Evaluation of the 177mLu-concentration in in-house produced 177Lu-radiopharmaceuticals and commercially available Lutathera®.

BACKGROUND: 177Lu-radiopharmaceuticals can contain the metastable impurity [177mLu]lutetium with a physical half-life of 160.4 days, in varying concentrations depending on the route of production of the radionuclidic precursor [177Lu]lutetium. Due to the long half-life of [177mLu]lutetium, difficulties with waste disposal or sterility testing could arise. Here, we analyzed several 177Lu-samples of different origins and suppliers regarding their 177mLu-concentration. RESULTS: All samples tested showed a 177mLu-concentration in the range that was stated on the certificate of analysis from the supplier which is in accordance with the European Pharmacopoeia. CONCLUSIONS: Although all 177mLu-concentrations were in accordance with the European Pharmacopoeia, we need to take into account the respective national legislation regarding radioactivity release limits. With regard to the German legislation, several probes for sterility testing in external laboratories could not be released for transport due to the concentration of [177mLu]lutetium. Moreover, waste water tanks should specifically be monitored for 177mLu-concentration, when e.g. Lutathera® is administered in the clinic.

[177Lu]Lu-PSMA Therapy as an Individual Treatment Approach for Patients with High-Grade Glioma: Dosimetry Results and Critical Statement.

The theranostic use of prostate-specific membrane antigen (PSMA) appears to be promising in patients with high-grade glioma. This study investigated [177Lu]Lu-PSMA therapy as an individual treatment approach with a focus on intratherapeutic dosimetry. Methods: Three patients were treated with a median of 6.03 GBq (interquartile range [IQR], 5.74-6.10) of [177Lu]Lu-PSMA. Intratherapeutic dosimetry was performed using a hybrid scenario with planar whole-body scintigraphy at 2, 24, and 48 h after treatment injection and SPECT/CT at 48 h after injection. Additive whole-body scintigraphy at 8 d after injection was performed on 1 patient. Results: The median doses were 0.56 Gy (IQR, 0.36-1.25 Gy) to tumor, 0.27 Gy (IQR, 0.16-0.57 Gy) to risk organs, 2.13 Gy (IQR, 1.55-2.89 Gy) to kidneys, and 0.76 Gy (IQR, 0.70-1.20 Gy) to salivary glands. Whole-body exposure was 0.11 Gy (IQR, 0.06-0.18 Gy). Conclusion: Because the intratherapeutic tumor dose is lower than that used in external radiation oncology, the effectiveness of treatment is questionable.

Same same but different: dopamine transporter SPECT on scanners with CZT vs. NaI detectors.

BACKGROUND: The aims of this study were to establish a normal database (NDB) for semiquantification of dopamine transporter (DAT) single-photon emission computed tomography (SPECT) with [123I]FP-CIT on a cadmium zinc telluride (CZT) camera, test the preexisting NaI-derived NDB for use in CZT scans, and compare the diagnostic findings in subjects imaged with a CZT scanner with either the preexisting NaI-based NDB or our newly defined CZT NDB. METHODS: The sample comprised 73 subjects with clinically uncertain parkinsonian syndrome (PS) who prospectively underwent [123I]FP-CIT SPECT on a CZT camera according to standard guidelines with identical acquisition and reconstruction protocols (DaTQUANT). Two experienced readers visually assessed the images and binarized the subjects into "non-neurodegenerative PS" and "neurodegenerative PS". Twenty-five subjects from the "non-neurodegenerative PS" subgroup were randomly selected to establish a CZT NDB. The remaining 48 subjects were defined as "test group". DaTQUANT was used to determine the specific binding ratio (SBR). For the test group, SBR values were transformed to z-scores for the putamen utilizing both the CZT NDB and the manufacturer-provided NaI-based NDB (GE NDB). A predefined fixed cut-off of -2 was used for dichotomization of z-scores to classify neurodegenerative and non-neurodegenerative PS. Performance of semiquantification using the two NDB to identify subjects with neurodegenerative PS was assessed in comparison with the visual rating. Furthermore, a randomized head-to-head comparison of both detector systems was performed semiquantitatively in a subset of 32 out of all 73 subjects. RESULTS: Compared to the visual rating as reference, semiquantification based on the dedicated CZT NDB led to fewer discordant ratings than the GE NDB in CZT scans (3 vs. 8 out of 48 subjects). This can be attributed to the putaminal z-scores being consistently higher with the GE NDB on a CZT camera (median absolute difference of 1.68), suggesting an optimal cut-off of -0.5 for the GE NDB instead of -2.0. Average binding ratios and z-scores were significantly lower in CZT compared to NaI data. CONCLUSIONS: Use of a dedicated, CZT-derived NDB is recommended in [123I]FP-CIT SPECT with a CZT camera since it improves agreement between semiquantification and visual assessment.

