An international phantom study of inter-site variability in Technetium-99m image quantification: analyses from the TARGET radioembolization study.

BACKGROUND: Personalised multi-compartment dosimetry based on [99mTc]Tc-MAA is a valuable tool for planning 90Y radioembolization treatments. The establishment and effective application of dose-effect relationships in yttrium-90 (90Y) radioembolization requires [99mTc]Tc-MAA SPECT quantification ideally independent of clinical site. The purpose of this multi-centre phantom study was to evaluate inter-site variability of [99mTc]Tc-MAA imaging and evaluate a standardised imaging protocol. Data was obtained from the TARGET study, an international, retrospective multi-centre study including 14 sites across 8 countries. The impact of imaging related factors was estimated using a NEMA IQ phantom (representing the liver), and a uniformly filled cylindrical phantom (representing the lungs). Imaging was performed using site-specific protocols and a standardized protocol. In addition, the impact of implementing key image corrections (scatter and attenuation correction) in the site-specific protocols was investigated. Inter-site dosimetry accuracy was evaluated by comparing computed Lung Shunt Fraction (LSF) measured using planar imaging of the cylindrical and NEMA phantom, and contrast recovery coefficient (CRC) measured using SPECT imaging of the NEMA IQ phantom. RESULTS: Regarding the LSF, inter-site variation with planar site-specific protocols was minimal, as determined by comparing computed LSF between sites (interquartile range 9.6-10.1%). A standardised protocol did not improve variation (interquartile range 8.4-9.0%) but did improve mean accuracy compared to the site-specific protocols (5.0% error for standardised protocol vs 8.8% error for site-specific protocols). Regarding the CRC, inter-system variation was notable for site-specific SPECT protocols and could not be improved by the standardised protocol (CRC interquartile range for 37 mm sphere 0.5-0.7 and 0.6-0.8 respectively), however the standardised protocol did improve accuracy of sphere:background determination. Implementation of key image corrections did improve inter-site variation (CRC interquartile range for 37 mm sphere 0.6-0.7). CONCLUSION: Eliminating sources of variability in image corrections between imaging protocols reduces inter-site variation in quantification. A standardised protocol was not able to improve consistency of LSF or CRC but was able to improve accuracy.

Influence of Early Versus Delayed Hepatic Artery Perfusion Scan on 90Y Selective Internal Radiation Therapy Planning.

Purpose: This study evaluated the effect of an increase in the time interval between hepatic intra-arterial injection of 99mTc-macroaggregated albumin (MAA) and hepatic artery perfusion scintigraphy (HAPS) on the lung shunt fraction (LSF) and perfused volume (PV) calculations in the treatment planning of selective internal radiation therapy (SIRT). Methods: The authors enrolled 51 HAPS sessions from 40 patients diagnosed with primary or metastatic liver malignancy. All patients underwent scan at the first and fourth hour after hepatic arterial injection of 99mTc-MAA. Based on single-photon emission computed tomography images, LSF values were measured from each patient's first and fourth hour images. PV1 and PV4 were also calculated based on three-dimensional images using 5% and 10% cutoff threshold values and compared with each other. Results: The authors found that the median of LSF4 was statistically significantly higher than LSF1 (3.05 vs. 4.14, p ≤ 0.01). There was no statistically significant difference between PV1 and PV4 on the 10% (p = 0.72) thresholds. Conclusions: LSF values can be overestimated in case of delayed HAPS, potentially leading to treatment cancellation due to incorrectly high results in patients who could benefit from SIRT. Threshold-based PV values do not significantly change over time; nevertheless, keeping the short interval time would be safer.

The inferior performance of [68Ga]Ga-FAPI-04 PET/CT as a diagnostic and theranostic biomarker in [177Lu]Lu-DOTATATE refractory well-differentiated neuroendocrine tumors.

