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Objective To investigate Tau pathology using multimodal biomarkers of neurodegeneration and neurocognition in participants with myotonic dystrophy type 1 (DM1). Methods We recruited twelve participants with DM1 and, for comparison, two participants with Alzheimer’s Disease (AD). Participants underwent cognitive screening and social cognition testing using the Dépistage Cognitif de Québec (DCQ), among other tests. Biomarkers included Tau PET with [18F]-AV-1451, CSF (Aβ, Tau, phospho-Tau), and plasma (Aβ, Tau, Nf-L, GFAP) studies. Results Of the twelve DM1 participants, seven completed the full protocol (Neurocognition 11/12; PET 7/12, CSF 9/12, plasma 12/12). Three DM1 participants were cognitively impaired (CI). On average, CI DM1 participants had lower scores on the DCQ compared to cognitively unimpaired (CU) DM1 participants (75.5/100 vs. 91.4/100) and were older (54 vs. 44 years old) but did not differ in years of education (11.3 vs. 11.1). The majority (6/7) of DM1 participants had no appreciable PET signal. Only one of the CI participants presented with elevated Tau PET SUVR in bilateral medial temporal lobes. This participant was the eldest and most cognitively impaired, and had the lowest CSF Aβ 1-42 and the highest CSF Tau levels, all suggestive of co-existing AD. CSF Tau and phospho-Tau levels were higher in the 3 CI compared to CU DM1 participants, but with a mean value lower than that typically observed in AD. Nf-L and GFAP were elevated in most DM1 participants (9/11 and 8/11, respectively). Finally, CSF phospho-Tau was significantly correlated with plasma Nf-L concentrations. Conclusions and relevance We observed heterogenous cognitive and biomarker profiles in individuals with DM1. While some participants presented with abnormal PET and/or CSF Tau, these patterns were highly variable and only present in a small subset. Although DM1 may indeed represent a non-AD Tauopathy, the Tau-PET tracer used in this study was unable to detect an in vivo Tau DM1 signature in this small cohort. Interestingly, most DM1 participants presented with elevated plasma Nf-L and GFAP levels, suggestive of other, possibly related, central brain alterations which motivate further research. This pioneering study provides novel insights towards the potential relationship between biomarkers and neurocognitive deficits commonly seen in DM1.

OBJECTIVE To determine the prevalence of intra-patient inter-metastatic heterogeneity based on positron emission tomography (PET)/computed tomography (CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) and to determine the prevalence of neuroendocrine disease in these patients and their eligibility for radioligand therapies (RLTs). PATIENTS AND METHODS This multicentre observational prospective clinical study will include 100 patients with mCRPC from five Canadian academic centres. Patients with radiological or biochemical progression and harbouring at least three metastases by conventional imaging will be accrued. Intra-patient inter-metastatic heterogeneity will be determined with triple-tracer imaging using fluorine-18 fluorodeoxyglucose (18 F-FDG), gallium-68-(68 Ga)-prostate-specific membrane antigen (PSMA)-617 and 68 Ga-DOTATATE, which are a glucose analogue, a PSMA receptor ligand and a somatostatin receptor ligand, respectively. The 68 Ga-PSMA-617 and 18 F-FDG PET/CT scans will be performed first. If at least one PSMA-negative/FDG-positive lesion is observed, an additional PET/CT scan with 68 Ga-DOTATATE will be performed. The tracer uptake of individual lesions will be assessed for each PET tracer and patients with lesions presenting discordant uptake profiles will be considered as having inter-metastatic heterogeneous disease and may be offered a biopsy. EXPECTED RESULTS The proposed triple-tracer approach will allow whole-body mCRPC characterisation, investigating the inter-metastatic heterogeneity in order to better understand the phenotypic plasticity of prostate cancer, including the neuroendocrine transdifferentiation that occurs during mCRPC progression. Based on 68 Ga-PSMA-617 or 68 Ga-DOTATATE PET positivity, the potential eligibility of patients for PSMA and DOTATATE-based RLT will be assessed. Non-invasive whole-body determination of mCRPC heterogeneity and transdifferentiation is highly innovative and might establish the basis for new therapeutic strategies. Comparison of molecular imaging findings with biopsies will also link metastasis biology to radiomic features. CONCLUSION This study will add novel, biologically relevant dimensions to molecular imaging: the non-invasive detection of inter-metastatic heterogeneity and transdifferentiation to neuroendocrine prostate cancer by using a multi-tracer PET/CT strategy to further personalise the care of patients with mCRPC.

We highlight emerging uses of artificial intelligence (AI) in the field of theranostics, focusing on its significant potential to enable routine and reliable personalization of radiopharmaceutical therapies (RPTs). Personalized RPTs require patient-specific dosimetry calculations accompanying therapy. Additionally we discuss the potential to exploit biological information from diagnostic and therapeutic molecular images to derive biomarkers for absorbed dose and outcome prediction; toward personalization of therapies. We try to motivate the nuclear medicine community to expand and align efforts into making routine and reliable personalization of RPTs a reality.

68 Ga-DOTATATE PET/CT is indicated for selecting patients for peptide receptor radionuclide therapy (PRRT). Although highly sensitive, the detectability of smaller lesions, particularly in the liver, is lower. We present the case of a 58-year-old man with metastatic well-differentiated pancreatic neuroendocrine tumor whose MRI revealed progression of hepatic metastases. 68 Ga-DOTATATE PET/CT performed to determine eligibility for PRRT did not demonstrate DOTATATE-avid disease within the liver. 18 F-FDG PET/CT was also negative at the liver and the patient proceeded to 177 Lu-DOTATATE PRRT, where multi-time point posttherapy planar imaging and SPECT/CT showed intense uptake in the known liver metastases.

Background PET imaging of glucose metabolism has revealed presymptomatic abnormalities in genetic FTD but has not been explored in MAPT P301L mutation carriers. This study aimed to explore the patterns of presymptomatic hypometabolism and atrophy in MAPT P301L mutation carriers. Methods Eighteen asymptomatic members from five families with a P301L MAPT mutation were recruited to the study, six mutation carriers, and twelve mutation-negative controls. All participants underwent standard behavioural and cognitive assessment as well as [18F]FDG-PET and 3D T1-weighted MRI brain scans. Regional standardised uptake value ratios (SUVR) for the PET scan and volumes calculated from an automated segmentation for the MRI were obtained and compared between the mutation carrier and control groups. Results The mean (standard deviation) estimated years from symptom onset was 12.5 (3.6) in the mutation carrier group with a range of 7 to 18 years. No differences in cognition were seen between the groups, and all mutation carriers had a global CDR plus NACC FTLD of 0. Significant reduction in [18F] FDG uptake in the anterior cingulate was seen in mutation carriers (mean 1.25 [standard deviation 0.07]) compared to controls (1.36 [0.09]). A similar significant reduction was also seen in grey matter volume in the anterior cingulate in mutation carriers (0.60% [0.06%]) compared to controls (0.68% [0.08%]). No other group differences were seen in other regions. Conclusions Anterior cingulate hypometabolism and atrophy are both apparent presymptomatically in a cohort of P301L MAPT mutation carriers. Such a specific marker may prove to be helpful in stratification of presymptomatic mutation carriers in future trials.

