Image-based dosimetry for [225Ac]Ac-PSMA-I&T therapy and the effect of daughter-specific pharmacokinetics.

PURPOSE: Although 221Fr and 213Bi have sufficient gamma emission probabilities, quantitative SPECT after [225Ac]Ac-PSMA-I&T therapy remains challenging due to low therapeutic activities. Furthermore, 221Fr and 213Bi may underlie a different pharmacokinetics due to alpha recoil. We conducted a quantitative SPECT study and a urine analysis to investigate the pharmacokinetics of 221Fr and 213Bi and the impact on image-based lesion and kidney dosimetry. METHODS: Five patients (7.7 ± 0.2 MBq [225Ac]Ac-PSMA-I&T) underwent an abdominal SPECT/CT (1 h) at 24 and 48 h (Siemens Symbia T2, high-energy collimator, 440 keV/218 keV (width 20%), 78 keV (width 50%)). Quantitative SPECT was reconstructed using MAP-EM with attenuation and transmission-dependent scatter corrections and resolution modelling. Time-activity curves for kidneys (CT-based) and lesions (80% isocontour 24 h) were fitted mono-exponentially. Urine samples collected along with each SPECT/CT were measured in a gamma counter until secular equilibrium was reached. RESULTS: Mean kidney and lesion effective half-lives were as follows: 213Bi, 27 ± 6/38 ± 10 h; 221Fr, 24 ± 6/38 ± 11 h; 78 keV, 23 ± 7/39 ± 13 h. The 213Bi-to-221Fr kidney SUV ratio increased by an average of 9% from 24 to 48 h. Urine analysis revealed an increasing 213Bi-to-225Ac ratio (24 h, 0.98 ± 0.15; 48 h, 1.08 ± 0.09). Mean kidney and lesion absorbed doses were 0.17 ± 0.06 and 0.36 ± 0.1 Sv RBE = 5 /MBq using 221Fr and 213Bi SPECT images, compared to 0.16 ± 0.05/0.18 ± 0.06 and 0.36 ± 0.1/0.38 ± 0.1 Sv RBE = 5 /MBq considering either the 221Fr or 213Bi SPECT. CONCLUSION: SPECT/CT imaging and urine analysis showed minor differences of up to 10% in the daughter-specific pharmacokinetics. These variances had a minimal impact on the lesion and kidney dosimetry which remained within 8%.

Neuroendocrine liver metastases treated using transarterial radioembolization: Identification of prognostic parameters at 68Ga-DOTATATE PET/CT.

PURPOSE: To identify prognostic clinical and imaging parameters for patients with neuroendocrine liver metastases (NELMs) undergoing transarterial radioembolization (TARE). MATERIALS AND METHODS: Forty-seven patients (27 men; mean age, 64 years) with NELMs who received TARE, along with pre-procedure liver MRI and 68Ga-DOTATATE positron emission tomography/computed tomography were included. Apparent diffusion coefficient and standardized uptake value (SUV) of three liver metastases, normal spleen and liver were measured. SUVmax or SUVmean were used for the calculation of tumor-to-organ ratios (tumor-to-spleen and tumor-to-liver ratios) using all possible combinations (including SUVmax/SUVmax, SUVmax/SUVmean, and SUVmean/SUVmean). Clinical parameters (hepatic tumor-burden, presence of extra-hepatic metastases, chromograninA, Ki-67 and bilirubin levels) were assessed. Overall survival, progression-free survival (PFS) and hepatic progression-free survival (HPFS) were calculated using Kaplan-Meier curves. RESULTS: Median overall survival, PFS and HPFS were 49.6, 13.1 and 28.3 months, respectively. In multivariable Cox regression analysis, low Ki-67 (≤ 5%), low hepatic tumor-burden (< 10%), absence of extrahepatic metastases, and increased Tmean/Lmax ratio were significant prognostic factors of longer overall survival and HPFS. High baseline chromograninA (> 1330 ng/mL) was associated with shorter HPFS. Tmean/Lmax > 1.9 yielded a median overall survival of 69 vs. 33 months (P < 0.04), and a median HPFS of 30 vs. 19 months (P = 0.09). For PFS, high baseline SUVmax of NELMs was the single significant parameter in the multivariable model. SUVmax > 28 resulted in a median PFS of 16.9 vs. 6.5 months, respectively (P = 0.001). CONCLUSION: High preinterventional Tmean/Lmax ratios, and high SUVmax on 68Ga-DOTATATE positron emission tomography/computed tomography seem to have prognostic value in patients with NELMs undergoing TARE, potentially aiding patient selection and management alongside conventional variables.