PURPOSE: We aimed to investigate the potential of [68Ga]Ga-FAPI-04 PET/CT as an alternative diagnostic and theranostic tool in well-differentiated NETs refractory to [177Lu]Lu-DOTATATE therapy. METHODS: Patients who received at least two cycles of [177Lu]Lu-DOTATATE therapy for metastatic NETs and progressed under treatment were included. All patients had performed [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI-04 PET/CT within 3 weeks. The number of PET-positive lesions related to NETs and tumor sites was documented. Mann-Whitney U and chi-square tests were used to compare SUVmax levels of tracers and the number of detected metastases. RESULTS: Twelve patients (7 male, 5 female) who met the eligibility criteria were included in the study. Ten patients had grade 1-2 NET of various origins, and two had paraganglioma and pheochromocytoma. One hundred ninety-eight of 230 lesions (86%) were SSTR positive with a median SUVmax of 16.6 (2.2-76.5), and 88 of 230 lesions (38.2%) were [68Ga]Ga-FAPI-04 positive with a median SUVmax of 5.1 (2.3-21). Median SUVmax level and detected number of tumors were significantly higher in [68Ga]Ga-DOTATATE PET/CT (p=<0.001). [68Ga]Ga-FAPI-04 PET/CT was completely (n:2) or almost completely (n:3) negative in 5 (42%) patients. Two (17%) patients had flip-flop SSTR/FAPI uptake in tumors. In four patients (33%), tumor uptake or the number of PET-positive lesions was inferior in [68Ga]Ga-FAPI-04 PET/CT. In only one patient (8%), tumor uptakes were higher in [68Ga]Ga-FAPI-04 PET/CT. Low-dose [177Lu]Lu-FAPI-46 dosimetry was performed on the FAPI-dominant patient; absorbed radiation doses per GBq were 1.26 Gy, 0.36 Gy, 0.32 Gy, and 0.2 Gy for kidneys, liver, spleen, and total body, respectively. The mean absorbed dose per GBq was 0.33 Gy for liver mass and 0.41 Gy for metastatic lymph nodes. CONCLUSION: Our preliminary results demonstrated that [68Ga]Ga-FAPI-04 PET/CT mainly failed in well-differentiated NETs refractory to [177Lu]Lu-DOTATATE therapy and had a limited role as an alternative diagnostic or theranostic agent. Further investigations with a larger patient population are required to determine the impact of [68Ga]Ga-FAPI-04 PET/CT on NETs.

The effects of kilovoltage (kV) and milliampere seconds (mAs) values for SPECT attenuation correction: An anthropomorphic phantom study.

The purpose of SPECT/CT imaging to be used in dosimetric calculations is to perform accurate attenuation correction by giving the patient the minimum radiation dose. in accordance with ALARA principles (as low as reasonably achievable), it is critical to limit the amount of radiation given to the patient as far as possible in medical fields where radiation therapy is applied. The goal of this study is to determine the optimum kV and mAs values needed to keep the radiation dose that can be given to the patient in CT scans at a minimum level for attenuation correction, as well as to determine the CT-induced radiation doses on patients with different kV and mAs values using an anthropomorphic phantom. Radionuclides 177Lu and 131I were used in SPECT imaging. For CT-based attenuation correction, images were taken with various values between 80 kV × 30 mAs and 140 kV × 300 mAs using the anthropomorphic phantom. After that attenuation correction was performed with the obtained CT images for SPECT images. Then, CT-derived radiation doses were calculated. Our results showed that 80 kV × 30 mAs values can be used in scans after radionuclide treatment for CT attenuation correction. It was determined that the patient was exposed to a radiation dose of 0.432 mSv as a result of the CT scanning with the full detector width area of gamma camera detector. Thus, scanning with these values (80 kV × 30 mAs) resulted in approximately 95% less radiation exposure (0,432 mSv) than the value (9,38 mSv) with scanning of the manufacturer's recommended value (120 kV × 200 mAs).

A multi-institutional assessment of eye lens dose in nuclear medicine clinics.

