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OBJECTIVES: PET-based radiomic metrics are increasingly utilized as predictive image biomarkers. However, the repeatability of radiomic features on PET has not been assessed in a test-retest setting. The prostate-specific membrane antigen-targeted compound 18 F-DCFPyL is a high-affinity, high-contrast PET agent that we utilized in a test-retest cohort of men with metastatic prostate cancer (PC). METHODS: Data of 21 patients enrolled in a prospective clinical trial with histologically proven PC underwent two 18 F-DCFPyL PET scans within 7 days, using identical acquisition and reconstruction parameters. Sites of disease were segmented and a set of 29 different radiomic parameters were assessed on both scans. We determined repeatability of quantification by using Pearson's correlations, within-subject coefficient of variation (wCOV), and Bland-Altman analysis. RESULTS: In total, 230 lesions (177 bone, 38 lymph nodes, 15 others) were assessed on both scans. For all investigated radiomic features, a broad range of inter-scan correlation was found (r, 0.07-0.95), with acceptable reproducibility for entropy and homogeneity (wCOV, 16.0% and 12.7%, respectively). On Bland-Altman analysis, no systematic increase or decrease between the scans was observed for either parameter (±1.96 SD: 1.07/-1.30, 0.23/-0.18, respectively). The remaining 27 tested radiomic metrics, however, achieved unacceptable high wCOV (≥21.7%). CONCLUSION: Many common radiomic features derived from a test-retest PET study had poor repeatability. Only Entropy and homogeneity achieved good repeatability, supporting the notion that those image biomarkers may be incorporated in future clinical trials. Those radiomic features based on high frequency aspects of images appear to lack the repeatability on PET to justify further study.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Masculino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Reproducibilidad de los Resultados , Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Medios de ContrasteRESUMEN
OBJECTIVES: We evaluated 18 F-DCFPyL test-retest repeatability of uptake in normal organs. METHODS: Twenty-two prostate cancer (PC) patients underwent two 18 F-DCFPyL PET scans within 7 days within a prospective clinical trial (NCT03793543). In both PET scans, uptake in normal organs (kidneys, spleen, liver, and salivary and lacrimal glands) was quantified. Repeatability was determined by using within-subject coefficient of variation (wCOV), with lower values indicating improved repeatability. RESULTS: For SUVmean , repeatability was high for kidneys, spleen, liver, and parotid glands (wCOV, range: 9.0%-14.3%) and lower for lacrimal (23.9%) and submandibular glands (12.4%). For SUVmax , however, the lacrimal (14.4%) and submandibular glands (6.9%) achieved higher repeatability, while for large organs (kidneys, liver, spleen, and parotid glands), repeatability was low (range: 14.1%-45.2%). CONCLUSION: We found acceptable repeatability of uptake on 18 F-DCFPyL PET for normal organs, in particular for SUVmean in the liver or parotid glands. This may have implications for both PSMA-targeted imaging and treatment, as patient selection for radioligand therapy and standardized frameworks for scan interpretation (PROMISE, E-PSMA) rely on uptake in those reference organs.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Humanos , Masculino , Lisina , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico por imagen , UreaRESUMEN
PURPOSE: The aim of this study was to investigate very early radiographic PSMA PET response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) and to assess its role in predicting overall response and survival. METHODS: This retrospective study enrolled 40 mCRPC patients who were treated with a median of 3 (2-9) [177Lu]Lu-PSMA I&T RLT cycles. Biochemical response was based on the relative change of serum PSA according to PCWG3 criteria, while radiographic response referred to the relative change of PSMA-derived total viable tumor volumes expressed as total lesion PSMA (TLP). RESULTS: After one cycle of RLT, biochemical partial response (PR) was seen in 8/40 (20.0%), stable disease (SD) in 22/40 (55.0%), and progressive disease (PD) in 10/40 (25%) patients. In PSMA PET, very early molecular PR was observed in 12 (30.0%), SD in 19 (47.5%), and PD in 9 (22.5%) subjects. The PSA and TLP nadir were achieved after a median of 1 (1-5) and 2 (1-6) cycles, respectively. Nineteen (47.5%) patients showed overall biochemical PR, 11 (27.5%) had SD, and 10 (25%) experienced PD. In PSMA-directed PET, 4 patients experienced molecular complete response (CR), 24 (60.0%) had PR, 4 (10.0%) SD, and 8 (20.0%) PD. Early biochemical or radiographic response was not associated with longer overall survival (OS). Overall biochemical responders had a nearly significantly longer median OS (22.7 months) than non-responders (14.4 months, p = 0.08). Early PSA progression was associated with shorter OS (12.2 months), compared to biochemical SD/PR (18.7 months, p = 0.09). CONCLUSION: In this retrospective cohort, there was no association between early PSMA PET radiographic response and overall survival; hence, treatment should not be prematurely discontinued. In contrast, early PSA progression after one cycle of [177Lu]Lu-PSMA I&T RLT was an indicator of overall progression and poor clinical outcome.
