Folate-Mediated Drug Delivery System for Effective Delivery of Docetaxel.

Many preclinical studies are carried out with the aim of developing new formulations for the effective delivery of taxane class drugs, one of the most important anticancer drugs used clinically today. In this study, a radiolabeled folate-mediated solid lipid magnetic nanoparticle (SLMNP) system was developed by loading superparamagnetic iron oxide nanoparticles (MNP) and docetaxel (DTX) into the solid lipid nanoparticles as a drug delivery system that will function both in cancer treatment and diagnosis. For this purpose, first, SLMNP was synthesized by the hot homogenization method, and the surface of the particles was modified with a folate derivative to carry the particles to tissues with folate receptors. The synthesized magnetic solid lipid nanoparticles were loaded with DTX, and then radiolabeling was carried out with technetium-99 m (99mTc-DTX-SLMNP). Structural characteristics of these nanoparticles were determined by characterization methods. According to the TEM images of MNPs, SLN, and SLMNPs, MNPs were observed between 25and 35 nm, SLNs between 400 and 500 nm, and SLMNPs between 350 and 450 nm. The drug entrapment efficiency of SLMNPs loaded with DTX was found to be 19%, and the percentage efficiency of radiolabeling was found to be 98.0 ± 2.0%. The biological behavior of this radiolabeled system was investigated in vitro and in vivo. Folate receptor-positive SKOV-3 and folate receptor-negative A549 cancer cell lines were studied. The IC50 values of DTX-SLMNP in SKOV-3 and A549 cells were 50.21 and 172.27 μM at 48 h, respectively. Gamma camera imaging studies of 99mTc-DTX-SLMNP and magnetically applied 99mTc-DTX-SLMNP compounds were performed on tumor-bearing CD-1 nude mice. The uptake in the folate receptor-positive tumor region was higher than that in the folate receptor negative tumor region. We proposed that the drug delivery system we prepared in this study be evaluated for preclinical studies of new drug carrier formulations of the taxane class of anticancer drugs.

Feasibility and Performance of Free-Hand Single-Photon Computed Tomography/Ultrasonography for Preoperative Parathyroid Adenoma Localization: A Pilot Study.

The aim of this prospective pilot study was to evaluate the feasibility of a new hybrid imaging modality, free-hand single-photon computed tomography/ultrasonography (fhSPECT/US), for preoperative localization of parathyroid adenomas and to compare its performance with conventional ultrasonography and SPECT/CT. Twelve patients diagnosed with primary hyperparathyroidism underwent sequentially US and parathyroid scintigraphy, including SPECT/CT, followed by fhSPECT/US, allowing for real-time fusion between US and freehand-generated gamma-camera images. The fhSPECT/US detection rates were correlated with histopathology, when available, or with the imaging modality showing the most lesions. Based on a per patient analysis, the detection rate was significantly different when comparing SPECT/CT to fhSPECT/US (p = 0.03), and not significantly different when comparing SPECT/CT to US (p = 0.16) and US to fhSPECT/US (p = 0.08). Based on a per-lesion analysis, the detection rate of SPECT/CT was significantly higher than that of US (p = 0.01) and fhSEPCT/US (p = 0.003), and there was no significant difference in detection rate when comparing US to fhSPECT/US (p = 0.08). The main perceived limitations of fhSPECT/US in lesion detection were: (i) lesions localized at a depth ≥4.5 cm; (ii) imperfect image fusion due to tissue compression; (iii) limited spatial manipulation ability of the SPECT mobile camera handheld probe; and (iv) a wide spread of detected activity. In conclusion, clinical use of fhSPECT/US for localization of parathyroid adenomas is feasible, but shows lower sensitivity than conventional modalities and requires technical improvements.

18F-MFBG PET imaging in patients with neuroblastoma: Lesion targeting and comparison with MIBG.

