18F-PSMA-1007 multiparametric, dynamic PET/CT in biochemical relapse and progression of prostate cancer.

OBJECTIVES: Aim of the present analysis is to investigate the biodistribution and pharmacokinetics of the recently clinically introduced radioligand 18F-PSMA-1007 in patients with biochemical recurrence or progression of prostate cancer (PC) by means of multiparametric (dynamic and whole-body) PET/CT. METHODS: Twenty-five (25) patients with PC biochemical relapse or progression (median age = 66.0 years) were enrolled in the analysis. The median PSA value was 1.2 ng/mL (range = 0.1-237.3 ng/mL) and the median Gleason score was 7 (range = 6-10). All patients underwent dynamic PET/CT (dPET/CT) scanning (60 min) of the pelvis and lower abdomen as well as whole-body PET/CT with 18F-PSMA-1007. PET/CT assessment was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a two-tissue compartment model and fractal analysis. RESULTS: 15/25 patients were PET-positive. Plasma PSA values in the 18F-PSMA-1007 positive group were higher (median = 3.6 ng/mL; range = 0.2-237.3 ng/mL) than in the 18F-PSMA-1007 negative group (median value = 0.7 ng/mL; range = 0.1-3.0 ng/mL). Semi-quantitative analysis in the PC lesions demonstrated a mean SUVaverage = 25.1 (median = 15.4; range = 3.5-119.2) and a mean SUVmax = 41.5 (median = 25.7; range = 3.8-213.2). Time-activity curves derived from dPET/CT revealed an increasing tracer accumulation during the 60 min of dynamic PET acquisition into the PC lesions, higher than in the urinary bladder and the colon. Significant correlations were observed between 18F-PSMA-1007 uptake (SUV), influx, and fractal dimension (FD). CONCLUSIONS: 18F-PSMA-1007 PET/CT could detect PC lesions in 60% of the patients of a mixed population, including also patients with very low PSA values. Higher PSA values were associated with a higher detection rate. Dynamic PET analysis revealed an increasing tracer uptake during the dynamic PET acquisition as well as high binding and internalization of the radiofluorinated PSMA ligand in the PC lesions.

Intra-individual comparison of (68)Ga-PSMA-11-PET/CT and multi-parametric MR for imaging of primary prostate cancer.

PURPOSE: Multi-parametric magnetic resonance imaging (MP-MRI) is currently the most comprehensive work up for non-invasive primary tumor staging of prostate cancer (PCa). Prostate-specific membrane antigen (PSMA)-Positron emission tomography-computed tomography (PET/CT) is presented to be a highly promising new technique for N- and M-staging in recurrent PCa-patients. The actual investigation analyses the potential of (68)Ga-PSMA11-PET/CT to assess the extent of primary prostate cancer by intra-individual comparison to MP-MRI. METHODS: In a retrospective study, ten patients with primary PCa underwent MP-MRI and PSMA-PET/CT for initial staging. All tumors were proven histopathological by biopsy. Image analysis was done in a quantitative (SUVmax) and qualitative (blinded read) fashion based on PI-RADS. The PI-RADS schema was then translated into a 3D-matrix and the euclidian distance of this coordinate system was used to quantify the extend of agreement. RESULTS: Both MP-MRI and PSMA-PET/CT presented a good allocation of the PCa, which was also in concordance to the tumor location validated in eight-segment resolution by biopsy. An Isocontour of 50 % SUVmax in PSMA-PET resulted in visually concordant tumor extension in comparison to MP-MRI (T2w and DWI). For 89.4 % of sections containing a tumor according to MP-MRI, the tumor was also identified in total or near-total agreement (euclidian distance ≤1) by PSMA-PET. Vice versa for 96.8 % of the sections identified as tumor bearing by PSMA-PET the tumor was also found in total or near-total agreement by MP-MRI. CONCLUSIONS: PSMA-PET/CT and MP-MRI correlated well with regard to tumor allocation in patients with a high pre-test probability for large tumors. Further research will be needed to evaluate its value in challenging situation such as prostatitis or after repeated negative biopsies.

PSMA PET/CT with Glu-urea-Lys-(Ahx)-[68Ga(HBED-CC)] versus 3D CT volumetric lymph node assessment in recurrent prostate cancer.