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Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Estudios Retrospectivos , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Resultado del Tratamiento , Antígeno Prostático Específico , Dipéptidos/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Lutecio/uso terapéuticoRESUMEN
Objectives: In patients with prostate cancer (PC) receiving prostate-specific membrane antigen- (PSMA-) targeted radioligand therapy (RLT), higher baseline standardized uptake values (SUVs) are linked to improved outcome. Thus, readers deciding on RLT must have certainty on the repeatability of PSMA uptake metrics. As such, we aimed to evaluate the test-retest repeatability of lesion uptake in a large cohort of patients imaged with 18F-DCFPyL. Methods: In this prospective, IRB-approved trial (NCT03793543), 21 patients with history of histologically proven PC underwent two 18F-DCFPyL PET/CTs within 7 days (mean 3.7, range 1 to 7 days). Lesions in the bone, lymph nodes (LN), and other organs were manually segmented on both scans, and uptake parameters were assessed (maximum (SUVmax) and mean (SUVmean) SUVs), PSMA-tumor volume (PSMA-TV), and total lesion PSMA (TL-PSMA, defined as PSMA - TV × SUVmean)). Repeatability was determined using Pearson's correlations, within-subject coefficient of variation (wCOV), and Bland-Altman analysis. Results: In total, 230 pairs of lesions (177 bone, 38 LN, and 15 other) were delineated, demonstrating a wide range of SUVmax (1.5-80.5) and SUVmean (1.4-24.8). Including all sites of suspected disease, SUVs had a strong interscan correlation (R 2 ≥ 0.99), with high repeatability for SUVmean and SUVmax (wCOV, 7.3% and 12.1%, respectively). High SUVs showed significantly improved wCOV relative to lower SUVs (P < 0.0001), indicating that high SUVs are more repeatable, relative to the magnitude of the underlying SUV. Repeatability for PSMA-TV and TL-PSMA, however, was low (wCOV ≥ 23.5%). Across all metrics for LN and bone lesions, interscan correlation was again strong (R 2 ≥ 0.98). Moreover, LN-based SUVmean also achieved the best wCOV (3.8%), which was significantly reduced when compared to osseous lesions (7.8%, P < 0.0001). This was also noted for SUVmax (wCOV, LN 8.8% vs. bone 12.0%, P < 0.03). On a compartment-based level, wCOVs for volumetric features were ≥22.8%, demonstrating no significant differences between LN and bone lesions (PSMA-TV, P =0.63; TL-PSMA, P =0.9). Findings on an entire tumor burden level were also corroborated in a hottest lesion analysis investigating the SUVmax of the most intense lesion per patient (R 2, 0.99; wCOV, 11.2%). Conclusion: In this prospective test-retest setting, SUV parameters demonstrated high repeatability, in particular in LNs, while volumetric parameters demonstrated low repeatability. Further, the large number of lesions and wide distribution of SUVs included in this analysis allowed for the demonstration of a dependence of repeatability on SUV, with higher SUVs having more robust repeatability.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Humanos , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico por imagen , Carga TumoralRESUMEN
BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is increasingly incorporated in the therapeutic algorithm of patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to elucidate the predictive performance of early biochemical response for overall survival (OS). MATERIALS AND METHODS: In this bicentric analysis, we included 184 mCRPC patients treated with 177 Lu-PSMA RLT. Response to treatment was defined as decrease in prostate-specific antigen (PSA) levels 8 weeks after the first cycle of RLT (any decline or >50% according to Prostate Cancer Working Group 3). OS of responders and nonresponders was then compared using Kaplan-Meier curves and log-rank comparison. RESULTS: A total of 114/184 patients (62.0%) showed any PSA decline (PSA response >50%, 55/184 [29.9%]). For individuals exhibiting a PSA decline >50%, OS of 19 months was significantly longer relative to nonresponders (13 months; hazard ratio of death [HR] = 0.64, 95% confidence interval [95% CI] = 0.44-0.93; p = 0.02). However, the difference was even more pronounced for any PSA decline, with an OS of 19 months in responders, but only 8 months in nonresponders (HR = 0.39, 95% CI = 0.25-0.60; p < 0.001). CONCLUSIONS: In mCRPC patients scheduled for RLT, early biochemical response was tightly linked to prolonged survival, irrespective of the magnitude of PSA decline. As such, even in patients with PSA decrease of less than 50%, RLT should be continued.