10046 Background: 123I-MIBG gamma camera imaging (MIBG) is routinely used for the imaging of neuroblastoma. Limitations include need for two-day imaging schedule and lack of quantitative uptake measurements. Phase I study showed that 18 F-MFBG (MFBG), a positron-emitting analog of MIBG, is safe and feasible (PMID:28705916). In the follow-up phase II trial (NCT02348749) we evaluated MFBG PET imaging, comparing neuroblastoma lesion between the two modalities. Methods: Patients with known neuroblastoma underwent whole- body PET CT or PET-MR imaging one hour post-injection with 8mCi/1.7m2 of MFBG. All patients had concurrent MIBG scan with planar and SPECT-CT imaging without intervening therapy. MFBG and MIBG images were independently analyzed for lesion targeting; lesion number, site and uptake was noted for each patient and compared. Discordant lesions were further investigated with correlative imaging and/or clinical follow up. MFBG score was generated, similar to the modified Curie score for MIBG, for each patient. Results: 25 patients (median age 8 y) underwent MFBG scans at a median of 2 (range 0-24) days after MIBG scans; in one patient MFBG scan was performed 1 day before MIBG scan. No MFBG-related adverse events were noted. 24 patients had both MIBG and MFBG positive scans while 1 patient had both MIBG and MFBG negative scans. A total of 367 lesions were visualized on MFBG as against 217 on MIBG. There were no MIBG-positive that were negative on MFBG. A median number of 11 (range 0-57) lesions per patient were detected on MFBG scan. Uptake was noted in osteomedullary only, (n=13), soft tissue only (n=1) and both soft tissue and osseous lesions (n=10). MFBG detected a median of 6 (range 1-24) additional lesions in 19 patients. In 16/19 patients where follow up was available, the discordance was related to true positive disease, including at least 116 sites. Respective median curie scores were 3 (range:0-22) and 9 (range:0-24) with MIBG and MFBG respectively. Conclusions: MFBG scan detected disease in all patients with MIBG positive disease. MFBG detected similar or more lesions compared to MIBG in patients with neuroblastoma, with overall increased scores. Further analysis to evaluate impact on patient management is underway. Clinical trial information: NCT02348749 .

Spatial resolution and natural image quality assessment evaluation of gamma camera image using pinhole collimator in lutetium-yttrium oxyorthosilicate scintillation detector

Scintillator materials are widely used in the medical and industrial fields for imaging systems using gamma cameras. In this study, image evaluation is performed by modeling a gamma camera system based on a lutetium-yttrium oxyorthosilicate (LYSO) scintillation detector using a pinhole collimator that can improve the spatial resolution. A LYSO detector-based gamma camera system is modeled using a Monte Carlo simulation tool. The geometric concept of the pinhole collimator is designed using various magnification factors, and the spatial resolution is measured using the acquired source image. To evaluate the resolution, the full width at half maximum (FWHM) and natural image quality assessment (NIQE), a no-reference-based parameter, are used. We confirm that the FWHM and NIQE values decrease simultaneously when the diameter of the pinhole collimator increases. Additionally, we confirm that the spatial resolution improves as the magnification factor increases under the same pinhole diameter condition. Particularly, a 0.57 mm FWHM value is obtained using the modeled gamma camera system with a LYSO scintillation detector. In conclusion, our results demonstrate that a pinhole collimator with a LYSO scintillation detector is a promising gamma camera imaging system.

Imaging of gamma photons from activated gold wire using a high-energy gamma camera after irradiation of neutrons from boron neutron capture therapy (BNCT) system

Gold wire is commonly used for quality assurance (QA) of the neutron beam in a boron neutron capture therapy (BNCT) system. It is set in water and irradiated with the neutron beam, and then 412-keV gamma photons from the activated gold wire are measured by a semiconductor detector. Since this procedure takes time and labor, a more efficient method is desired. To reduce the time and labor to measure the radioactivity of an activated gold wire, we carried out imaging of 412-keV gamma photons from the activated gold wire using a developed high-energy gamma camera. After the gold wire was set in the depth direction in a water-filled phantom and irradiated with neutron beams using the BNCT system, gamma photon imaging was conducted with the developed high-energy gamma camera. On the measured image, a depth profile was set to obtain the neutron distribution, and this was compared with the profile sequentially measured with a semiconductor detector. An image of the 412-keV gamma photons was obtained with an imaging time of 1.5 hours. The estimated depth profile of the neutron beam from the gamma camera image closely matched that measured with a semiconductor detector. Imaging of the gamma photons emitted from the activated gold wire was possible, and it offers an efficient method to measure the thermal neutron distribution of the BNCT system. This method has the potential to reduce the time and labor for QA of a BNCT system.