PURPOSE: PET/CT with the PSMA ligand is a powerful new method for the early detection of nodal metastases in patients with biochemical relapse. The purpose of this retrospective investigation was to evaluate the volume and dimensions of nodes identified by Glu-urea-Lys-(Ahx)-[(68)Ga(HBED-CC)] ((68)Ga-PSMA-11) in the setting of recurrent prostate cancer. METHODS: All PET/CT images were acquired 60 ± 10 min after intravenous injection of (68)Ga-PSMA-11 (mean dose 176 MBq). In 21 patients with recurrent prostate cancer and rising PSA, 49 PSMA-positive lymph nodes were identified. Using semiautomated lymph node segmentation software, node volume and short-axis and long-axis dimensions were measured and compared with the maximum standardized uptake values (SUVmax). Round nodes greater than or equal to 8 mm were considered positive by morphological criteria alone. The percentage of nodes identified by elevated SUVmax but not by conventional morphological criteria was determined. RESULTS: The mean volume of (68)Ga-PSMA-11-positive nodes was 0.5 ml (range 0.2 - 2.3 ml), and the mean short-axis diameter was 5.8 mm (range 2.4 - 13.3 mm). In 7 patients (33.3 %) with 31 PSMA-positive nodes only 11 (36 %) were morphologically positive based on diameters >8 mm on CT. In the remaining 14 patients (66.7 %), 18 (37 %) of PSMA positive lymph nodes had short-axis diameters <8 mm with a mean short-axis diameter of 5.0 mm (range 2.4 - 7.9 mm). Thus, in this population, (68)Ga-PSMA-11 PET/CT detected nodal recurrence in two-thirds of patients who would have been missed using conventional morphological criteria. CONCLUSION: (68)Ga-PSMA-11 PET/CT is more sensitive than CT based 3D volumetric lymph node evaluation in determining the node status of patients with recurrent prostate cancer, and is a promising method of restaging prostate cancers in this setting.

Comparison of PET/CT and PET/MRI hybrid systems using a 68Ga-labelled PSMA ligand for the diagnosis of recurrent prostate cancer: initial experience.

PURPOSE: (68)Ga-labelled HBED-CC-PSMA is a highly promising tracer for imaging recurrent prostate cancer (PCa). The intention of this study was to evaluate the feasibility of PET/MRI with this tracer. METHODS: Twenty patients underwent PET/CT 1 h after injection of the (68)Ga-PSMA ligand followed by PET/MRI 3 h after injection. Data from the two investigations were first analysed separately and then compared with respect to tumour detection rate and radiotracer uptake in various tissues. To evaluate the quantification accuracy of the PET/MRI system, differences in SUVs between PET/CT and corresponding PET/MRI were compared with differences in SUVs between PET/CT 1 h and 3 h after injection in another patient cohort. This cohort was investigated using the same PET/CT system. RESULTS: With PET/MRI, different diagnostic sequences, higher contrast of lesions and higher resolution of MRI enabled a subjectively easier evaluation of the images. In addition, four unclear findings on PET/CT could be clarified as characteristic of PCa metastases by PET/MRI. However, in PET images of the PET/MRI, a reduced signal was observed at the level of the kidneys (in 11 patients) and around the urinary bladder (in 15 patients). This led to reduced SUVs in six lesions. SUVmean values provided by the PET/MRI system were different in muscles, blood pool, liver and spleen. CONCLUSION: PCa was detected more easily and more accurately with Ga-PSMA PET/MRI than with PET/CT and with lower radiation exposure. Consequently, this new technique could clarify unclear findings on PET/CT. However, scatter correction was challenging when the specific (68)Ga-PSMA ligand was used. Moreover, direct comparison of SUVs from PET/CT and PET/MR needs to be conducted carefully.

PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions.

PURPOSE: Prostate-specific membrane antigen (PSMA) is a cell surface protein with high expression in prostate carcinoma (PC) cells. Recently, procedures have been developed to label PSMA ligands with (68)Ga, (99m)Tc and (123/124/131)I. Our initial experience with Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)]((68)Ga-PSMA) suggests that this novel tracer can detect PC relapses and metastases with high contrast. The aim of this study was to investigate its biodistribution in normal tissues and tumour lesions. METHODS: A total of 37 patients with PC and rising prostate-specific antigen (PSA) levels were subjected to (68)Ga-PSMA positron emission tomography (PET)/CT. Quantitative assessment of tracer uptake was performed 1 and 3 h post-injection (p.i.) by analysis of mean and maximum standardized uptake values (SUVmean/max) of several organs and 65 tumour lesions. Subsequently, tumour to background ratios were calculated. RESULTS: The PET/CT images showed intense tracer uptake in both kidneys and salivary glands. Moderate uptake was seen in lacrimal glands, liver, spleen and in small and large bowel. Quantitative assessment revealed excellent contrast between tumour lesions and most normal tissues. Of 37 patients, 31 (83.8 %) showed at least one lesion suspicious for cancer at a detection rate of 60 % at PSA <2.2 ng/ml and 100 % at PSA >2.2 ng/ml. Median tumour to background ratios were 18.8 (2.4-158.3) in early images and 28.3 (2.9-224.0) in late images. CONCLUSION: The biodistribution of the novel (68)Ga-PSMA tracer and its ability to detect PC lesions was analysed in 37 patients. Within healthy organs, kidneys and salivary glands demonstrated the highest radiotracer uptake. Lesions suspicious for PC presented with excellent contrast as early as 1 h p.i. with high detection rates even at low PSA levels.