Background: Hypometabolism of the posterior cingulate cortex (PCC) is an important diagnostic feature of late-onset, amnestic Alzheimer’s disease (AD) measured with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). However, it is unclear whether PCC hypometabolism has diagnostic value in young-onset, non-amnestic variants of AD, which exhibit less pathology in the hippocampus and default mode network. Objective: Evaluate the prevalence and diagnostic value of PCC hypometabolism in non-amnestic variants of AD. Methods: We retrospectively identified 60 patients with young-onset, atypical dementia who have undergone a detailed clinical evaluation, FDG-PET, and an amyloid biomarker (amyloid-PET or cerebrospinal fluid analysis). We quantitatively analyzed regional hypometabolism in 70 regions of interest (ROI) using the MIMneuro® software. Results: Based on a cut-off of z-score < –1.5 for significant PCC hypometabolism, the prevalence of PCC hypometabolism in non-amnestic variants of AD was 65% compared to 28% in clinical variants of frontotemporal dementia (FTD). The ROI with the maximal hypometabolism was the dominant middle temporal gyrus in the language variant of AD (mean z score –2.28), middle occipital gyrus in PCA (–3.24), middle temporal gyrus in frontal AD (–2.70), and angular gyrus in corticobasal syndrome due to AD (–2.31). The PCC was not among the 10 most discriminant regions between non-amnestic variants of AD versus clinical variants of FTD. Conclusion: We conclude that PCC hypometabolism is not a discriminant feature to distinguish non-amnestic variants of AD from clinical variants of FTD—and should be interpreted with caution in patients with young-onset, non-amnestic dementia.

Background Dead time may affect the accuracy of quantitative SPECT (QPSECT), and thus of dosimetry. The aim of this study was to quantify the effect of dead time on 177Lu-QSPECT and renal dosimetry following peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumours. Methods QSPECT/CT was performed on days 1 and 3 during 564 personalized 177Lu-octreotate cycles in 166 patients. The dead-time data for each scanning time point was compiled. The impact of not correcting QSPECT for the dead time was assessed for the kidney dosimetry. This was also estimated for empiric PRRT by simulating in our cohort a regime of 7.4 GBq/cycle. Results The probability to observe a larger dead time increased with the injected activity. A dead-time loss greater than 5% affected 14.4% and 5.7% of QSPECT scans performed at days 1 and 3, respectively. This resulted in renal absorbed dose estimates that would have been underestimated by more than 5% in 5.7% of cycles if no dead-time correction was applied, with a maximum underestimation of 22.1%. In the simulated empiric regime, this potential dose underestimation would have been limited to 6.2%. Conclusion Dead-time correction improves the accuracy of dosimetry in 177Lu radionuclide therapy and is warranted in personalized PRRT.

Tumour 18F-FDG-uptake is of prognostic value in high-risk and metastatic prostate cancer (PCa). The aim of this study is to investigate the underlying glucose metabolism mechanisms of 18F-FDG-uptake on PET/CT imaging in PCa. Retrospective analysis was conducted for 94 patients diagnosed with a Gleason sum ≥8 adenocarcinoma of the prostate at biopsy between July 2011 and July 2014 who underwent 18F-FDG-PET/CT imaging before radical prostatectomy (RP). 18F-FDG-uptake in primary lesion was measured by a blinded reader using maximum standardised uptake value (SUVmax). GLUT1, GLUT12 and HK2 expression were blindly scored after immunohistochemistry on specimens RP by three pathologists. Correlations between GLUT1, GLUT12 and HK2, and SUVmax were assessed using Spearman’s rank correlation test. Survival probabilities were based on the Kaplan–Meier method. With a median follow-up of 4.5 years, 56% (n = 53) of patients had biochemical recurrence (BCR), 7% (n = 7) progressed to castration-resistant prostate cancer (CRPC) disease, 13% (n = 12) developed metastasis and 6% (n = 6) died. Correlation was found between GLUT1 expression and SUVmax level (r = 0.25, p = 0.02). In addition, SUVmax was significantly higher in tumours with high GLUT1 expression (n = 17, 5.74 ± 1.67) than tumours with low GLUT1 expression (n = 71, 2.68 ± 0.31, p = 0.004). Moreover, a significant association was found between GLUT1 expression levels and SUVmax level (p = 0.005), lymph node status (p = 0.05), volume of cancer (p = 0.01), CRPC disease progression (p = 0.02) and metastasis development (p = 0.04). No significant difference between GLUT12 and HEX2 expression and SUVmax have been found. GLUT1 expression in PCa tumours correlates with 18F-FDG-uptake and poor prognostic factors. These results suggest that this transporter is involved in the molecular mechanism of 18F-FDG-uptake in high-risk PCa and raise interest in targeting metabolic dependencies of PCa cells as a selective anticancer strategy.