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Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración , Antígenos de Superficie , Dipéptidos/uso terapéutico , Glutamato Carboxipeptidasa II , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Humanos , Lutecio/uso terapéutico , Masculino , Próstata/patología , Neoplasias de la Próstata Resistentes a la Castración/patología , Estudios Retrospectivos , Sobrevivientes , Resultado del TratamientoRESUMEN
INTRODUCTION: In men with metastatic castration-resistant prostate cancer (mCRPC) scheduled for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), biochemical response is assessed based on repeated measurements of prostate-specific antigen (PSA) levels. We aimed to determine overall survival (OS) in patients experiencing sustained PSA increase, decrease, or fluctuations during therapy. MATERIALS AND METHODS: In this bicentric study, we included 176 mCRPC patients treated with PSMA-directed RLT. PSA levels were determined using blood samples prior to the first RLT and on the admission days for the following cycles. We calculated relative changes in PSA levels compared to baseline. Kaplan-Meier curves as well as log-rank test were used to compare OS of different subgroups, including patients with sustained PSA increase, decrease, or fluctuations (defined as change after initial decrease or increase after the first cycle). RESULTS: Sixty-one out of one hundred seventy-six (34.7%) patients showed a sustained increase and 86/176 (48.8%) a sustained decrease in PSA levels. PSA fluctuations were observed in the remaining 29/176 (16.5%). In this subgroup, 22/29 experienced initial PSA decrease followed by an increase (7/29, initial increase followed by a decrease). Median OS of patients with sustained decrease in PSA levels was significantly longer when compared to patients with sustained increase of PSA levels (19 vs. 8 months; HR 0.35, 95% CI 0.22-0.56; P < 0.001). Patients with PSA fluctuations showed a significantly longer median OS compared to patients with sustained increase of PSA levels (18 vs. 8 months; HR 0.49, 95% CI 0.30-0.80; P < 0.01), but no significant difference relative to men with sustained PSA decrease (18 vs. 19 months; HR 1.4, 95% CI 0.78-2.49; P = 0.20). In addition, in men experiencing PSA fluctuations, median OS did not differ significantly between patients with initial decrease or initial increase of tumor marker levels (16 vs. 18 months; HR 1.2, 95% CI 0.38-4.05; P = 0.68). CONCLUSION: Initial increase or decrease of PSA levels is sustained in the majority of patients undergoing RLT. Sustained PSA decrease was linked to prolonged survival and men with PSA fluctuations under treatment experienced comparable survival benefits. As such, transient tumor marker oscillations under RLT should rather not lead to treatment discontinuation, especially in the absence of radiological progression.