Selective Internal Radiation Therapy in Breast Cancer Liver Metastases: Outcome Assessment Applying a Prognostic Score.

Selective internal radiation therapy (SIRT) is a therapy option in patients with breast cancer liver metastasis (BCLM). This analysis aimed at identifying a prognostic score regarding overall survival (OS) after SIRT using routine pretherapeutic parameters. Retrospective analysis of 38 patients (age, 59 (39-84) years) with BCLM and 42 SIRT procedures. Cox regression for OS included clinical factors (age, ECOG and prior treatments), laboratory parameters, hepatic tumor load and dose reduction due to hepatopulmonary shunt. Elevated baseline ALT and/or AST was present if CTCAE grade ≥ 2 was fulfilled (>3 times the upper limit of normal). Median OS after SIRT was 6.4 months. In univariable Cox, ECOG ≥ 1 (hazard ratio (HR), 3.8), presence of elevated baseline ALT/AST (HR, 3.8), prior liver surgery (HR, 10.2), and dose reduction of 40% (HR, 8.1) predicted shorter OS (each p < 0.05). Multivariable Cox confirmed ECOG ≥ 1 (HR, 2.34; p = 0.012) and elevated baseline ALT/AST (HR, 4.16; p < 0.001). Combining both factors, median OS decreased from 19.2 months (0 risk factors; n = 14 procedures) to 5.9 months (1 factor; n = 20) or 2.2 months (2 factors; n = 8; p < 0.001). The proposed score may facilitate pretherapeutic identification of patients with unfavorable OS after SIRT. This may help to balance potential life prolongation with the hazards of invasive treatment and hospitalization.

Optimization of SPECT/CT imaging protocols for quantitative and qualitative 99mTc SPECT.

BACKGROUND: The introduction of hybrid SPECT/CT devices enables quantitative imaging in SPECT, providing a methodological setup for quantitation using SPECT tracers comparable to PET/CT. We evaluated a specific quantitative reconstruction algorithm for SPECT data using a 99mTc-filled NEMA phantom. Quantitative and qualitative image parameters were evaluated for different parametrizations of the acquisition and reconstruction protocol to identify an optimized quantitative protocol. RESULTS: The reconstructed activity concentration (ACrec) and the signal-to-noise ratio (SNR) of all examined protocols (n = 16) were significantly affected by the parametrization of the weighting factor k used in scatter correction, the total number of iterations and the sphere volume (all, p < 0.0001). The two examined SPECT acquisition protocols (with 60 or 120 projections) had a minor impact on the ACrec and no significant impact on the SNR. In comparison to the known AC, the use of default scatter correction (k = 0.47) or object-specific scatter correction (k = 0.18) resulted in an underestimation of ACrec in the largest sphere volume (26.5 ml) by - 13.9 kBq/ml (- 16.3%) and - 7.1 kBq/ml (- 8.4%), respectively. An increase in total iterations leads to an increase in estimated AC and a decrease in SNR. The mean difference between ACrec and known AC decreased with an increasing number of total iterations (e.g., for 20 iterations (2 iterations/10 subsets) = - 14.6 kBq/ml (- 17.1%), 240 iterations (24i/10s) = - 8.0 kBq/ml (- 9.4%), p < 0.0001). In parallel, the mean SNR decreased significantly from 2i/10s to 24i/10s by 76% (p < 0.0001). CONCLUSION: Quantitative SPECT imaging is feasible with the used reconstruction algorithm and hybrid SPECT/CT, and its consistent implementation in diagnostics may provide perspectives for quantification in routine clinical practice (e.g., assessment of bone metabolism). When combining quantitative analysis and diagnostic imaging, we recommend using two different reconstruction protocols with task-specific optimized setups (quantitative vs. qualitative reconstruction). Furthermore, individual scatter correction significantly improves both quantitative and qualitative results.

An optimized imaging protocol for [99mTc]Tc-DPD scintigraphy and SPECT/CT quantification in cardiac transthyretin (ATTR) amyloidosis.