Background The accuracy of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to stage prostate cancer (PCa) is limited. However, Gleason 8–10 PCa and more aggressive metastatic PCa have been shown to exhibit a higher glycolytic activity. Objective To evaluate the potential of intraprostatic FDG uptake to prognose Gleason 8–10 PCa patients prior to prostatectomy, based on tumour intrinsic biology. Design, setting, and participants FDG-PET/CT and a bone scan were performed as a staging procedure prior to prostatectomy in 148 consecutive patients diagnosed with PCa with a Gleason sum of ≥8 at biopsy. Outcome measurements and statistical analysis The FDG-PET/CT images were blind reviewed. Lymph node (LN) metastasis and intraprostatic FDG uptake were systematically recorded, and correlated with the patients' clinicopathological characteristics. Results and limitations FDG-PET/CT detected foci of intraprostatic FDG uptake in 66% of patients. An intraprostatic FDG uptake of maximum intraprostatic standardised uptake value (SUVmax) of ≥4.6 was statistically significantly associated with a higher pathological Gleason ≥8, extracapsular extension, seminal vesicle invasion, and pathological LN metastasis. In multivariate analysis, an intraprostatic SUVmax of ≥4.6 was associated with a two-fold increased risk of biochemical recurrence in the year following surgery. Patients with an intraprostatic SUVmax of ≥4.6 had estimated median biochemical recurrence-free survival (BFS) of 11.3mo compared with 49.5mo for those with a lower SUVmax. Finally, high intraprostatic FDG uptake was associated with shorter time to castration resistance following radical prostatectomy (RP). Conclusions Preoperative intraprostatic FDG uptake is an integrator of adverse pathological prognostic factors, predicting BFS and castration resistance following RP in patients with a Gleason score ≥8 PCa at biopsy. These results support the use of preoperative FDG-PET/CT as a tool to distinguish at diagnosis very high–risk Gleason 8–10 PCa patients in whom novel neoadjuvant or adjuvant therapies should be explored. Patient summary This study shows that an increased use of glucose by prostate cancer cells detected by 18 F-fluorodeoxyglucose positron emission tomography molecular imaging can identify aggressive prostate cancers.

To investigate Tau pathology using multimodal biomarkers of neurodegeneration and neurocognition in participants with myotonic dystrophy type 1 (DM1).We recruited twelve participants with DM1 and, for comparison, two participants with Alzheimer's Disease (AD). Participants underwent cognitive screening and social cognition testing using the Dépistage Cognitif de Québec (DCQ), among other tests. Biomarkers included Tau PET with [18F]-AV-1451, CSF (Aβ, Tau, phospho-Tau), and plasma (Aβ, Tau, Nf-L, GFAP) studies.Of the twelve DM1 participants, seven completed the full protocol (Neurocognition 11/12; PET 7/12, CSF 9/12, plasma 12/12). Three DM1 participants were cognitively impaired (CI). On average, CI DM1 participants had lower scores on the DCQ compared to cognitively unimpaired (CU) DM1 participants (75.5/100 vs. 91.4/100) and were older (54 vs. 44 years old) but did not differ in years of education (11.3 vs. 11.1). The majority (6/7) of DM1 participants had no appreciable PET signal. Only one of the CI participants presented with elevated Tau PET SUVR in bilateral medial temporal lobes. This participant was the eldest and most cognitively impaired, and had the lowest CSF Aβ 1-42 and the highest CSF Tau levels, all suggestive of co-existing AD. CSF Tau and phospho-Tau levels were higher in the 3 CI compared to CU DM1 participants, but with a mean value lower than that typically observed in AD. Nf-L and GFAP were elevated in most DM1 participants (9/11 and 8/11, respectively). Finally, CSF phospho-Tau was significantly correlated with plasma Nf-L concentrations.We observed heterogenous cognitive and biomarker profiles in individuals with DM1. While some participants presented with abnormal PET and/or CSF Tau, these patterns were highly variable and only present in a small subset. Although DM1 may indeed represent a non-AD Tauopathy, the Tau-PET tracer used in this study was unable to detect an in vivo Tau DM1 signature in this small cohort. Interestingly, most DM1 participants presented with elevated plasma Nf-L and GFAP levels, suggestive of other, possibly related, central brain alterations which motivate further research. This pioneering study provides novel insights towards the potential relationship between biomarkers and neurocognitive deficits commonly seen in DM1.

177Lu-DOTATATE for neuroendocrine tumours is considered a low-toxicity treatment and may therefore be combined with other pharmaceuticals to potentiate its efficacy. One approach is to add a poly-[ADP-ribose]-polymerase (PARP) inhibitor to decrease the ability of tumour cells to repair 177Lu-induced DNA damage. To decrease the risk of side effects, the sequencing should be optimized according to the tumour-to-normal tissue enhanced dose ratio (TNED). The aim of this study was to investigate how to enhance 177Lu-DOTATATE by optimal timing of the addition of a PARP inhibitor. Biokinetic modelling was performed based on the absorbed dose to the bone marrow, kidneys and tumour, determined from SPECT/CT and planar images from 17 patients treated with 177Lu-DOTATATE. To investigate the theoretical enhanced biological effect of a PARP inhibitor during 177Lu-DOTATATE treatment, the concept of relative biological effectiveness (RBE) was used, and PARP inhibitor administration was simulated over different time intervals. The absorbed dose rate for the tumour tissue demonstrated an initial increase phase until 12 h after infusion followed by a slow decrease. In contrast, the bone marrow showed a rapid initial dose rate decrease. Twenty-eight days after infusion of 177Lu-DOTATATE, the full absorbed dose to the bone marrow and kidney was reached. Using an RBE value of 2 for both the tumour and normal tissues, the TNED was increased compared to 177Lu-DOTATATE alone. According to the modelling, the PARP inhibitor should be introduced approximately 24 h after the start of 177Lu-DOTATATE treatment and be continued for up to four weeks to optimize the TNED. Based on these results, a phase I trial assessing the combination of olaparib and 177Lu-DOTATATE in somatostatin receptor-positive tumours was launched in 2020 (NCT04375267).

Background Accurate QSPECT is crucial in dosimetry-based, personalized radiopharmaceutical therapy with 177Lu and other radionuclides. We compared the quantitative performance of three NaI(Tl)-crystal SPECT/CT systems equipped with low-energy high-resolution collimators from two vendors (Siemens Symbia T6; GE Discovery 670 and NM/CT 870 DR). Methods Using up to 14 GBq of 99mTc in planar mode, we determined the calibration factor and dead-time constant under the assumption that these systems have a paralyzable behaviour. We monitored their response when one or both detectors were activated. QSPECT capability was validated by SPECT/CT imaging of a customized NEMA phantom containing up to 17 GBq of 99mTc. Acquisitions were reconstructed with a third-party ordered subset expectation maximization algorithm. Results The Siemens system had a higher calibration factor (100.0 cps/MBq) and a lower dead-time constant (0.49 μs) than those from GE (75.4–87.5 cps/MBq; 1.74 μs). Activities of up to 3.3 vs. 2.3–2.7 GBq, respectively, were quantifiable by QSPECT before the observed count rate plateaued or decreased. When used in single-detector mode, the QSPECT capability of the former system increased to 5.1 GBq, whereas that of the latter two systems remained independent of the detectors activation mode. Conclusion Despite similar hardware, SPECT/CT systems’ response can significantly differ at high count rate, which impacts their QSPECT capability in a post-therapeutic setting.