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Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Lutecio , Compuestos Heterocíclicos con 1 Anillo/efectos adversos , Neoplasias de la Próstata Resistentes a la Castración/patología , Dipéptidos/efectos adversos , Biomarcadores de Tumor , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Labelled with lutetium-177, the urea-based small molecules PSMA I&T and PSMA-617 are the two agents most frequently used for radioligand therapy (RLT) in patients with advanced metastatic castration-resistant and prostate-specific membrane antigen (PSMA) expressing prostate cancer (mCRPC). In this matched-pair analysis, we aimed to compare the toxicity and efficacy of both agents for PSMA-directed RLT. MATERIALS AND METHODS: A total of 110 mCRPC patients from two centres were accrued, 55 individuals treated with [177Lu]Lu-PSMA I&T, and a matched cohort of 55 patients treated with [177Lu]Lu-PSMA-617. Matching criteria included age at the first cycle, Gleason score, prostate-specific antigen (PSA) values, and previous taxane-based chemotherapy. Using common terminology criteria for adverse events (CTCAE v. 5.0), toxicity profiles were investigated (including bone marrow and renal toxicity). Overall survival (OS) between both groups was compared. RESULTS: Toxicity assessment revealed grade III anaemia in a single patient (1.8%) for [177Lu]Lu-PSMA I&T and five (9.1%) for [177Lu]Lu-PSMA-617. In addition, one (1.9%) grade III thrombopenia for [177Lu]Lu-PSMA-617 was recorded. Apart from that, no other grade III/IV toxicities were present. A median OS of 12 months for patients treated with [177Lu]Lu-PSMA I&T did not differ significantly when compared to patients treated with [177Lu]Lu-PSMA-617 (median OS, 13 months; P = 0.89). CONCLUSION: In this matched-pair analysis of patients receiving one of the two agents most frequently applied for PSMA RLT, the rate of clinically relevant toxicities was low for both compounds. In addition, no relevant differences for OS were observed.
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Neoplasias de la Próstata Resistentes a la Castración , Dipéptidos/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Humanos , Lutecio/uso terapéutico , Masculino , Análisis por Apareamiento , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/patología , Resultado del Tratamiento , Urea/análogos & derivados , Urea/uso terapéuticoRESUMEN
INTRODUCTION: This study aimed to test the diagnostic significance of FET-PET imaging combined with machine learning for the differentiation between multiple sclerosis (MS) and glioma II°-IV°. METHODS: Our database was screened for patients in whom FET-PET imaging was performed for the diagnostic workup of newly diagnosed lesions evident on MRI and suggestive of glioma. Among those, we identified patients with histologically confirmed glioma II°-IV°, and those who later turned out to have MS. For each group, tumor-to-brain ratio (TBR) derived features of FET were determined. A support vector machine (SVM) based machine learning algorithm was constructed to enhance classification ability, and Receiver Operating Characteristic (ROC) analysis with area under the curve (AUC) metric served to ascertain model performance. RESULTS: A total of 41 patients met selection criteria, including seven patients with MS and 34 patients with glioma. TBR values were significantly higher in the glioma group (TBRmax glioma vs. MS: p = 0.002; TBRmean glioma vs. MS: p = 0.014). In a subgroup analysis, TBR values significantly differentiated between MS and glioblastoma (TBRmax glioblastoma vs. MS: p = 0.0003, TBRmean glioblastoma vs. MS: p = 0.0003) and between MS and oligodendroglioma (ODG) (TBRmax ODG vs. MS: p = 0.003; TBRmean ODG vs. MS: p = 0.01). The ability to differentiate between MS and glioma II°-IV° increased from 0.79 using standard TBR analysis to 0.94 using a SVM based machine learning algorithm. CONCLUSIONS: FET-PET imaging may help differentiate MS from glioma II°-IV° and SVM based machine learning approaches can enhance classification performance.
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Neoplasias Encefálicas/diagnóstico por imagen , Glioma/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Aprendizaje Automático , Esclerosis Múltiple/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiofármacos , Tirosina/análogos & derivadosRESUMEN
An intake monitoring program covering more than half a year of clinical administration of Radium-223-dichloride for the palliative treatment of castration-resistant prostate cancer was carried out in the nuclear medicine department of the university hospital Bonn. Radioactivity in a total of 87 samples of gloves, air filters, faecal bioassays and face masks was measured and evaluated to assess the need for radiation protection measures for the medical staff. The main aim was to quantify or obtain an upper limit for the intake factor. An intake factor of 10-8 was measured when the preparation of patient doses took place in part in a laminar flow cabinet, which indicates an intake factor of 10-7 in more commonplace practice without a cabinet. The intake factor is therefore at the same level as other standard applications of unsealed sources in nuclear medicine. Our findings confirmed that masks are not required under any circumstances. However, the investigation also revealed that contamination risks, especially during the preparation of doses in syringes, should not be neglected.