Primary presentation and clinical course of pediatric and adolescent patients with differentiated thyroid carcinoma after radioiodine therapy.

Introduction: Differentiated thyroid carcinoma (DTC) in childhood and during adolescence is extremely rare. Pediatric DTC commonly presents with advanced disease at diagnosis including a high prevalence of cervical lymph node metastases and pulmonary metastases. Studies in children with DTC are limited. Therefore, we aimed to evaluate the initial presentation, effectiveness of radioiodine therapy (RIT), and long-term outcome of prepubertal in comparison to pubertal/postpubertal patients. Methods: Eighty-five pediatric and young patients aged 6.4 to 21.9 years with histopathologically confirmed DTC were retrospectively included. They all underwent total thyroidectomy followed by RIT. Initial presentation and outcome of prepubertal and pubertal/postpubertal patients were compared 1 year after RIT, during follow-up, and at the last visit of follow-up. Results: Prepubertal patients presented with significantly higher T and M stages. One year after RIT, 42/81 (52%) patients still presented with evidence of disease (ED). During follow-up of a median of 7.9 years, prepubertal patients were less often in complete remission (58% vs. 82% in pubertal patients). At the last visit of follow-up, 19/80 (24%) patients still had ED without statistical differences between the two groups (42% prepubertal vs. 18% pubertal/postpubertal, p-value 0.06). None of our patients died disease-related over the observed period. Conclusion: Prepubertal children with DTC presented with a more advanced tumor stage at the initial presentation. During follow-up, they present more often with ED. However, at the end of our study, we did not observe statistically relevant differences in patient outcomes between the prepubertal and pubertal/postpubertal groups.

Evaluation of MRI in the diagnostic accuracy of extrahepatic metastases in neuroendocrine tumors in comparison with the reference standard somatostatin-receptor-PET/CT.

Purpose: The aim of this study was to compare the diagnostic performance of different sets of MR sequences in detecting extrahepatic disease of NETs on routine liver magnetic resonance imaging (MRI). Method: One hundred twenty-seven patients with NETs with and without hepatic and extrahepatic metastases who underwent liver MRI and SSTR-PET/CT were retrospectively analyzed. Two radiologists evaluated in consensus in four sessions: (1) non-contrast T1w+T2w (NC), (2) NC+DWI, (3) NC+ contrast-enhanced T1w (CE), and (4) NC+DWI+CE the presence and number of metastases (lymph nodes, bone, peritoneal surface, lung base, and abdominal organ). Sensitivity, specificity, positive, and negative predictive value for detection of metastases were calculated for each session in a patient-based manner; detection and error rates were calculated for lesion-based analysis. Comparison between the MR-sessions and positron emission tomography-computed tomography (PET/CT) was performed with the McNemar test. Results: Regarding all 1,094 lesions detected in PET/CT, NC+DWI, and NC, CE+DWI identified most true-positive lesions 779 (71%) and 775 (71%), respectively. Patient-based analysis revealed significantly higher sensitivity by NC+DWI (85%) than NC and NC+CE (p = 0.011 and 0.004, respectively); the highest specificity was reached by NC+CE+DWI (100%). Site-based analysis revealed highest detection rates for lymph node metastases for NC+DWI and NC, CE+DWI (73 and 76%, respectively); error rates were lower for NC, CE+DWI with 5% compared with 17% (NC+DWI). Detection rates for bone metastases were similarly high in NC+DWI and NC, CE+DWI (75 and 74%, respectively), while CE showed no benefit. For peritoneal metastases highest sensitivity was reached by NC+DWI (67%). Conclusion: The combination of NC+DWI showed better sensitivities than the combination of NC+CE. NC+DWI showed similar, sometimes even better sensitivities than NC+CE+DWI, but with lower specificities.

The assessment of left ventricular volume and function in gated small animal 18F-FDG PET/CT imaging: a comparative study of three commercially available software tools.