We highlight emerging uses of artificial intelligence (AI) in the field of theranostics, focusing on its significant potential to enable routine and reliable personalization of radiopharmaceutical therapies (RPTs). Personalized RPTs require patient-specific dosimetry calculations accompanying therapy. Additionally we discuss the potential to exploit biological information from diagnostic and therapeutic molecular images to derive biomarkers for absorbed dose and outcome prediction; toward personalization of therapies. We try to motivate the nuclear medicine community to expand and align efforts into making routine and reliable personalization of RPTs a reality.

TPS5110 Background: [177Lu]Lu-PSMA-617 improves outcome in men with metastatic, PSMA positive CRPC post androgen pathway inhibitor therapy and taxane chemotherapy compared to standard care (excluding chemotherapy, immunotherapy, radium-223 and investigational drugs; Sartor et al, NEJM 2021). The relative efficacy, adverse event experience and impact on QOL of [177Lu]Lu-PSMA-617 compared to docetaxel chemotherapy in this patient population is unknown. We hypothesize that [177Lu]Lu-PSMA-617 will improve radiographic PFS (rPFS) compared to docetaxel chemotherapy with a favourable safety and tolerability profile. Methods: CCTG PR21 is a Canadian Cancer Trials Group randomized phase II trial with a primary objective to compare rPFS between [177Lu]Lu-PSMA-617 7.4 GBq (+/- 10%) IV q 6 weekly (maximum 6 cycles) versus docetaxel 75 mg/m2 q 3 weekly (maximum 12 cycles). Secondary objectives are to compare the two arms with respect to: 6-month PFS rate (PCWG3 and RECIST 1.1), second rPFS after crossover to the alternate therapy, time to commencement of 3rd line systemic therapy, OS, PSA decline from baseline, clinical benefit rate and adverse events. Tertiary objectives include evaluation of QOL (FACT-P and EQ5D-5L), cost effectiveness, ctDNA and radiographic based prognostic and predictive biomarkers, dosimetry based approach to measurement of [177Lu]Lu-PSMA-617 activity and creation of tissue and image biobanks. Key eligibility criteria include: mCRPC with PSMA positive disease using 18F or 68Ga radionuclide label, progression on ADT + ARPI therapy (using PSA, RECIST 1.1 or PCWG3 criteria) and adequate organ function. Statistical Design: Patients are allocated in 1:1 ratio to [177Lu]Lu-PSMA-617 or docetaxel balanced for stratification factors of ECOG PS, LDH, visceral metastases, previous docetaxel in the castration sensitive setting > 1 year prior to enrollment as well as centre. Assuming a 6-month median rPFS for the control group, the detection of a hazard ratio (HR) of 0.67 with 80% power using a 1-sided 5% level test will require accrual of 200 participants in 24 months with 12-month follow-up to trigger the primary analysis. Conduct to Date: Study activation Dec 17 2020. Enrollment as of January 31 2022: 25. The DSMC last reviewed and recommended continuation of the trial in December 2021. Clinical trial information: NCT04663997.

Peptide receptor radionuclide therapy (PRRT) is mostly administered using a fixed injected activity (IA) per cycle. This empiric regime results in highly variable absorbed doses to the critical organs and undertreatment of the majority of patients. We conceived a personalized PRRT protocol in which the IA is adjusted to deliver a prescribed absorbed dose to the kidney, with the aim to safely increase tumour irradiation. We herein report on the initial results of our prospective study of personalized PRRT, the P-PRRT Trial (NCT02754297). PRRT-naive patients with progressive and/or symptomatic neuroendocrine tumour (NET) were scheduled to receive a four-cycle induction course of 177Lu-octreotate with quantitative SPECT/CT-based dosimetry. The IA was personalized according to the glomerular filtration rate and the body surface area for the first cycle, and according to the prior renal Gy/GBq for the subsequent cycles. The prescribed renal absorbed dose of 23 Gy was reduced by 25–50% in case of significant renal or haematological impairment. Responders were allowed to receive consolidation or maintenance cycles, for each of which 6 Gy to the kidney were prescribed. We simulated the empiric PRRT regime by fixing the IA at 7.4 GBq per cycle, with the same percentage reductions as above. Radiological, molecular imaging, biochemical, and quality of life responses, as well as safety, were assessed. Fifty-two patients underwent 171 cycles. In 34 patients who completed the induction course, a median cumulative IA of 36.1 (range, 6.3–78.6) GBq was administered, and the median cumulative kidney and maximum tumour absorbed doses were 22.1 (range, 8.3–24.3) Gy and 185.7 (range: 15.2–443.1) Gy respectively. Compared with the simulated fixed-IA induction regime, there was a median 1.26-fold increase (range, 0.47–2.12 fold) in the cumulative maximum tumour absorbed dose, which was higher in 85.3% of patients. In 39 assessable patients, the best objective response was partial response in nine (23.1%), minor response in 14 (35.9%), stable disease in 13 (33.3%) and progressive disease in three patients (7.7%). In particular, 11 of 13 patients (84.6%) with pancreatic NET had partial or minor response. The global health status/quality of life score significantly increased in 50% of patients. Acute and subacute side-effects were all of grade 1 or 2, and the most common were nausea (in 32.7% of patients) and fatigue (in 30.8% of patients) respectively. Subacute grade 3 or 4 toxicities occurred in less than 10% of patients, with the exception of lymphocytopenia in 51.9% of patients, without any clinical consequences however. No patient experienced severe renal toxicity. Personalized PRRT makes it possible to safely increase tumour irradiation in the majority of patients. Our first results indicate a favourable tolerance profile, which appears similar to that of the empiric regime. The response rates are promising, in particular in patients with NET of pancreatic origin.

INTRODUCTION: In this study, we compared (18)F-fluorodeoxyglucose ((18)F-FDG)-positron emission tomography/computed tomography (PET/CT) and bone scintigraphy accuracies for the detection of bone metastases for primary staging in high-grade prostate cancer (PCa) patients to determine if (18)F-FDG-PET/CT could be used alone as a staging modality. METHODS: Men with localized high-grade PCa (n=256, Gleason 8–10, International Society of Urological Pathology [ISUP] grades 4 or 5) were imaged with bone scintigraphy and (18)F-FDG-PET/CT. We compared, on a per-patient basis, the accuracy of the two imaging modalities, taking inter-modality agreement as the standard of truth (SOT). RESULTS: (18)F-FDG-PET/CT detected at least one bone metastasis in 33 patients compared to only 26 with bone scan. Of the seven false-negative bone scintigraphies, four (57.1%) were solitary metastases (monometastatic), three (42.9%) were oligometastatic (2–4 lesions), and none were plurimetastatic (>4 lesions). Compared to SOT, (18)F-FDG-PET/CT showed higher sensitivity and accuracy than bone scintigraphy (100% vs. 78.8%, and 98.7% vs. 98.2%) for the detection of skeletal lesions. CONCLUSIONS: (18)F-FDG-PET/CT appears similar or better than conventional bone scans to assess for bone metastases in patients newly diagnosed with high-grade PCa. Since intraprostatic FDG uptake is also a biomarker for failure of radical prostatectomy and that FDG-PET/CT has been shown to be accurate in detecting PCa lymph node metastasis, FDG-PET/CT has the potential to be used as the sole preoperative staging modality in high-grade PCa.