AIM: The endeavor was to measure the lens dose of actively working staff in nuclear medicine departments. MATERIAL AND METHODS: This study was accomplished in three nuclear medicine sites. A total of 23 workers in nuclear medicine joined this work. Among them are 6 SPECT/ CT technologists, 6 PET/CT technologists, 3 PET/MRI technologists, 5 radiopharmacists, 2 physicists, and 1 physician. EXTDOSE Hp(3) OSL dosimeter with tissue equivalent beryllium-oxide crystal was used for lens dose measurement. All participants were asked to wear the lens dosimeter for 2 months as near to the eye level as possible. RESULTS: Pooling the dose measures together yielded an average lens dose of 1.48 ±â€…0.77 mSv for the radiopharmacy team, 1.44 ±â€…0.26 for PET/ CT technologists, 0.86 ±â€…0.45 mSv for SPECT/ CT technologists, 0.38 mSv for the sole physician administered 177Lu, and 0.45 ±â€…0.02 mSv for the physicists conducting 131I therapy. Moreover, normalizing the lens dose to the labeled activity led to a lens dose of 2.2 ±â€…1.4 µSv/GBq for the radiopharmacy team. Likewise, per administered activity: 23.8 ±â€…7.3 µSv/GBq for PET/CT and PET/MRI technologists, 12.2 ±â€…10.5 µSv/GBq 99mTc for SPECT/CT technologists, 6.0 ±â€…0.81 µSv/GBq 131I for physicists, and 3.0 µSv/GBq 177Lu for the physician. CONCLUSION: It was deduced that the annual occupational lens dose of the nuclear medicine workers varied from 2.3 to 11.5 mSv/year; however, one radiopharmacist projected annual lens dose as close to the lens equivalent dose limit (20 mSv/year) as 17.9 mSv.

An anthropomorphic body phantom for the determination of calibration factor in radionuclide treatment dosimetry.

The aim of this study is to create an inhomogeneous human-like phantom, whose attenuation and scattering effects are similar to the human body, as an alternative to the homogeneous phantoms traditionally used in calibration factor (CF) determination. The phantom was designed to include the thorax, abdomen and upper pelvis regions sized to represent a 75-kg male with a body mass index of 25. Measurements using Lu-177 with 50- and 100-mL lesion volumes were performed using inhomogeneous anthropomorphic body phantom (ABP) and homogeneous NEMA PET body phantom. There was a difference of 5.7% of Calibration Factor including attenuation and scatter effect between ABP and NEMA PET body phantom. Because it better reflects the attenuation and scatter effect, it is recommended to use a human-like inhomogeneous phantom for determination of CF instead of a homogeneous phantom.

An Analysis for Therapeutic Doses of Patients with Neuroendocrine Tumor Treated with Lutetium 177 (177Lu)-DOTATATE.

Background: The aim of this study is to clarify the critical organs that limit treatment scheme and also evaluate the validity of currently used critical organ threshold values in neuroendocrine tumor (NET) patients, receiving peptide receptor radionuclide therapy (PRRT) with Lutetium 177 (177Lu)-DOTATATE. Materials and Methods: Thirty-six NET patients (ages 16-73 years) who received 177Lu-DOTATATE treatment were evaluated retrospectively in this study. Dosimetric calculations were made using medical internal radionuclide dose method. For calculation of organ doses, Internal Dose Assessment at Organ Level/Exponential Modelling 1.1 software program was used. Follow-up data were used to determine the organ failure. Results: A total of 141 cycles and mean of 3.91 (±1.33) cycles were applied to the patients. A mean of 691 mCi (±257 mCi) 177Lu-DOTATATE infusion in total and a dose between 70 and 200 mCi per treatment was applied to patients. Seven of 36 patients reached 23 Gy renal dose limit. In these patients, although kidney doses were between 23 and 29 Gy, there was no diminution in renal functions during follow-up. Two of 36 patients reached total bone marrow dose of 2 Gy limit. Bone marrow suppression did not develop in these patients. Conclusion: The critical organs that seem to affect the treatment scheme in PRRT with 177Lu-DOTATATE are kidney and bone marrow. Although there are established threshold levels, derived from radiotherapy experience, more studies are needed to clarify these dose limits in systemic radionuclide therapies such as PRRT.

Safety of Fibroblast Activation Protein-Targeted Radionuclide Therapy by a Low-Dose Dosimetric Approach Using 177Lu-FAPI04.