BACKGROUND: Several software tools have been developed for gated PET imaging that use distinct algorithms to analyze tracer uptake, myocardial perfusion, and left ventricle volumes and function. Studies suggest that different software tools cannot be used interchangeably in humans. In this study, we sought to compare the left ventricular parameters in gated 18F-FDG PET/CT imaging in mice by three commercially available software tools: PMOD, MIM, and QGS. METHODS AND RESULTS: Healthy mice underwent ECG-gated 18F-FDG imaging using a small-animal nanoPET/CT (Mediso) under isoflurane narcosis. Reconstructed gates PET images were subsequently analyzed in three different software tools, and cardiac volume and function (end-diastolic (EDV), end-systolic volumes (ESV), stroke volume (SV), and ejection fraction (EF)) were evaluated. While cardiac volumes correlated well between PMOD, MIM, and QGS, the left ventricular parameters and cardiac function differed in agreement using Bland-Altman analysis. EDV in PMOD vs. QGS: r = 0.85; p < 0.001, MIM vs. QGS: r = 0.92; p < 0.001, and MIM vs. PMOD: r = 0.88; p < 0.001, showed good correlations. Correlation was also found in ESV: PMOD vs. QGS: r = 0.48; p = 0.07, MIM vs QGS: r = 0.79; p < 0.001, and MIM vs. PMOD: r = 0.69; p < 0.01. SV showed good correlations in: PMOD vs. QGS: r = 0.73; p < 0.01, MIM vs. QGS: r = 0.86; p < 0.001, and MIM vs. PMOD: r = 0.92; p < 0.001. However, EF among correlated poorly: PMOD vs. QGS: r = -0.31; p = 0.26, MIM vs. QGS: r = 0.48; p = 0.07, and MIM vs. PMOD: r = 0.23; p = 0.41. Inter-class and intra-class correlation coefficient were > 0.9 underlining repeatability in using PMOD, MIM, and QGS for cardiac volume and function assessment. CONCLUSIONS: All three commercially available software tools are feasible in small animal cardiac volume assessment in gated 18F-FDG PET/CT imaging. However, due to software-related differences in agreement analysis for cardiac volumes and function, PMOD, MIM, and QGS cannot be used interchangeably in murine research.

Comparison of somatostatin receptor expression in patients with neuroendocrine tumours with and without somatostatin analogue treatment imaged with [18F]SiTATE.

Purpose: Somatostatin analogues (SSA) are frequently used in the treatment of neuroendocrine tumours. Recently, [18F]SiTATE entered the field of somatostatin receptor (SSR) positron emission tomography (PET)/computed tomography (CT) imaging. The purpose of this study was to compare the SSR-expression of differentiated gastroentero-pancreatic neuroendocrine tumours (GEP-NET) measured by [18F]SiTATE-PET/CT in patients with and without previous treatment with long-acting SSAs to evaluate if SSA treatment needs to be paused prior to [18F]SiTATE-PET/CT. Methods: 77 patients were examined with standardised [18F]SiTATE-PET/CT within clinical routine: 40 patients with long-acting SSAs up to 28 days prior to PET/CT examination and 37 patients without pre-treatment with SSAs. Maximum and mean standardized uptake values (SUVmax and SUVmean) of tumours and metastases (liver, lymphnode, mesenteric/peritoneal and bones) as well as representative background tissues (liver, spleen, adrenal gland, blood pool, small intestine, lung, bone) were measured, SUV ratios (SUVR) were calculated between tumours/metastases and liver, likewise between tumours/metastases and corresponding specific background, and compared between the two groups. Results: SUVmean of liver (5.4 ± 1.5 vs. 6.8 ± 1.8) and spleen (17.5 ± 6.8 vs. 36.7 ± 10.3) were significantly lower (p < 0.001) and SUVmean of blood pool (1.7 ± 0.6 vs. 1.3 ± 0.3) was significantly higher (p < 0.001) in patients with SSA pre-treatment compared to patients without. No significant differences between tumour-to-liver and specific tumour-to-background SUVRs were observed between both groups (all p > 0.05). Conclusion: In patients previously treated with SSAs, a significantly lower SSR expression ([18F]SiTATE uptake) in normal liver and spleen tissue was observed, as previously reported for 68Ga-labelled SSAs, without significant reduction of tumour-to-background contrast. Therefore, there is no evidence that SSA treatment needs to be paused prior to [18F]SiTATE-PET/CT.

Investigation of image-based lesion and kidney dosimetry protocols for 177Lu-PSMA-I&T therapy with and without a late SPECT/CT acquisition.