Additional file 1: Supplementary Figure 1. Receiver operating characteristic (ROC) curves illustrate the capacity for A) anterior cingulate SUVR of [18F] FDG, B) anterior cingulate volume expressed as a percentage of TIV and C) combined anterior cingulate SUVR and volume biomarkers to distinguish P301L MAPT mutation carriers from controls.

Background Personalization of 177Lu-based radionuclide therapy requires implementation of dosimetry methods that are both accurate and practical enough for routine clinical use. Quantitative single-photon emission computed tomography/computed tomography (QSPECT/CT) is the preferred scanning modality to achieve this and necessitates characterizing the response of the camera, and calibrating it, over the full range of therapeutic activities and system capacity. Various methods to determine the camera calibration factor (CF) and the deadtime constant (τ) were investigated, with the aim to design a simple and robust protocol for quantitative 177Lu imaging. Methods The SPECT/CT camera was equipped with a medium energy collimator. Multiple phantoms were used to reproduce various attenuation conditions: rod sources in air or water-equivalent media, as well as a Jaszczak phantom with inserts. Planar and tomographic images of a wide range of activities were acquired, with multiple energy windows for scatter correction (double or triple energy window technique) as well as count rate monitoring over a large spectrum of energy. Dead time was modelled using the paralysable model. CF and τ were deduced by curve fitting either separately in two steps (CF determined first using a subset of low-activity acquisitions, then τ determined using the full range of activity) or at once (both CF and τ determined using the full range of activity). Total or segmented activity in the SPECT field of view was computed. Finally, these methods were compared in terms of accuracy to recover the known activity, in particular when planar-derived parameters were applied to the SPECT data. Results The SPECT camera was shown to operate as expected on a finite count rate range (up to ~ 350 kcps over the entire energy spectrum). CF and τ from planar (sources in air) and SPECT segmented Jaszczak data yielded a very good agreement (CF < 1% and τ < 3%). Determining CF and τ from a single curve fit made dead-time-corrected images less prone to overestimating recovered activity. Using triple-energy window scatter correction while acquiring one or more additional energy window(s) to enable wide-spectrum count rate monitoring (i.e. ranging 55–250 or 18–680 keV) yielded the most consistent results across the various geometries. The final, planar-derived calibration parameters for our system were a CF of 9.36 ± 0.01 cps/MBq and a τ of 0.550 ± 0.003 μs. Using the latter, the activity in a Jaszczak phantom could be quantified by QSPECT with an accuracy of 0.02 ± 1.10%. Conclusions Serial planar acquisitions of sources in air using an activity range covering the full operational capacity of the SPECT/CT system, with multiple energy windows for wide-spectrum count rate monitoring, and followed by simultaneous determination of CF and τ using a single equation derived from the paralysable model, constitutes a practical method to enable accurate dead-time-corrected QSPECT imaging in a post-177Lu radionuclide therapy setting.

TumourRetrospective analysis was conducted for 94 patients diagnosed with a Gleason sum ≥8 adenocarcinoma of the prostate at biopsy between July 2011 and July 2014 who underwentWith a median follow-up of 4.5 years, 56% (n = 53) of patients had biochemical recurrence (BCR), 7% (n = 7) progressed to castration-resistant prostate cancer (CRPC) disease, 13% (n = 12) developed metastasis and 6% (n = 6) died. Correlation was found between GLUT1 expression and SUVmax level (r = 0.25, p = 0.02). In addition, SUVGLUT1 expression in PCa tumours correlates with

For patients with inoperable neuroendocrine tumors (NETs) expressing somatostatin receptors, peptide receptor radionuclide therapy (PRRT) with 177Lu-[DOTA0-Tyr3]-octreotate (177Lu-octreotate) is one of the most promising targeted therapeutic options but it rarely achieves cure. Therefore, different approaches are being tested to increase the efficacy of 177Lu-octreotate PRRT in NET patients. Using the gastroenteropancreatic BON-1 and the bronchopulmonary NCI-H727 as NET cell models, here we report that pharmacological inhibitors of DNA repair-associated enzyme poly(ADP-ribose) polymerase-1 (PARPi) potentiate the cytotoxic effect of 177Lu-octreotate on 2D monolayer and 3D spheroid models of these two types of NET cells. PARPi mediates this effect by enhancing 177Lu-octreotate-induced cell cycle arrest and cell death. Thus, the use of PARPi may offer a novel option for improving the therapeutic efficacy of 177Lu-octreotate PRRT of NETs.

Background and importance Olfactory neuroblastoma, also known as esthesioneuroblastoma (ENB), is a malignant neoplasm with an unpredictable behavior. Currently, the widely accepted treatment is inductive chemotherapy, with or without surgery, followed by radiotherapy. Since data on genetics and molecular alterations of ENB are lacking, there is no standard molecularly targeted therapy. However, ENB commonly expresses the somatostatin receptor (SSTR) that is also expressed by neuroendocrine tumors. Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogues, such as 177Lu-octreotate, is an effective treatment for the latter. We present the complex neuroradiological and neuropathological changes associated with 177Lu-octreotate treatment of a patient with a highly treatment-resistant ENB. Clinical presentation A 60-yr-old male presented with an ENB that recurred after chemotherapy, surgery, stereotactic radiosurgery, and immunotherapy. Pathology revealed a Hyams grade 3 ENB and the tumor had metastasized to lymph nodes. Tumor SSTR expression was seen on 68Ga-octreotate positron emission tomography (PET)/computed tomography (CT), suggesting that PRRT may be an option. He received 4 cycles of 177Lu-octreotate over 6 mo, with a partial response of all lesions and symptomatic improvement. Four months after the last PRRT cycle, 2 of the lesions rapidly relapsed and were successfully resected. Three months later, 68Ga-octreotate PET/CT and magnetic resonance imaging indicate no progression of the disease. Conclusion We describe imaging changes associated with 177Lu-octreotate PRRT of relapsing ENB. To our knowledge, this is the first report describing neuropathological changes associated with this treatment. PRRT is a promising therapeutic option to improve the disease control, and potentially, the survival of patients with refractory ENB.