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Antineoplásicos/administración & dosificación , Exposición Profesional/análisis , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radioisótopos/análisis , Radio (Elemento)/administración & dosificación , Humanos , Masculino , Radioisótopos/administración & dosificación , Medición de RiesgoRESUMEN
PURPOSE: Prostate specific membrane antigen is expressed by the endothelium of many tumors. The aim of the study was to find a rationale for prostate specific membrane antigen based imaging and investigate the prognostic role of vascular prostate specific membrane antigen expression in patients with renal cell carcinoma. MATERIALS AND METHODS: A total of 257 patients with renal cell carcinoma were included in study with a median followup exceeding 10.0 years. Prostate specific membrane antigen expression on tumor vessels was detected by immunohistochemistry. Vascular expression of FOLH1 gene (prostate specific membrane antigen) mRNA was investigated in clear cell carcinoma and papillary renal cell carcinoma using TCGA (The Cancer Genome Atlas) data. RESULTS: Endothelial prostate specific membrane antigen protein expression was higher in clear cell than in papillary and chromophobe renal cell carcinoma. Higher grade and stage, metastatic and lethal clear cell renal cell carcinoma showed higher prostate specific membrane antigen expression in tumor vessels. On univariate and multivariate analysis the intensity of positive vs negative endothelial prostate specific membrane antigen protein expression was significantly associated with overall survival. TCGA based analyses confirmed the prognostic role of vascular expression of FOLH1 mRNA. The analyses also supported the usefulness of prostate specific membrane antigen based imaging in cases of clear cell but not papillary renal cell carcinoma. CONCLUSIONS: We provide a rationale for further development of prostate specific membrane antigen targeted imaging in patients with clear cell renal cell carcinoma. The prognostic role of prostate specific membrane antigen was determined at the protein level in clear cell renal cell carcinoma and at the mRNA level in clear cell and papillary renal cell carcinoma.
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Antígenos de Superficie/metabolismo , Biomarcadores de Tumor/metabolismo , Vasos Sanguíneos/metabolismo , Carcinoma de Células Renales/metabolismo , Glutamato Carboxipeptidasa II/metabolismo , Neoplasias Renales/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
PURPOSE: The purpose of our study was to show the feasibility and potential benefits of using 68Ga-PSMA-PET/CT imaging for radiation therapy treatment planning of patients with primary prostate cancer using either integrated boost on the PET-positive volume or localized treatment of the PET-positive volume. The potential gain of such an approach, the improvement of tumor control, and reduction of the dose to organs-at-risk at the same time was analyzed using the QUANTEC biological model. METHODS: Twenty-one prostate cancer patients (70 years average) without previous local therapy received 68Ga-PSMA-PET/CT imaging. Organs-at-risk and standard prostate target volumes were manually defined on the obtained datasets. A PET active volume (PTV_PET) was segmented with a 40% of the maximum activity uptake in the lesion as threshold followed by manual adaption. Five different treatment plan variations were calculated for each patient. Analysis of derived treatment plans was done according to QUANTEC with in-house developed software. Tumor control probability (TCP) and normal tissue complication probability (NTCP) was calculated for all plan variations. RESULTS: Comparing the conventional plans to the plans with integrated boost and plans just treating the PET-positive tumor volume, we found that TCP increased to (95.2 ± 0.5%) for an integrated boost with 75.6 Gy, (98.1 ± 0.3%) for an integrated boost with 80 Gy, (94.7 ± 0.8%) for treatment