First experience with 224Radium-labeled microparticles (Radspherin®) after CRS-HIPEC for peritoneal metastasis in colorectal cancer (a phase 1 study).

Peritoneal metastasis (PM) from colorectal cancer carries a dismal prognosis despite extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). With a median time to recurrence of 11-12 months, there is a need for novel therapies. Radspherin® consists of the α-emitting radionuclide radium-224 (224Ra), which has a half-life of 3.6 days and is adsorbed to a suspension of biodegradable calcium carbonate microparticles that are designed to give short-range radiation to the serosal peritoneal surface linings, killing free-floating and/or tumor cell clusters that remain after CRS-HIPEC. A first-in-human phase 1 study (EudraCT 2018-002803-33) was conducted at two specialized CRS-HIPEC centers. Radspherin® was administered intraperitoneally 2 days after CRS-HIPEC. Dose escalation at increasing activity dose levels of 1-2-4-7-MBq, a split-dose repeated injection, and expansion cohorts were used to evaluate the safety and tolerability of Radspherin®. The aim was to explore the recommended dose and biodistribution using gamma-camera imaging. The results from the planned safety interim analysis after the completion of the dose-limiting toxicity (DLT) period of 30 days are presented. Twenty-three patients were enrolled: 14 in the dose escalation cohort, three in the repeated cohort, and six in the expansion cohort. Of the 23 enrolled patients, seven were men and 16 were women with a median age of 64 years (28-78). Twelve patients had synchronous PM stage IV and 11 patients had metachronous PM [primary stage II; (6) and stage III; (5)], with a disease-free interval of 15 months (3-30). The peritoneal cancer index was median 7 (3-19), operation time was 395 min (194-515), and hospital stay was 12 days (7-37). A total of 68 grade 2 adverse events were reported for 17 patients during the first 30 days; most were considered related to CRS and/or HIPEC. Only six of the TEAEs were evaluated as related to Radspherin®. One TEAE, anastomotic leakage, was reported as grade 3. Accordion ≥3 grade events occurred in a total of four of the 23 patients: reoperation due to anastomotic leaks (two) and drained abscesses (two). No DLT was documented at the 7 MBq dose level that was then defined as the recommended dose. The biodistribution of Radspherin® showed a relatively even peritoneal distribution. All dose levels of Radspherin® were well tolerated, and DLT was not reached. No deaths occurred, and no serious adverse events were considered related to Radspherin®.Clinical Trial Registration: Clinicaltrials.gov, NCT03732781.

Radiation safety considerations for the use of radium-224-calciumcarbonate-microparticles in patients with peritoneal metastasis.