Peptide receptor radionuclide therapy (PRRT) with

The incidence of neuroendocrine tumours (NETs) is increasing, but curative therapeutic options are limited because diagnosis is often delayed until the tumour has metastasized. Peptide receptor radionuclide therapy (PRRT) is among the most effective therapeutic options for metastatic NETs because of targeted delivery of radioactivity to the tumour via the somatostatin receptor (SSTR) and relatively low systemic toxicity. However, current PRRT regimes result in palliation rather than cure, and higher doses of PRRT that might achieve remission would also be too toxic to the patients. Therefore, there is a need to improve PRRT of NETs by combining it with other agents to achieve maximum benefits from the internal radiation therapy, while sparing non-target organs from radiation toxicity. Here we review various current and potential combination strategies to improve 177Lu-octreotate-based PRRT of NET, some of which could also apply to other radionuclide therapies. These strategies include co-administered drugs that improve delivery of the radiopharmaceutical via increased tumour perfusion or through increased SSTR density at tumour surface. Other combinations are aimed at enhancing the biological effects of the radiation-induced DNA damage in tumour cells or generating additional DNA damage burden to effectively increase the cytotoxicity of PRRT. We also propose an algorithm for stratifying NET patients to receive or not combination therapies with PRRT. Considering that PRRT and many of these combination agents are already used for treating patients with NET and other cancers, the proposed strategies to improve the efficacy of PRRT could be rapidly translated into the clinic.

Background Routine dosimetry is essential for personalized 177Lu-octreotate peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs), but practical and robust dosimetry methods are needed for wide clinical adoption. The aim of this study was to assess the accuracy and inter-observer reproducibility of simplified dosimetry protocols based on quantitative single-photon emission computed tomography (QSPECT) with a limited number of scanning time points. We also updated our personalized injected activity (IA) prescription scheme. Methods Seventy-nine NET patients receiving 177Lu-octreotate therapy (with a total of 279 therapy cycles) were included in our study. Three-time-point (3TP; days 0, 1, and 3) QSPECT scanning was performed following each therapy administration. Dosimetry was obtained using small volumes of interest activity concentration sampling for the kidney, the bone marrow and the tumor having the most intense uptake. Accuracy of the simplified dosimetry based on two-time-point (2TP; days 1 and 3, monoexponential fit) or a single-time-point (1TPD3; day 3) scanning was assessed, as well as that of hybrid methods based on 2TP for the first cycle and 1TP (day 1 or 3; 2TP/1TPD1 and 2TP/1TPD3, respectively) or no imaging at all (based on IA only; 2TP/no imaging (NI)) for the subsequent induction cycles. The inter-observer agreement was evaluated for the 3TP, 2TP, and hybrid 2TP/1TPD3 methods using a subset of 60 induction cycles (15 patients). The estimated glomerular filtration rate (eGFR), body size descriptors (weight, body surface area (BSA), lean body weight (LBW)), and products of both were assessed for their ability to predict IA per renal absorbed dose at the first cycle. Results The 2TP dosimetry estimates correlated highly with those from the 3TP data for all tissues (Spearman r > 0.99, P

The peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA-octreotate (LuTate) is recommended for different types of neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination with chemotherapy improves objective response to LuTate in NET patients and here we characterized chemotherapy-induced upregulation of SSTR2 receptors as a cause for this improved response to LuTate. The NET cell lines with low (BON-1) or relatively high (NCI-H727) SSTR2-expression levels, and non-NET cancer and normal cells were treated with chemotherapeutic drugs and assessed for upregulation of SSTR2. We report that an exposure to low or high doses of drugs, such as temozolomide for 24 h or 5 day results in upregulation of SSTR2 between 3&ndash, 7 days, increased LuTate uptake and decreased rate of cell proliferation. This effect is at the level of SSTR2-mRNA and is more pronounced in low SSTR2 expressing BON-1 than in high SSTR2 expressing NCI-H727 or non-NET cancer or normal cells. Thus, a properly timed pre-treatment with low-dose chemotherapy could not only improve therapeutic efficacy of LuTate in NET patients who are presently eligible for PRRT, but also allow PRRT to be administered to patients with low SSTR-expressing NETs, who would otherwise not respond to this modality because of insufficient radiation delivery.

1006 Introduction: Prostate-specific membrane antigen (PSMA)-ligand PET imaging has shown to be valuable for imaging men with prostate cancer. The problem of inter-observer variability related to subjective visual analysis and the lack of objective quantitative methods make it difficult to compare results from different centers. There is therefore a need for automated methods to quantify PET/CT findings. The aim of this study was to develop an artificial intelligence (AI) tool for detection and quantification of primary prostate tumors, bone metastases, and lymph node lesions in PSMA PET/CT studies, and to evaluate the effect of the AI tool on inter-observer variability. Methods: The test group consisted of 10 patients referred for PSMA PET/CT for initial staging at Skane University Hospital, Lund and Malmo, Sweden during 2019-2020. Patients were administered with 4 MBq/kg [18F]-PSMA-1007 and after 2 h scanned on a Discovery MI PET/CT (GE healthcare, Milwaukee, WI).Three nuclear medicine specialists independently segmented primary prostate tumors, bone metastases, and lymph node lesions in the 10 studies, first without AI support and then, more than eight weeks later, with segmentations proposed by the AI tool. The new AI tool relies heavily on the CT-based organ segmentation tool from work by Tragardh et al. (EJNMMI Phys. 2020;7:51). To reduce the problem of PET/CT misalignment, each pixel is assigned to a close local maximum using a flooding algorithm. Uptake in a pixel is assumed to originate from the organ of the corresponding local maximum.Prostate tumors: The lesion threshold is set to standard uptake value (SUV) 2 + first quartile of the prostate uptake, but at most SUV 5. Any high uptake region connected to the prostate is included unless it originates from bone, bladder or gastrointestinal tract.Bone metastases: For each of the following groups, vertebra, rib, scapula, radius, fibula, patella, hand, humerus, clavicle, tibia, foot, hip, femur, ulna and sternum, the lesion threshold is set to SUV 3 * median bone uptake, restrained between SUV 2 and SUV 10. Lymph node lesions: The model from Borrelli et al. (Clin Physiol Funct Imaging. 2021;41:62) was used to directly segment lymph node lesions. Finally, lesions with total lesion uptake (TLU) less than 2.0 were removed. The McNemar test was used to analyze the difference in patients with increased and decreased variability between observers without and with support of AI. Results: To measure the inter-observer variability in TLU measurements for each patient, the relative difference between pairs of observers was computed. For both prostate TLU and bone TLU, the average of the three relative differences, decreased for all 10 patients with the support of AI (p=0.004). For lymph node lesions, the average relative differences decreased for 7 patients, increased for 2 patients and was unchanged in 1 patient with the support of AI (p=0.18). Conclusions: Physicians supported by an AI tool for automated quantification of PSMA-PET/CT studies showed significantly less inter-observer variability in the quantification of primary prostate tumors and bone metastases than when performing a completely manual analysis. This AI tool may help in facilitating comparison of studies from different centers, pooling data within multicenter trials and performing meta-analysis. The AI tool developed in this project is available upon reasonable request for research purposes at www.recomia.org.