BACKGROUND: 177Lu-PSMA therapy has been successfully used to prolong the survival of patients with metastatic castration-resistant prostate cancer. Patient-specific dosimetry based on serial quantitative SPECT/CT imaging can support the understanding of dose-effect relationships. However, multiple SPECT/CT measurements can be challenging for patients, which motivates the investigation of efficient sampling schedules and their impact on dosimetry. In this study, different time samplings with respect to the number and timing of SPECT/CT acquisitions with and without a late measurement were investigated. MATERIALS AND METHODS: In total, 43 lesions and 10 kidneys of 5 patients receiving 177Lu-PSMA-I&T therapy were investigated. Whole-body SPECT/CT measurements were performed at 1, 2, 3 and 7 days post-injection. For both lesions (isocontour-based segmentation) and kidneys (CT-based segmentation), a reference model was employed including all four time points. To identify the best-matching fit function out of a pre-defined set of models, visual inspection, coefficients of variation and sum of squared errors were considered as goodness-of-fit criteria. Biologically effective doses (BEDs) calculated with different time samplings (days 1, 2, 3/1, 2, 7/1, 3, 7/2, 3, 7 and 1, 2/1, 3/1, 7) were compared to the reference. RESULTS: The best-fit function was found to be a mono-exponential model for lesions and a bi-exponential model with a population-based parameter and two free parameters for kidneys. The BEDs calculated with the time sampling 1, 3, 7 days showed the lowest deviations from the reference for lesions with 4 ± 5%. Without day 7, still 86% of all lesions showed deviations from the reference < 10%. The outlier deviations showed a positive correlation with the effective half-life of the respective lesions. For kidneys, including days 1, 2, 3 achieved the best results with 0 ± 1%. Generally, deviations for kidneys were found to be small for all time samplings (max. 13%). CONCLUSIONS: For combined optimization of the SPECT/CT time sampling for kidney and lesion dosimetry during 177Lu-PSMA-I&T therapy, the sampling with days 1, 3, 7 showed the smallest deviation from the reference. Without a late acquisition, using the schedule with days 1, 2, 3 is likewise feasible.

Biodistribution and dosimetry for combined [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T therapy using multi-isotope quantitative SPECT imaging.

PURPOSE: Quantitative SPECT for patient-specific dosimetry is a valuable tool in the scope of radionuclide therapy, although its clinical application for 225Ac-based treatments may be limited due to low therapeutic activities. Therefore, the aim of this study was to demonstrate the feasibility of clinical quantitative low-count SPECT imaging during [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T treatment. METHODS: Eight prostate cancer patients (1000 MBq/8 MBq [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T) received a single-bed quantitative 177Lu/225Ac SPECT/CT acquisition (1 h) at 24 h post treatment (high-energy collimator, 16 projections p. head à 3.5 min, 128 × 128 pixel). The gamma peak at 440 keV (width: 10%) of the progeny 213Bi was imaged along with the peak at 208 keV (width: 15%) of 177Lu. Quantification included CT-based attenuation and window-based scatter correction plus resolution modelling. Gaussian post-filtering with a full-width-half-maximum of 30 mm and 40-45 mm was employed to match the signal-to-noise ratio of 225Ac and 177Lu, respectively. RESULTS: Kidney (r = 0.96, p < 0.01) and lesion (r = 0.94, p < 0.01) SUV for [177Lu]Lu-PSMA-I&T and [225Ac]Ac-PSMA-I&T showed a strong and significant correlation. Kidney SUV were significantly higher (p < 0.01) for [225Ac]Ac-PSMA-I&T (2.5 ± 0.8 vs. 2.1 ± 0.9), while for [177Lu]Lu-PSMA-I&T lesion SUV were significantly higher (p = 0.03; 1.8 ± 1.1 vs. 2.1 ± 1.5). For absorbed dose estimates, significant differences regarding the kidneys remained, while no significant differences for lesion dosimetry were found. CONCLUSION: Quantitative low-count SPECT imaging of the peak at 440 keV during [225Ac]Ac-PSMA-I&T therapy is feasible. Multi-isotope imaging for [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T therapy indicates accumulation of free 213Bi in the kidneys.

Detection of apoptosis by [18F]ML-10 after cardiac ischemia-reperfusion injury in mice.

OBJECTIVE: Myocardial infarction leads to ischemic heart disease and cell death, which is still a major obstacle in western society. In vivo imaging of apoptosis, a defined cascade of cell death, could identify myocardial tissue at risk. METHODS: Using 2-(5-[18F]fluoropentyl)-2-methyl-malonic acid ([18F]ML-10) in autoradiography and positron emission tomography (PET) visualized apoptosis in a mouse model of transient ligation of the left anterior descending (LAD) artery. 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET imaging indicated the defect area. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) histology stain indicated cardiac apoptosis. RESULTS: [18F]ML-10 uptake was evident in the ischemic area after transient LAD ligation in ex vivo autoradiography and in vivo PET imaging. Detection of [18F]ML-10 is in line with the defect visualized by [18F]FDG and the histological approach of TUNEL staining. CONCLUSION: The tracer [18F]ML-10 is suitable for detecting apoptosis after transient LAD ligation in mice.