Two ongoing phase I studies are investigating the use of radium-224 adsorbed to calcium carbonate micro particles (224Ra-CaCO3-MP) to treat peritoneal metastasis originating from colorectal or ovarian cancer. The aim of this work was to study the level of radiation exposure from the patients to workers at the hospital, carers and members of the public. Six patients from the phase 1 trial in patients with colorectal cancer were included in this study. Two days after cytoreductive surgery, they were injected with 7 MBq of 224Ra-CaCO3-MP. At approximately 3, 24 and 120 h after injection, the patients underwent measurements with an ionization chamber and a scintillator-based iodide detector, and whole body gamma camera imaging. The patient was modelled as a planar source to calculate dose rate as a function of distance. Scenarios varying in duration and distance from the patient were created to estimate the potential effective doses from external exposure. Urine and blood samples were collected at approximately 3, 6, 24, 48 and 120 h after injection of 224Ra-CaCO3-MP, to estimate the activity concentration of 224Ra and 212Pb. The patients' median effective whole-body half-life of 224Ra-CaCO3-MP ranged from 2.6 to 3.5 days, with a mean value of 3.0 days. In the scenarios with exposure at the hospital (first 8 days), sporadic patient contact resulted in a range of 3.9-6.8 μSv per patient, and daily contact resulted in 4.3-31.3 μSv depending on the scenario. After discharge from the hospital, at day 8, the highest effective dose was received by those with close daily contact; 18.7-83.0 μSv. The highest activity concentrations of 224Ra and 212Pb in urine and blood were found within 6 h, with maximum values of 70 Bq/g for 224Ra and 628 Bq/g for 212Pb. The number of patients treated with 224Ra-CaCO3-MP that a single hospital worker - involved in extensive care - can receive per year, before effective doses of 6 mSv from external exposure is exceeded, is in the order of 200-400. Members of the public and family members are expected to receive well below 0.25 mSv, and therefore, no restrictions to reduce external exposure should be required.

Evaluation of Preoperative and Intraoperative Mobile Gamma Camera Imaging in Sentinel Lymph Node Biopsy for Melanoma Independent of Preoperative Lymphoscintigraphy

IntroductionSentinel lymph node biopsy (SLNB) is a standard practice for staging cutaneous melanoma. High false-negative rates have an increased interest in adjunctive techniques for localizing SLNs. Mobile gamma cameras (MGCs) represent potential tools to enhance SLNB performance. MethodsAn institutional review board approval was obtained for this study (ClinicalTrials.gov ID NCT01531608). After obtaining informed consent, 20 eligible melanoma patients underwent 99mTc sulfur colloid injection and standard lymphoscintigraphy with a fixed gamma camera (FGC). A survey using a 20 cm square MGC, performed immediately preoperatively by the study surgeon, was used to establish an operative plan while blinded to the FGC results. Subsequently, SLNB was performed using a gamma probe and a novel 6 cm diameter handheld MGC. ResultsA total of 24 SLN basins were detected by FGC. Prior to unblinding, all 24 basins were identified with the preoperative MGC and the operative plan established by preoperative MGC imaging was confirmed accurate by review of the FGC images. All individual sentinel lymph nodes were identified during intraoperative MGC imaging, and in 5/24 (21%) cases, surgeon-reported additional clinically useful information was obtained from the MGC. ConclusionsPreoperative MGC images provide information consistent with FGC images for planning SLNB and in some cases provide additional information that aided in surgical decision-making.

Comparison of Aerosol Deposition Between a Cynomolgus Macaque and a 3D Printed Cast Model of the Animal.

Preclinical aerosol studies using animals are essential for evaluating toxic or therapeutic effects on human respiratory tract. Macaques are relevant animal models for respiratory studies, but they are sensitive, expensive and difficult-to-access. In the context of preliminary studies before animal experiments, we set up an alternative in vitro anatomical model of macaque airways to reduce, refine and replace (3Rs) the animals. We printed an in vitro anatomical cast until the third bronchial division from X-ray computed tomography data of a healthy cynomolgus macaque. This in vitro model was then connected to a respiratory pump to mimic macaque's breathing. We assessed the relevance of this in vitro model, by comparing aerosol deposition patterns obtained with the anatomical model and in three macaques using planar gamma camera imaging. DTPA-99mTechnetium aerosols were produced using three jet nebulizers, generating three different particle sizes: 13.1, 3.2 and 0.93µm in terms of the mass median aerodynamic diameter (MMAD). The data showed no statistical differences between the animal and anatomical in vitro models in terms of total aerosol deposited in the airways. However, the distribution of the deposition in the airways showed a higher deposited fraction in the upper respiratory tract in the animals than the in vitro model for all particle sizes. The anatomical printed model appears to be a relevant in vitro tool to predict total aerosol deposition in macaque airways.