Diagnosis of atypical/unclear dementia is often difficult and this delays treatment initiation. Several authors have shown that beyond standard dementia workup, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) reduces the number of unclear diagnoses, leads to earlier treatment, and has a beneficial impact on families. However, it is not uncommon that the FDG-PET findings are equivocal in this setting. For those cases, a repeat FDG-PET may clarify the diagnosis and prevent treatment delay. We retrospectively assessed the clinical impact of a repeat FDG-PET in 59 patients with atypical/unclear dementia syndromes and inconclusive initial FDG-PET. Changes in primary diagnosis, diagnostic confidence, and management following the second FDG-PET were examined. Conducting a second FDG-PET reduced the number of unclear diagnoses from 80% to 34% , led to diagnostic change in 24% of cases, and treatment modification in 22% of patients. Overall, the clinical impact was higher when initial diagnostic confidence was low and the second FDG-PET repeated ≥12 months after the first one. In tertiary care memory clinic settings, when diagnostic incertitude persists despite extensive evaluation and an equivocal FDG-PET, repeating the FDG-PET 12 months later can greatly clarify the diagnosis and improve management.

Peptide receptor radionuclide therapy (PRRT) is mostly administered using a fixed injected activity (IA) per cycle. This empiric regime results in highly variable absorbed doses to the critical organs and undertreatment of the majority of patients. We conceived a personalized PRRT protocol in which the IA is adjusted to deliver a prescribed absorbed dose to the kidney, with the aim to safely increase tumour irradiation. We herein report on the initial results of our prospective study of personalized PRRT, the P-PRRT Trial (NCT02754297).PRRT-naïve patients with progressive and/or symptomatic neuroendocrine tumour (NET) were scheduled to receive a four-cycle induction course ofFifty-two patients underwent 171 cycles. In 34 patients who completed the induction course, a median cumulative IA of 36.1 (range, 6.3-78.6) GBq was administered, and the median cumulative kidney and maximum tumour absorbed doses were 22.1 (range, 8.3-24.3) Gy and 185.7 (range: 15.2-443.1) Gy respectively. Compared with the simulated fixed-IA induction regime, there was a median 1.26-fold increase (range, 0.47-2.12 fold) in the cumulative maximum tumour absorbed dose, which was higher in 85.3% of patients. In 39 assessable patients, the best objective response was partial response in nine (23.1%), minor response in 14 (35.9%), stable disease in 13 (33.3%) and progressive disease in three patients (7.7%). In particular, 11 of 13 patients (84.6%) with pancreatic NET had partial or minor response. The global health status/quality of life score significantly increased in 50% of patients. Acute and subacute side-effects were all of grade 1 or 2, and the most common were nausea (in 32.7% of patients) and fatigue (in 30.8% of patients) respectively. Subacute grade 3 or 4 toxicities occurred in less than 10% of patients, with the exception of lymphocytopenia in 51.9% of patients, without any clinical consequences however. No patient experienced severe renal toxicity.Personalized PRRT makes it possible to safely increase tumour irradiation in the majority of patients. Our first results indicate a favourable tolerance profile, which appears similar to that of the empiric regime. The response rates are promising, in particular in patients with NET of pancreatic origin.

In recent years, major advances in molecular imaging of prostate cancers (PCa) were made with the development and clinical validation of highly accurate PET tracers to stage and restage the disease. Prostate-specific membrane antigen (PSMA) is a transmembrane protein highly expressed in PCa, and its expression has led to the development of PSMA-binding radiopharmaceuticals for molecular imaging or radioligand therapy (RLT). We herein review the recent literature published on diagnostic and therapeutic (i.e. theranostic) PSMA tracers.Development in small PSMA-targeted molecules labeled with gallium-68 and fluorine-18 show promising results for primary staging and detection of disease at biochemical recurrence using PET/computed tomography (PET/CT). Studies show a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and bone scan) or choline PET tracers, especially for restaging after prostate-specific antigen failure following loco-regional therapy. In addition, some PSMA tracers can be labeled with beta-minus and alpha particle emitters, yielding encouraging response rates and low toxicity, and potentially offering a new line of targeted therapy for metastatic castration-resistant PCa.PSMA-targeted tracers have shown unprecedented accuracy to stage and restage PCa using PET/CT. Given their specific biodistribution toward PCa tissue, PSMA RLT now offers new therapeutic possibilities to target metastatic PCa. Prospective multicenter randomized studies investigating the clinical impact of PSMA-targeted molecules are urgently needed.

Background: Camera calibration, which translates reconstructed count map into absolute activity map, is a prerequisite procedure for quantitative SPECT imaging. Both planar and tomographic scans using different phantom geometries have been proposed for the determination of the camera calibration factor (CF). However, there is no consensus on which approach is the best. The aim of this study is to evaluate all these calibration methods, compare their performance, and propose a practical and accurate calibration method for SPECT quantitation of therapeutic radioisotopes. Twenty-one phantom experiments (Siemens Symbia SPECT/CT) and 12 Monte Carlo simulations (GATE v6.1) using three therapy isotopes (131I, 177Lu, and 188Re) have been performed. The following phantom geometries were used: (1) planar scans of point source in air (PS), (2) tomographic scans of insert(s) filled with activity placed in non-radioactive water (HS + CB), (3) tomographic scans of hot insert(s) in radioactive water (HS + WB), and (4) tomographic scans of cylinders uniformly filled with activity (HC). Tomographic data were reconstructed using OSEM with CT-based attenuation correction and triple energy window (TEW) scatter correction, and CF was determined using total counts in the reconstructed image, while for planar scans, the photopeak counts, corrected for scatter and background with TEW, were used. Additionally, for simulated data, CF obtained from primary photons only was analyzed. Results: For phantom experiments, CF obtained from PS and HS + WB agreed to within 6% (below 3% if experiments performed on the same day are considered). However, CF from HS + CB exceeded those from PS by 4–12%. Similar trend was found in simulation studies. Analysis of CFs from primary photons helped us to understand this discrepancy. It was due to underestimation of scatter by the TEW method, further enhanced by attenuation correction. This effect becomes less important when the source is distributed over the entire phantom volume (HS + WB and HC). Conclusions: Camera CF could be determined using planar scans of a point source, provided that the scatter and background contributions are removed, for example using the clinically available TEW method. This approach is simple and yet provides CF with sufficient accuracy (~ 5%) to be used in clinics for radiotracer quantification.