OBJECTIVES: This study is set out to estimate the radiation-absorbed doses to normal organs and tumor tissue using low-dose 177Lu-FAPI04 dosimetry to determine the safety and theranostic potential of fibroblast activation protein-targeted radionuclide therapy. PATIENTS AND METHODS: Four patients with metastatic advanced-stage cancer were administered low-dose 177Lu-FAPI04 for dosimetry measurements. Data acquisition for dosimetry of normal organs and tumors was performed by whole-body and 3D SPECT/CT imaging at 4, 24, 48, and 96 hours after administering 177Lu-FAPI04. Blood samples were drawn at 5, 15, 30, 60, 60, 120, and 180 minutes, and at 24, 48, and 96 hours for bone marrow dosimetry calculations. RESULTS: Mean absorbed doses per megabecquerel were 0.25 ± 0.16 mGy (range, 0.11-0.47 mGy), 0.11 ± 0.08 mGy (range, 0.06-0.22 mGy), and 0.04 ± 0.002 mGy (range, 0.04-0.046 mGy) for kidneys, liver, and bone marrow, respectively. The respective maximum estimated amount of radioactivity to reach radiation-absorbed dose limits were 120.9 ± 68.6 GBq, 47.5 ± 2.8 GBq, 397.8 ± 217.1 GBq, and 52.4 ± 15.3 GBq for kidneys, bone marrow, liver, and total body. The mean absorbed dose per megabecquerel was 0.62 ± 0.55 mGy for bone metastases, 0.38 ± 0.22 mGy for metastatic lymph nodes, 0.33 ± 0.21 mGy for liver metastases, and 0.37 ± 0.29 for metastatic soft tissue. The maximum absorbed dose in a tumor lesion was 1.67 mGy/MBq for bone, 0.6 mGy/MBq for lymph node, 0.62 mGy/MBq for liver, and 1 mGy/MBq for soft tissue. CONCLUSIONS: The mean absorbed dose to organs at risk with 177Lu-FAPI04 is reasonably low, allowing for low tumor-absorbed dose rates by administering a higher dose. Further research on optimizing therapeutic efficacy and using alternative radioisotopes is necessary, along with an individualized dosimetric approach.

Y90 selective internal radiation therapy and peptide receptor radionuclide therapy for the treatment of metastatic neuroendocrine tumors: combination or not?

BACKGROUND: Peptide receptor radionuclide therapy and selective internal radiation therapy are effective radionuclide therapy modalities for unresectable metastatic neuroendocrine tumor patients that cannot be controlled with somatostatin analogs. The present study is intended to evaluate the therapeutic efficacy and toxicity of the combined therapy of selective internal radiation therapy and peptide receptor radionuclide therapy and stand-alone selective internal radiation therapy in patients with neuroendocrine tumor, a liver-dominant disease. METHODS: This cohort consists of 27 patients with metastatic neuroendocrine tumor and liver-dominant disease. They were grouped as the patients who were treated with selective internal radiation therapy for unresectable liver metastasis (n = 15) and the patients who received a combination of selective internal radiation therapy and peptide receptor radionuclide therapy (n = 12) for hepatic and extrahepatic metastasis. Treatment efficacy and treatment-associated toxicity were retrospectively assessed in both groups. RESULTS: The objective treatment response and stable disease were found in 13 patients (86.6%) in the selective internal radiation therapy group and eight patients (66.6%) in the selective internal radiation therapy + peptide receptor radionuclide therapy group. The median overall survival rate was found to be 34.9 months, in the selective internal radiation therapy group and 67.5 months in the selective internal radiation therapy + peptide receptor radionuclide therapy group (P = 0.217). The median progression-free survival data was not reached, and the mean values of progression-free survival were 53.1 ± 9.9 months in the selective internal radiation therapy group, and 27.2 ± 5.9 months in the selective internal radiation therapy + peptide receptor radionuclide therapy group (P = 0.561). Temporary lymphopenia was the most common side effect. Grade 1-2 hepatotoxicity was observed to be 6.6% in the selective internal radiation therapy group, while it was not observed in selective internal radiation therapy + peptide receptor radionuclide therapy group. CONCLUSIONS: In the neuroendocrine tumors with liver-dominant metastatic disease, personalized selective internal radiation therapy and peptide receptor radionuclide therapy and their combinations result in increased survival rates. Selective internal radiation therapy alone could be an effective treatment in patients with liver-limited and -dominant disease.