of PET-positive volume with 75 Gy, and to (99.4 ± 0.1%) for treating PET-positive volume with 95 Gy (all p < 0.0001). For the integrated boost with 80 Gy, a significant increase of the median NTCP of the rectum was found, for all other plans no statistical significant increase in the NTCP neither of the rectum nor the bladder was found. CONCLUSIONS: Our study demonstrates that the use of 68Ga-PSMA-PET/CT image information allows for more individualized prostate treatment planning. TCP values of identified active tumor volumes were increased, while rectum and bladder NTCP values either remained the same or were even lower. However, further studies need to clarify the clinical benefit for the patients applying these techniques.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/radioterapia , Radioterapia de Intensidad Modulada , Anciano , Anciano de 80 o más Años , Alemania , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/diagnóstico por imagen , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: To implement and evaluate a dedicated receiver array coil for simultaneous positron emission tomography/magnetic resonance (PET/MR) imaging in breast cancer. METHODS: A 16-channel receiver coil design was optimized for simultaneous PET/MR imaging. To assess MR performance, the signal-to-noise ratio, parallel imaging capability and image quality was evaluated in phantoms, volunteers and patients and compared to clinical standard protocols. For PET evaluation, quantitative (18) F-FDG PET images of phantoms and seven patients (14 lesions) were compared to images without the coil. In PET image reconstruction, a CT-based template of the coil was combined with the MR-acquired attenuation correction (AC) map of the phantom/patient. RESULTS: MR image quality was comparable to clinical MR-only examinations. PET evaluation in phantoms showed regionally varying underestimation of the standardised uptake value (SUV; mean 22 %) due to attenuation caused by the coil. This was improved by implementing the CT-based coil template in the AC (<2 % SUV underestimation). Patient data indicated that including the coil in the AC increased the SUV values in the lesions (21 ± 9 %). CONCLUSIONS: Using a dedicated PET/MR breast coil, state-of-the-art MRI was possible. In PET, accurate quantification and image homogeneity could be achieved if a CT-template of this coil was included in the AC for PET image reconstruction. KEY POINTS: ⢠State-of-the-art breast MRI using a dedicated PET/MR breast coil is feasible. ⢠A multi-channel design facilitates shorter MR acquisition times via parallel imaging. ⢠An MR coil inside a simultaneous PET/MR system causes PET photon attenuation. ⢠Including a coil CT-template in PET image reconstruction results in recovering accurate quantification.
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Neoplasias de la Mama/diagnóstico , Imagen por Resonancia Magnética/instrumentación , Imagen por Resonancia Magnética/métodos , Imagen Multimodal/métodos , Tomografía de Emisión de Positrones/métodos , Mama/diagnóstico por imagen , Mama/patología , Diseño de Equipo , Femenino , Fluorodesoxiglucosa F18 , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Persona de Mediana Edad , Fantasmas de Imagen , Radiofármacos , Reproducibilidad de los Resultados , Relación Señal-RuidoRESUMEN
While functional imaging with [18F]Fluoro-deoxy-glucose positron emission tomography (PET)/computed tomography is a well-established imaging modality in most lymphoma entities, novel tracers addressing cell surface receptors, tumor biology, and the microenvironment are being developed. Especially, with the emergence of immuno-PET targeting surface markers of lymphoma cells, a new imaging modality of immunotherapies is evolving, which might especially aid in relapsed and refractory disease stages. This review highlights different new PET tracers in indolent and aggressive lymphoma subtypes and summarizes the current state of immuno-PET imaging in lymphoma.