The accuracy ofTo evaluate the potential of intraprostatic FDG uptake to prognose Gleason 8-10 PCa patients prior to prostatectomy, based on tumour intrinsic biology.FDG-PET/CT and a bone scan were performed as a staging procedure prior to prostatectomy in 148 consecutive patients diagnosed with PCa with a Gleason sum of ≥8 at biopsy.The FDG-PET/CT images were blind reviewed. Lymph node (LN) metastasis and intraprostatic FDG uptake were systematically recorded, and correlated with the patients' clinicopathological characteristics.FDG-PET/CT detected foci of intraprostatic FDG uptake in 66% of patients. An intraprostatic FDG uptake of maximum intraprostatic standardised uptake value (SUVmax) of ≥4.6 was statistically significantly associated with a higher pathological Gleason ≥8, extracapsular extension, seminal vesicle invasion, and pathological LN metastasis. In multivariate analysis, an intraprostatic SUVmax of ≥4.6 was associated with a two-fold increased risk of biochemical recurrence in the year following surgery. Patients with an intraprostatic SUVmax of ≥4.6 had estimated median biochemical recurrence-free survival (BFS) of 11.3mo compared with 49.5mo for those with a lower SUVmax. Finally, high intraprostatic FDG uptake was associated with shorter time to castration resistance following radical prostatectomy (RP).Preoperative intraprostatic FDG uptake is an integrator of adverse pathological prognostic factors, predicting BFS and castration resistance following RP in patients with a Gleason score ≥8 PCa at biopsy. These results support the use of preoperative FDG-PET/CT as a tool to distinguish at diagnosis very high-risk Gleason 8-10 PCa patients in whom novel neoadjuvant or adjuvant therapies should be explored.This study shows that an increased use of glucose by prostate cancer cells detected by

For patients with inoperable neuroendocrine tumors (NETs) expressing somatostatin receptors, peptide receptor radionuclide therapy (PRRT) with 177Lu-[DOTA0-Tyr3]-octreotate (177Lu-octreotate) is one of the most promising targeted therapeutic options but it rarely achieves cure. Therefore, different approaches are being tested to increase the efficacy of 177Lu-octreotate PRRT in NET patients. Using the gastroenteropancreatic BON-1 and the bronchopulmonary NCI-H727 as NET cell models, here we report that pharmacological inhibitors of DNA repair-associated enzyme poly(ADP-ribose) polymerase-1 (PARPi) potentiate the cytotoxic effect of 177Lu-octreotate on 2D monolayer and 3D spheroid models of these two types of NET cells. PARPi mediates this effect by enhancing 177Lu-octreotate-induced cell cycle arrest and cell death. Thus, the use of PARPi may offer a novel option for improving the therapeutic efficacy of 177Lu-octreotate PRRT of NETs.

Although intrapatient heterogeneity of prostate cancer (PCa) has recently been characterized via genomic and transcriptomic studies, the heterogeneity of systemic treatment responses has yet to be reported or imaged. Our objective was to evaluate the intrapatient intermetastasis response to systemic treatment among patients with metastatic PCa. We evaluated the metabolic response for each individual metastatic lesion ( n =165) in 15 patients with metastatic PCa who underwent 18 F-fluorodeoxyglucose positron emission tomography/computed tomography before and at least 3 mo after initiation of a systemic therapy that did not change in that period. Intermetastasis heterogeneity was defined as opposite metabolic responses for at least two metastases from the same compartment (bone or soft tissue) between the two time points. We found intrapatient intermetastasis response heterogeneity in 40% of the cases in our retrospective series. Our results suggest that systemic therapies can induce heterogeneous responses among individual metastases in patients with PCa, supporting the polyclonal evolution of PCa in advanced disease. Molecular imaging may thus be useful in identifying clinical resistance early after therapy initiation and could also allow targeted biopsy of resistant clones for molecular analysis. Patient summary Systemic therapies can lead to heterogeneous responses in individual metastases of prostate cancer in a patient. Molecular imaging may be useful for identifying heterogeneity and could allow targeted biopsy for molecular analysis or therapy.

Background: The aim of the study is to assess accuracy of activity quantification of 177Lu studies performed according to recommendations provided by the committee on Medical Internal Radiation Dose (MIRD) pamphlets 23 and 26. The performances of two scatter correction and three segmentation methods were compared. Additionally, the accuracy of tomographic and planar methods for determination of the camera normalization factor (CNF) was evaluated. Eight phantoms containing inserts of different sizes and shapes placed in air, water, and radioactive background were scanned using a Siemens SymbiaT SPECT/CT camera. Planar and tomographic scans with 177Lu sources were used to measure CNF. Images were reconstructed with our SPEQToR software using resolution recovery, attenuation, and two scatter correction methods (analytical photon distribution interpolated (APDI) and triple energy window (TEW)). Segmentation was performed using a fixed threshold method for both air and cold water scans. For hot water experiments three segmentation methods were compared as folows: a 40% fixed threshold, segmentation based on CT images, and our iterative adaptive dual thresholding (IADT). Quantification error, defined as the percent difference between experimental and true activities, was evaluated. Results: Quantification error for scans in air was better for TEW scatter correction (100 ml) were obtained when APDI and IADT were used for scatter correction and segmentation, respectively. Additionally, we showed that planar acquisitions with scatter correction and tomographic scans provide similar CNF values. This is an important finding because planar acquisitions are easier to perform than tomographic scans. TEW and APDI resulted in similar quantification errors with APDI showing a small advantage for objects placed in medium with non-uniform density. Conclusions: Following the MIRD recommendations for data acquisition and reconstruction resulted in accurate activity quantification (errors