Total Tumor Volume on 18F-PSMA-1007 PET as Additional Imaging Biomarker in mCRPC Patients Undergoing PSMA-Targeted Alpha Therapy with 225Ac-PSMA-I&T.

Background: PSMA-based alpha therapy using 225Ac-PSMA-I&T provides treatment for metastatic castration-resistant prostate cancer (mCRPC), even after the failure of 177Lu-PSMA radioligand therapy (RLT). In clinical routine, the total tumor volume (TTV) on PSMA PET impacts therapy outcomes and plays an increasing role in mCRPC patients. Hence, we aimed to assess TTV and its changes during 225Ac-PSMA-I&T RLT. Methods: mCRPC patients undergoing RLT with 225Ac-PSMA-I&T with available 18F-PSMA-1007 PET/CT prior to therapy initiation were included. TTV was assessed in all patients using established cut-off values. Image derived, clinical and biochemistry parameters (PSA, LDH, AP, pain score) were analyzed prior to and after two cycles of 225Ac-PSMA. Changes in TTV and further parameters were directly compared and then correlated with established response criteria, such as RECIST 1.1 or mPERCIST. Results: 13 mCRPC patients were included. The median overall survival (OS) was 10 months. Prior to 225Ac-PSMA RLT, there was no significant correlation between TTV with other clinical parameters (p > 0.05 each). Between short-term survivors (STS, <10 months OS) and long-term survivors (LTS, ≥10 months OS), TTV and PSA were comparable (p = 0.592 & p = 0.286, respectively), whereas AP was significantly lower in the LTS (p = 0.029). A total of 7/13 patients completed two cycles and underwent a follow-up 18F-PSMA-1007 PET/CT. Among these patients, there was a significant decrease in TTV (median 835 vs. 201 mL, p = 0.028) and PSA (median 687 ng/dL vs. 178 ng/dL, p = 0.018) after two cycles of 225Ac-PSMA RLT. Here, percentage changes of TTV after two cycles showed no direct correlation to all other clinical parameters (p > 0.05 each). In two patients, new PET-avid lesions were detected on 18F-PSMA-1007 PET/CT. However, TTV and PSA were decreasing or stable. Conclusion: PET-derived assessment of TTV is an easily applicable imaging biomarker independent of other established parameters prior to 225Ac-PSMA RLT in these preliminary follow-up data. Even after the failure of 177Lu-PSMA, patients with extensive TTV seem to profit from RLT. All but one patient who was eligible for ≥2 cycles of 225Ac-PSMA-RLT demonstrated drastic TTV decreases without direct correlation to other biomarkers, such as serum PSA changes. Changes in TTV might hence improve the response assessment compared to standard classifiers by reflecting the current tumor load independent of the occurrence of new lesions.

Comparison of transient and permanent LAD ligation in mice using 18F-FDG PET imaging.

OBJECTIVE: Animal models for myocardial injuries represent important cornerstones in cardiovascular research to monitor the pathological processes and therapeutic approaches. We investigated the association of 18F-FDG derived left ventricular metabolic volume (LVMV), defect area and cardiac function in mice after permanent or transient ligation of the left anterior descending artery (LAD). METHODS: Serial non-invasive ECG-gated 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (18F-FDG PET) after permanent or transient LAD ligation enabled a longitudinal in vivo correlation of 18F-FDG derived left ventricular metabolic volume to functional parameters and myocardial defect. RESULTS: The LVMV shows a more prominent drop after permanent than transient LAD ligation and recovers after 30 days. The loss of LVMV correlates with the defect area assessed by QPS software. Cardiac function parameters (e.g., EDV, ESV, SV) by the QGS software positively correlate with LVMV after permanent and transient LAD ligation. CONCLUSIONS: This study provides novel insight into 18F-FDG derived LVMV after permanent and transient LAD ligation by longitudinal in 18F-FDG PET imaging and underlines the associations of the FDG derived parameter and cardiac function.

Detection of cardiac apoptosis by [18F]ML-10 in a mouse model of permanent LAD ligation.

PURPOSE: The loss of viable cardiac cells and cell death by myocardial infarction (MI) is still a significant obstacle in preventing deteriorating heart failure. Imaging of apoptosis, a defined cascade to cell death, could identify areas at risk. PROCEDURES: Using 2-(5-[18F]fluoropentyl)-2-methyl-malonic acid ([18F]ML-10) in autoradiography and positron emission tomography (PET) visualized apoptosis in murine hearts after permanent ligation of the left anterior descending artery (LAD) inducing myocardial infarction (MI). 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET imaging localized the infarct area after MI. Histology by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining validated apoptosis in the heart. RESULTS: Accumulation of [18F]ML-10 was evident in the infarct area after permanent ligation of the LAD in autoradiography and PET imaging. Detection of apoptosis by [18F]ML-10 is in line with the defect visualized by [18F]FDG and the histological approach. CONCLUSION: [18F]ML-10 could be a suitable tracer for apoptosis imaging in a mouse model of permanent LAD ligation.