BACKGROUND: In [99mTc]Tc-DPD scintigraphy for myocardial ATTR amyloidosis, planar images 3 hour p.i. and SPECT/CT acquisition in L-mode are recommended. This study investigated if earlier planar images (1 hour p.i.) are beneficial and if SPECT/CT acquisition should be preferred in H-mode (180° detector angle) or L-mode (90°). METHODS: In SPECT/CT phantom measurements (NaI cameras, N = 2; CZT, N = 1), peak contrast recovery (CRpeak) was derived from sphere inserts or myocardial insert (cardiac phantom; signal-to-background ratio [SBR], 10:1 or 5:1). In 25 positive and 38 negative patients (reference: endomyocardial biopsy or clinical diagnosis), Perugini scores and heart-to-contralateral (H/CL) count ratios were derived from planar images 1 hour and 3 hour p.i. RESULTS: In phantom measurements, accuracy of myocardial CRpeak at SBR 10:1 (H-mode, 0.95-0.99) and reproducibility at 5:1 (H-mode, 1.02-1.14) was comparable for H-mode and L-mode. However, L-mode showed higher variability of background counts and sphere CRpeak throughout the field of view than H-mode. In patients, sensitivity/specificity were ≥ 95% for H/CL ratios at both time points and visual scoring 3 hour. At 1 hour, visual scores showed specificity of 89% and reduced reader's confidence. CONCLUSIONS: Early DPD images provided no additional value for visual scoring or H/CL ratios. In SPECT/CT, H-mode is preferred over L-mode, especially if quantification is applied apart from the myocardium.

FDG-PET/CT for pretherapeutic lymph node staging in non-small cell lung cancer: A tailored approach to the ESTS/ESMO guideline workflow.

OBJECTIVES: In patients with NSCLC, current ESTS and ESMO guidelines recommend invasive lymph node (LN) staging with EBUS-TBNA even if FDG-PET/CT is negative for mediastinal LNs if at least one of three risk factors is present (cN1, non-peripheral primary or primary >3 cm). Modified workflows to avoid unnecessary invasive procedures were evaluated. MATERIALS AND METHODS: Monocentric retrospective analysis of pretherapeutic FDG-PET/CT in 247 patients with NSCLC (62 % male; age, 68 [43-88] years) using an analog or digital PET/CT scanner. PET windowing was standardized. LNs were positive if 'LN uptake > mediastinal blood pool' or short axis >10 mm. Surgery or EBUS-TBNA served as reference for diagnostic accuracy per LN station. In all patients with negative mediastinal LNs by PET/CT, LN histology from surgery was available. RESULTS: Among 700 L N stations analyzed, 180 were malignant. Sensitivity and specificity of PET/CT per LN station were 93 % and 71 %. Following current guidelines, 76 patients with mediastinal negative PET/CT required confirmatory invasive staging. Only 5/76 patients had unexpected pN2 (all had adenocarcinoma). In a modified approach, confirmatory invasive staging was confined to patients with mediastinal negative PET/CT who showed all three risk factors. Using this modification, EBUS-TBNA could have been omitted in 62 (82 %) of the 76 patients who required EBUS-TBNA based on current recommendation. Among these 62 patients, only one patient had unsuspected pN2 (single-level) while the remaining 61 of 62 omitted EBUS-TBNA were deemed unnecessary because mediastinal LNs were confirmed to be negative. No multi-level pN2 would have been missed. CONCLUSION: In the current analysis, 82 % of EBUS-TBNA procedures in patients with mediastinal negative PET/CT could have been omitted by modifying the current guideline workflow as proposed (i.e., restricting EBUS-TBNA in patients with cN0/1 to those with all three risk factors). This was consistent with different PET/CT scanners. Prospective confirmation is required.

Asphericity of tumor FDG uptake in non-small cell lung cancer: reproducibility and implications for harmonization in multicenter studies.