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Because of the need for radiolabeled theranostics for the detection and treatment of medullary thyroid cancer (MTC), and the yet unresolved stability issues of minigastrin analogs targeting the cholecystokinin-2 receptor (CCK-2R), our aim was to address in vivo stability, our motivation being to develop and evaluate DOTA-CCK-66 (DOTA-γ-glu-PEG3-Trp-(N-Me)Nle-Asp-1-Nal-NH2, PEG: polyethylene glycol) and DOTA-CCK-66.2 (DOTA-glu-PEG3-Trp-(N-Me)Nle-Asp-1-Nal-NH2), both derived from DOTA-MGS5 (DOTA-glu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1-Nal-NH2), and clinically translate [68Ga]Ga-DOTA-CCK-66. Methods: 64Cu and 67Ga labeling of DOTA-CCK-66, DOTA-CCK-66.2, and DOTA-MGS5 was performed at 90°C within 15 min (1.0 M NaOAc buffer, pH 5.5, and 2.5 M 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer, respectively). 177Lu labeling of these 3 compounds was performed at 90°C within 15 min (1.0 M NaOAc buffer, pH 5.5, 0.1 M sodium ascorbate). CCK-2R affinity of natGa/natCu/natLu-labeled DOTA-CCK-66, DOTA-CCK-66.2, and DOTA-MGS5 was examined on AR42J cells. The in vivo stability of 177Lu-labeled DOTA-CCK-66 and DOTA-MGS5 was examined at 30 min after injection in CB17-SCID mice. Biodistribution studies at 1 h ([67Ga]Ga-DOTA-CCK-66) and 24 h ([177Lu]Lu-DOTA-CCK-66/DOTA-MGS5) after injection were performed on AR42J tumor-bearing CB17-SCID mice. In a translation to the human setting, [68Ga]Ga-DOTA-CCK-66 was administered and whole-body PET/CT was acquired at 120 min after injection in 2 MTC patients. Results: Irrespective of the metal or radiometal used (copper, gallium, lutetium), high CCK-2R affinity (half-maximal inhibitory concentration, 3.6-6.0 nM) and favorable lipophilicity were determined. In vivo, increased numbers of intact peptide were found for [177Lu]Lu-DOTA-CCK-66 compared with [177Lu]Lu-DOTA-MGS5 in murine urine (23.7% ± 9.2% vs. 77.8% ± 2.3%). Overall tumor-to-background ratios were similar for both 177Lu-labeled analogs. [67Ga]Ga-DOTA-CCK-66 exhibited accumulation (percentage injected dose per gram) that was high in tumor (19.4 ± 3.5) and low in off-target areas (blood, 0.61 ± 0.07; liver, 0.31 ± 0.02; pancreas, 0.23 ± 0.07; stomach, 1.81 ± 0.19; kidney, 2.51 ± 0.49) at 1 h after injection. PET/CT examination in 2 MTC patients applying [68Ga]Ga-DOTA-CCK-66 confirmed multiple metastases. Conclusion: Because of the high in vivo stability and favorable overall preclinical performance of [nat/67Ga]Ga-/[nat/177Lu]Lu-DOTA-CCK-66, a proof-of-concept clinical investigation of [68Ga]Ga-DOTA-CCK-66 was completed. As several lesions could be identified and excellent biodistribution patterns were observed, further patient studies applying [68Ga]Ga- and [177Lu]Lu-DOTA-CCK-66 are warranted.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Tiroides , Humanos , Animales , Ratones , Radioisótopos de Galio/química , Distribución Tisular , Cobre , Ratones SCID , Neoplasias de la Tiroides/diagnóstico por imagen , Receptor de Colecistoquinina B/metabolismoRESUMEN
BACKGROUND: In patients with prostate cancer (PCa), imaging with gastrin-releasing peptide receptor (GRPR) ligands is an alternative to PSMA-targeted tracers, particularly if PSMA expression is low or absent. [99mTc]Tc-N4-BTG is a newly developed GRPR-directed probe for conventional scintigraphy and single photon emission computed tomography (SPECT) imaging. The current study aims to investigate the safety, biodistribution and dosimetry of [99mTc]Tc-N4-BTG in patients with biochemical recurrence (BCR) of PCa. RESULTS: No adverse pharmacologic effects were observed. Injection of [99mTc]Tc-N4-BTG resulted in an effective dose of 0.0027 ± 0.0002 mSv/MBq. The urinary bladder was the critical organ with the highest mean absorbed dose of 0.028 ± 0.001 mGy/MBq, followed by the pancreas with 0.0043 ± 0.0015 mGy/MBq, osteogenic cells with 0.0039 ± 0.0005 mGy/MBq, the kidneys with 0.0034 ± 0.0003 mGy/MBq, and the liver with 0.0019 ± 0.0004 mGy/MBq, respectively. No focal tracer uptake suggestive of PCa recurrence could be revealed for any of the patients. CONCLUSION: [99mTc]Tc-N4-BTG appears to be a safe diagnostic agent. Compared to GRPR-targeted PET tracers, this 99mTc-labelled SPECT agent could contribute to a broader application and better availability of this novel approach. Further research to assess its clinical value is warranted.