Outcome after PSMA-PET/CT-based salvage radiotherapy for nodal recurrence after radical prostatectomy.

PURPOSE: Nodal recurrent prostate cancer (PCa) represents a common state of disease, amenable to local therapy. PSMA-PET/CT detects PCa recurrence at low PSA levels. The aim of this study was to evaluate the outcome of PSMA-PET/CT-based salvage radiotherapy (sRT) for lymph node (LN) recurrence. METHODS: A total of 100 consecutive patients treated with PSMA-PET/CT-based salvage elective nodal radiotherapy (sENRT) for LN recurrence were retrospectively examined. Patients underwent PSMA-PET/CT scan due to biochemical persistence (bcP, 76%) or biochemical recurrence (bcR, 24%) after radical prostatectomy (RP). Biochemical recurrence-free survival (BRFS) defined as PSA < post-RT nadir + 0.2 ng/ml and distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method and uni- and multivariate analysis was performed. RESULTS: Median follow-up was 37 months. Median PSA at PSMA-PET/CT was 1.7 ng/ml (range 0.1-40.1) in patients with bcP and 1.4 ng/ml (range 0.3-5.1) in patients with bcR. PSMA-PET/CT detected 1, 2, and 3 or more LN metastases in 35%, 23%, and 42%, respectively. Eighty-three percent had only pelvic, 2% had only paraaortic, and 15% had pelvic and paraaortic LN metastases. Cumulatively, a total dose converted to EQD21.5 Gy of 66 Gy (60-70 Gy) was delivered to the prostatic fossa, 70 Gy (66-72 Gy) to the local recurrence, if present, 65.1 Gy (56-66 Gy) to PET-positive lymph nodes, and 47.5 Gy (42.4-50.9 Gy) to the lymphatic pathways. Concomitant androgen deprivation therapy (ADT) was administered in 83% of patients. One-, 2-, and 3-year BRFS was 80.7%, 71.6%, and 65.8%, respectively. One-, 2-, and 3-year DMFS was 91.6%, 79.1%, and 66.4%, respectively. In multivariate analysis, concomitant ADT, longer ADT duration (≥ 12 vs. < 12 months) and LN localization (pelvic vs. paraaortic) were associated with improved BRFS and concomitant ADT and lower PSA value before sRT (< 1 vs. > 1 ng/ml) with improved DMFS, respectively. No such association was seen for the number of affected lymph nodes. CONCLUSIONS: Overall, the present analysis shows that the so far, unmatched sensitivity and specificity of PSMA-PET/CT translates in comparably high BRFS and DMFS after PSMA-PET/CT-based sENRT for patients with PCa LN recurrence. Concomitant ADT, duration of ADT, PSA value before sRT, and localization of LN metastases were significant factors for improved outcome.

Quantitative myocardial perfusion SPECT/CT for the assessment of myocardial tracer uptake in patients with three-vessel coronary artery disease: Initial experiences and results.

BACKGROUND: To evaluate quantitative myocardial perfusion SPECT/CT datasets for routine clinical reporting and the assessment of myocardial tracer uptake in patients with severe TVCAD. METHODS: MPS scans were reconstructed as quantitative SPECT datasets using CTs from internal (SPECT/CT, Q_INT) and external (PET/CT, Q_EXT) sources for attenuation correction. TPD was calculated and compared to the TPD from non-quantitative SPECT datasets of the same patients. SUVmax, SUVpeak, and SUVmean were compared between Q_INT and Q_EXT SPECT datasets. Global SUVmax and SUVpeak were compared between patients with and without TVCAD. RESULTS: Quantitative reconstruction was feasible. TPD showed an excellent correlation between quantitative and non-quantitative SPECT datasets. SUVmax, SUVpeak, and SUVmean showed an excellent correlation between Q_INT and Q_EXT SPECT datasets, though mean SUVmean differed significantly between the two groups. Global SUVmax and SUVpeak were significantly reduced in patients with TVCAD. CONCLUSIONS: Absolute quantification of myocardial tracer uptake is feasible. The method seems to be robust and principally suitable for routine clinical reporting. Quantitative SPECT might become a valuable tool for the assessment of severe coronary artery disease in a setting of balanced ischemia, where potentially life-threatening conditions might otherwise go undetected.