BACKGROUND: Asphericity (ASP) of the primary tumor's metabolic tumor volume (MTV) in FDG-PET/CT is independently predictive for survival in patients with non-small cell lung cancer (NSCLC). However, comparability between PET systems may be limited. Therefore, reproducibility of ASP was evaluated at varying image reconstruction and acquisition times to assess feasibility of ASP assessment in multicenter studies. METHODS: This is a retrospective study of 50 patients with NSCLC (female 20; median age 69 years) undergoing pretherapeutic FDG-PET/CT (median 3.7 MBq/kg; 180 s/bed position). Reconstruction used OSEM with TOF4/16 (iterations 4; subsets 16; in-plane filter 2.0, 6.4 or 9.5 mm), TOF4/8 (4 it; 8 ss; filter 2.0/6.0/9.5 mm), PSF + TOF2/17 (2 it; 17 ss; filter 2.0/7.0/10.0 mm) or Bayesian-penalized likelihood (Q.Clear; beta, 600/1750/4000). Resulting reconstructed spatial resolution (FWHM) was determined from hot sphere inserts of a NEMA IEC phantom. Data with approx. 5-mm FWHM were retrospectively smoothed to achieve 7-mm FWHM. List mode data were rebinned for acquisition times of 120/90/60 s. Threshold-based delineation of primary tumor MTV was followed by evaluation of relative ASP/SUVmax/MTV differences between datasets and resulting proportions of discordantly classified cases. RESULTS: Reconstructed resolution for narrow/medium/wide in-plane filter (or low/medium/high beta) was approx. 5/7/9 mm FWHM. Comparing different pairs of reconstructed resolution between TOF4/8, PSF + TOF2/17, Q.Clear and the reference algorithm TOF4/16, ASP differences was lowest at FWHM of 7 versus 7 mm. Proportions of discordant cases (ASP > 19.5% vs. ≤ 19.5%) were also lowest at 7 mm (TOF4/8, 2%; PSF + TOF2/17, 4%; Q.Clear, 10%). Smoothing of 5-mm data to 7-mm FWHM significantly reduced discordant cases (TOF4/8, 38% reduced to 2%; PSF + TOF2/17, 12% to 4%; Q.Clear, 10% to 6%), resulting in proportions comparable to original 7-mm data. Shorter acquisition time only increased proportions of discordant cases at < 90 s. CONCLUSIONS: ASP differences were mainly determined by reconstructed spatial resolution, and multicenter studies should aim at comparable FWHM (e.g., 7 mm; determined by in-plane filter width). This reduces discordant cases (high vs. low ASP) to an acceptable proportion for TOF and PSF + TOF of < 5% (Q.Clear: 10%). Data with better resolution (i.e., lower FWHM) could be retrospectively smoothed to the desired FWHM, resulting in a comparable number of discordant cases.

Reconstructed spatial resolution and contrast recovery with Bayesian penalized likelihood reconstruction (Q.Clear) for FDG-PET compared to time-of-flight (TOF) with point spread function (PSF).

BACKGROUND: Bayesian penalized likelihood reconstruction for PET (e.g., GE Q.Clear) aims at improving convergence of lesion activity while ensuring sufficient signal-to-noise ratio (SNR). This study evaluated reconstructed spatial resolution, maximum/peak contrast recovery (CRmax/CRpeak) and SNR of Q.Clear compared to time-of-flight (TOF) OSEM with and without point spread function (PSF) modeling. METHODS: The NEMA IEC Body phantom was scanned five times (3 min scan duration, 30 min between scans, background, 1.5-3.9 kBq/ml F18) with a GE Discovery MI PET/CT (3-ring detector) with spheres filled with 8-, 4-, or 2-fold the background activity concentration (SBR 8:1, 4:1, 2:1). Reconstruction included Q.Clear (beta, 150/300/450), "PSF+TOF4/16" (iterations, 4; subsets, 16; in-plane filter, 2.0 mm), "OSEM+TOF4/16" (identical parameters), "PSF+TOF2/17" (2 it, 17 ss, 2.0 mm filter), "OSEM+TOF2/17" (identical), "PSF+TOF4/8" (4 it, 8 ss, 6.4 mm), and "OSEM+TOF2/8" (2 it, 8 ss, 6.4 mm). Spatial resolution was derived from 3D sphere activity profiles. RC as (sphere activity concentration [AC]/true AC). SNR as (background mean AC/background AC standard deviation). RESULTS: Spatial resolution of Q.Clear150 was significantly better than all conventional algorithms at SBR 8:1 and 4:1 (Wilcoxon, each p < 0.05). At SBR 4:1 and 2:1, the spatial resolution of Q.Clear300/450 was similar or inferior to PSF+TOF4/16 and OSEM+TOF4/16. Small sphere CRpeak generally underestimated true AC, and it was similar for Q.Clear150/300/450 as with PSF+TOF4/16 or PSF+TOF2/17 (i.e., relative differences < 10%). Q.Clear provided similar or higher CRpeak as OSEM+TOF4/16 and OSEM+TOF2/17 resulting in a consistently better tradeoff between CRpeak and SNR with Q.Clear. Compared to PSF+TOF4/8/OSEM+TOF2/8, Q.Clear150/300/450 showed lower SNR but higher CRpeak. CONCLUSIONS: Q.Clear consistently improved reconstructed spatial resolution at high and medium SBR compared to PSF+TOF and OSEM+TOF, but only with beta = 150. However, this is at the cost of inferior SNR with Q.Clear150 compared to Q.Clear300/450 and PSF+TOF4/16/PSF+TOF2/17 while CRpeak for the small spheres did not improve considerably. This suggests that Q.Clear300/450 may be advantageous for the 3-ring detector configuration because the tradeoff between CR and SNR with Q.Clear300/450 was superior to PSF+TOF4/16, OSEM+TOF4/16, and OSEM+TOF2/17. However, it requires validation by systematic evaluation in patients at different activity and acquisition protocols.