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ABSTRACT: Cholecystokinin 2 receptor (CCK2R) is a promising target for imaging and treatment of medullary thyroid cancer due to its overexpression in over 90% of tumor cells. 68Ga-DOTA-CCK-66 is a recently introduced PET tracer selective for CCK2R, which has shown favorable pharmacokinetics in vivo in preclinical experiments. In order to further investigate safety and suitability of this tracer in the human setting, whole-body distribution and radiation dosimetry were evaluated. PATIENTS AND METHODS: Six patients with a history of medullary thyroid cancer were injected intravenously with 169 ± 19 MBq of 68Ga-DOTA-CCK-66. Whole-body PET/CT scans were acquired at 10 minutes, 1 hour, 2 hours, and 4 hours after tracer injection. Time-activity curves per organ were determined, and mean organ-absorbed doses and effective doses were calculated using OLINDA/EXM. RESULTS: Injection of a standard activity of 150 MBq of 68Ga-DOTA-CCK-66 results in an effective dose of 4.5 ± 0.9 mSv. The highest absorbed organ doses were observed in the urinary bladder wall (40 mGy) and the stomach (15 mGy), followed by the kidneys (6 mGy), as well as the liver and the spleen (3 mGy each). CCK2R-expressing tumor manifestations could be detected in 2 of the 6 patients, including lymph node, bone, and liver metastases. CONCLUSIONS: 68Ga-DOTA-CCK-66 exhibits a favorable dosimetry. Beyond physiologic receptor expression of the stomach, no other relevant tracer accumulation could be observed, rendering this organ at risk in case of subsequent radioligand therapy using 177Lu-DOTA-CCK-66.
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C-X-C motif chemokine receptor 4 (CXCR4)-directed molecular imaging provides excellent read-out capabilities in patients with marginal zone lymphoma (MZL). We aimed to determine the interobserver agreement rate of CXCR4-targeted PET/CT among readers with different levels of experience. METHODS: 50 subjects with MZL underwent CXCR4-targeted PET/CT, which were reviewed by four readers (including two experienced and two less experienced observers). The following 8 parameters were investigated: overall scan result, CXCR4 density in lymphoma tissue, extranodal organ involvement, No. of affected extranodal organs and extranodal organ metastases, lymph node (LN) involvement and No. of affected LN areas and LN metastases. We applied intraclass correlation coefficients (ICC; < 0.4, poor; 0.4-0.59, fair; 0.6-0.74, good and > 0.74 excellent agreement rates). RESULTS: Among all readers, fair agreement was recorded for No. of affected extranodal organs (ICC, 0.40; 95% confidence interval [CI], 0.25-0.68), overall scan result (ICC, 0.42; 95%CI, 0.28-0.57), CXCR4 density in lymphoma tissue (ICC, 0.52; 95%CI, 0.38-0.66), and No. of extranodal organ metastases (ICC, 0.55; 95%CI, 0.41-0.61) and LN involvement (ICC, 0.59; 95%CI, 0.46-0.71). Good agreement rates were observed for No. of LN metastases (ICC, 0.71; 95%CI, 0.60-0.81) and No. of LN areas (ICC, 0.73; 95%CI, 0.63-0.82), while extranodal organ involvement (ICC, 0.35; 95%CI, 0.21-0.51) achieved poor concordance. On a reader-by-reader comparison, the experienced readers achieved significantly higher agreement rates in 4/8 (50%) investigated scan items (ICC, range, 0.21-0.90, P < / = 0.04). In the remaining 4/8 (50%), a similar trend with higher ICCs for the experienced readers was recorded (n.s.). CONCLUSION: CXCR4-directed PET/CT mainly provided fair to good agreement rates for scan assessment, while a relevant level of experience seems to be required for an accurate imaging read-out.