Patient-Reported and Oncological Outcomes of Salvage Therapies for PSMA-Positive Nodal Recurrent Prostate Cancer: Real-Life Experiences and Implications for Future Trial Design.

INTRODUCTION: The role of salvage lymph node dissection (SLND) and radiotherapy (SLNRT) in the management of nodal-only recurrent prostate cancer (PC) remains controversial. In addition, impact on health-related quality of life (HRQOL) has not been adequately evaluated yet. MATERIALS AND METHODS: Analysis was limited to patients that were diagnosed with nodal-only recurrent PC via PSMA-PET/CT. SLND was performed via open approach. For SLNRT, dose regimens were normo- or slightly hypo-fractionated with a simultaneous boost to the PET-positive recurrences. EORTC QLQ-C30 and PR-25 questionnaires were used to assess HRQOL. Continence status was assessed using daily pad usage and the validated ICIQ-SF questionnaire. For multivariable analysis, Cox regression models were used (p<0.05). RESULTS: 138 patients (SLND: 71; SLNRT: 67) were included in the retrospective analysis. Median follow-up was 47 months (mo) for SLNRT patients (IQR 40-61), and 33mo for SLND patients (IQR 20-49; p<0.001). In total, 61 patients (91.0%) in the SLNRT cohort and 43 patients (65.2%; p<0.001) in the SLND cohort underwent ADT anytime during the follow-up period. In multivariate Cox regression analysis, SLNRT could be confirmed as an independent predictor for increased PSA progression-free survival (PFS; HR 0.08, 95%CI 0.040 - 0.142, p<0.001). Estimated median metastasis-free survival (MFS) was 70mo for the total cohort without statistically significant differences between both subgroups (p=0.216). There were no significant differences regarding general HRQOL, daily pad usage, and ICIQ-SF scores between the respective cohorts. CONCLUSIONS: In a large contemporary series of patients with nodal-only recurrent PC based on PSMA-PET/CT staging, we observed significantly increased PSA PFS in patients undergoing SLNRT while no significant differences could be observed in MFS, and functional outcomes including HRQOL.

Feasibility of Different Tumor Delineation Approaches for 18F-PSMA-1007 PET/CT Imaging in Prostate Cancer Patients.

BACKGROUND: Delineation of PSMA-positive tumor volume on PET using PSMA-ligands is of highest clinical interest as changes of PSMA-PET/CT-derived whole tumor volume (WTV) have shown to correlate with treatment response in metastatic prostate cancer patients. So far, WTV estimation was performed on PET using 68Ga-labeled ligands; nonetheless, 18F-labeled PET ligands are gaining increasing importance due to advantages over 68Ga-labeled compounds. However, standardized tumor delineation methods for 18F-labeled PET ligands have not been established so far. As correlation of PET-based information and morphological extent in osseous and visceral metastases is hampered by morphological delineation, low contrast in liver tissue and movement artefacts, we correlated CT-based volume of lymph node metastases (LNM) and different PET-based delineation approaches for thresholding on 18F-PSMA-1007 PET. METHODS: Fifty patients with metastatic prostate cancer, 18F-PSMA-1007 PET/CT and non-bulky LNM (short-axis diameter ≥10mm) were included. Fifty LNM were volumetrically assessed on contrast-enhanced CT (volumetric reference standard). Different approaches for tumor volume delineation were applied and correlated with the reference standard: I) fixed SUV threshold, II) isocontour thresholding relative to SUVmax (SUV%), and thresholds relative to III) liver (SUVliver), IV) parotis (SUVparotis) and V) spleen (SUVspleen). RESULTS: A fixed SUV of 4.0 (r=0.807, r2 = 0.651, p<0.001) showed the best overall association with the volumetric reference. 55% SUVmax (r=0.627, r2 = 0.393, p<0.001) showed highest association using an isocontour-based threshold. Best background-based approaches were 60% SUVliver (r=0.715, r2 = 0.511, p<0.001), 80% SUVparotis (r=0.762, r2 = 0.581, p<0.001) and 60% SUVspleen (r=0.645, r2 = 0.416, p<0.001). Background tissues SUVliver, SUVparotis & SUVspleen did not correlate (p>0.05 each). Recently reported cut-offs for intraprostatic tumor delineation (isocontour 44% SUVmax, 42% SUVmax and 20% SUVmax) revealed inferior association for LNM delineation. CONCLUSIONS: A threshold of SUV 4.0 for tumor delineation showed highest association with volumetric reference standard irrespective of potential changes in PSMA-avidity of background tissues (e. g. parotis). This approach is easily applicable in clinical routine without specific software requirements. Further studies applying this approach for total tumor volume delineation are initiated.

Cardiac 18F-FDG Positron Emission Tomography: An Accurate Tool to Monitor In vivo Metabolic and Functional Alterations in Murine Myocardial Infarction.

Cardiac monitoring after murine myocardial infarction, using serial non-invasive cardiac 18F-FDG positron emissions tomography (PET) represents a suitable and accurate tool for in vivo studies. Cardiac PET imaging enables tracking metabolic alterations, heart function parameters and provides correlations of the infarct size to histology. ECG-gated 18F-FDG PET scans using a dedicated small-animal PET scanner were performed in mice at baseline, 3, 14, and 30 days after myocardial infarct (MI) by permanent ligation of the left anterior descending (LAD) artery. The percentage of the injected dose per gram (%ID/g) in the heart, left ventricular metabolic volume (LVMV), myocardial defect, and left ventricular function parameters: end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and the ejection fraction (EF%) were estimated. PET assessment of the defect positively correlates with post-infarct histology at 3 and 30 days. Infarcted murine hearts show an immediate decrease in LVMV and an increase in %ID/g early after infarction, diminishing in the remodeling process. This study of serial cardiac PET scans provides insight for murine myocardial infarction models by novel infarct surrogate parameters. It depicts that serial PET imaging is a valid, accurate, and multimodal non-invasive assessment.

Correlation of an Index-Lesion-Based SPECT Dosimetry Method with Mean Tumor Dose and Clinical Outcome after 177Lu-PSMA-617 Radioligand Therapy.

BACKGROUND: Dosimetry can tailor prostate-specific membrane-antigen-targeted radioligand therapy (PSMA-RLT) for metastatic castration-resistant prostate cancer (mCRPC). However, whole-body tumor dosimetry is challenging in patients with a high tumor burden. We evaluate a simplified index-lesion-based single-photon emission computed tomography (SPECT) dosimetry method in correlation with clinical outcome. METHODS: 30 mCRPC patients were included (median 71 years). The dosimetry was performed for the first cycle using quantitative 177Lu-SPECT. The response was evaluated using RECIST 1.1 and PERCIST criteria, as well as changes in PSMA-positive tumor volume (PSMA-TV) in post-therapy PSMA-PET and biochemical response according to PSA changes after two RLT cycles. RESULTS: Mean tumor doses as well as index-lesion doses were significantly higher in PERCIST responders compared to non-responders (10.2 ± 12.0 Gy/GBq vs. 4.0 ± 2.9 Gy/GBq, p = 0.03 and 13.7 ± 14.2 Gy/GBq vs. 5.9 ± 4.4 Gy/GBq, p = 0.04, respectively). No significant differences in mean tumor and index lesion doses were observed between responders and non-responders according to RECIST 1.1, PSMA-TV, and biochemical response criteria. CONCLUSION: Compared to mean tumor doses on a patient level, single index-lesion-based SPECT dosimetry correlates equally well with the response to PSMA-RLT according to PERCIST criteria and may represent a fast and feasible dosimetry approach for clinical routine.

Comparison of metabolic and functional parameters using cardiac 18F-FDG-PET in early to mid-adulthood male and female mice.

BACKGROUND: In this descriptive study of male and female mice at different weeks of age, we use serial non-invasive cardiac 18F-FDG-PET scans to follow up on metabolic alterations, heart function parameters, and the ECG of both sexes in early to mid-adulthood. METHODS: ECG-gated 18F-FDG-PET scans were performed in mice on 10, 14, and 18 weeks of age, using a dedicated small-animal PET scanner. The percentage of the injected activity per gram (%IA/g) in the heart, left ventricular metabolic volume (LVMV), myocardial viability and left ventricular function parameters: end-diastolic (EDV), end-systolic (ESV), stroke volume (SV), and the ejection fraction (EF%) were estimated. RESULTS: Compared to their age-matched female counterpart, male mice showed a constant increase in LVMV and ventricular volume during the follow-up. In contrast, female mice remain stable after ten weeks of age. Furthermore, male mice showed lower heart rates, positive correlation with cardiac %IA/g, and negative correlation with LVMV. CONCLUSION: In this study of serial cardiac PET scans, we provide insight for basic murine research models, showing that mice gender and age show distinct cardiac metabolisms. These physiologic alterations need to be considered when planning in vivo injury models to avoid potential pitfalls.