[Potential of PET/MRI for diagnosis of prostate cancer]. / Potenziale der PET/MRT in der Diagnostik des Prostatakarzinoms.

CLINICAL/METHODICAL ISSUE: A present goal is to improve detection and staging of prostate cancer using innovative imaging technology such as PET/MRI. STANDARD RADIOLOGICAL METHODS: The modality of choice for detection of prostate cancer is multiparametric MRI. Furthermore, PET/CT is used, in particular, for the detection and staging of distant metastases and recurrent disease. For assessment of bone metastases, the method most commonly used is bone scintigraphy. METHODICAL INNOVATIONS: The development of a simultaneous hybrid PET/MRI system is the last great "fusion" of the known cross-sectional image modalities. In addition, synthesis of new, innovative tracers such as (18)F-FACBC or (68)Ga-PSMA allows more specific detection of prostate cancer. PERFORMANCE: Hybrid PET/MRI imaging has the potential to replace conventional imaging techniques in the future. ACHIEVEMENTS: The method is just starting the broad application. Clinical studies must be expanded in order to substantiate the additional value of the method. PRACTICAL RECOMMENDATIONS: Currently, there is still a low distribution situation, since it is a new and cost-intensive method. At the same time, there is still no consistent solution for reimbursement. The importance in practice first rises by clarifying the payment situation and further demonstration of the method's benefit by larger studies.

[Importance of PET/CT in lymphoma diagnostics]. / Stellenwert der PET/CT in der Lymphomdiagnostik.

CLINICAL/METHODICAL ISSUE: Staging or re-staging of lymphomas using conventional imaging modalities is based on morphological changes, usually on the diameter of lesions. However, vitality of tumors cannot be evaluated. STANDARD RADIOLOGICAL METHODS: In this context computed tomography (CT) has been used as a standard modality. METHODICAL INNOVATIONS: Since the introduction of positron emission tomography (PET), evaluation of tumor vitality has become possible. Moreover PET/CT hybrid scanners were brought onto the market one decade ago. PERFORMANCE: The fluorodeoxyglucose (FDG) PET/CT technique is now accepted as one of the most accurate modalities in the diagnosis of aggressive lymphomas due to a high FDG uptake (overall accuracy > 90%, sensitivity >90%). However, indolent lymphomas suffer from lower FDG uptake due to a moderate metabolic activity. After the introduction of PET/CT hybrid imaging the specificity of this diagnostic technique increased significantly compared to PET alone (from > 80% to > 90%). With the utilization of PET approximately 20% more lesions are detected when comparing to CT alone and in up to 15% of the patients this also results in a change of the therapeutic regime. As post-chemotherapy scar tissue usually persists for months, evaluation of vitality within residual bulks using FDG-PET can predict therapy response much earlier than CT, enabling therapy stratification. Other PET tracers apart from FDG have low impact in imaging of lymphomas and only the thymidine analogue fluorothymidine (FLT) is used in some cases for non-invasive measurement of proliferation. ACHIEVEMENTS: Despite the capability of FDG-PET/CT there is no evidence that the improvement in diagnostics is translated into a better patient outcome and therefore warrants the high costs. False positive findings in PET can result in unnecessary treatment escalation with subsequent higher therapy-associated toxicity and costs. PRACTICAL RECOMMENDATIONS: Some pitfalls can be avoided by scheduling PET scans carefully. As treatment-induced inflammation early after therapy can be misinterpreted as vital tumor tissue, it is recommended to wait at least 3 weeks between the last treatment cycle and the subsequent FDG-PET follow-up. Until the results of the prospective multicenter trials "PETAL" and "HD-18" become available, in Germany FDG-PET is only recommended generally for restaging Hodgkin's disease with a known rest bulk of > 2.5 cm in justifiable individual cases or in clinical trials.

[Prostate-specific membrane antigen (PSMA)-based diagnostics and treatment of prostate cancer]. / Prostataspezifische Membranantigen(PSMA)-basierte Diagnostik und Therapie des Prostatakarzinoms.

BACKGROUND: Since their clinical introduction in 2011, PSMA-PET/CT (PSMA: prostate-specific membrane antigen) as well as PSMA therapy of prostate cancer (PC) have spread rapidly worldwide. OBJECTIVES: To summarize the current knowledge about both PSMA-PET/CT and PSMA therapy of PC. METHODS: The knowledge derived from the literature as well as the authors' experiences were collected in this review. RESULTS: PSMA-PET/CT demonstrates a very high sensitivity and specificity for the detection of recurrent PC as well as for the primary staging of intermediate- and high-risk PC. PSMA therapy shows promising results in third-line treatment for patients with castration-resistant, metastatic PC. CONCLUSIONS: PSMA-PET/CT is meanwhile established as the gold standard for the detection of recurrent PC and is in the process of assuming the same role for primary staging of intermediate- to high-risk PC. PSMA therapy serves as a promising third-line therapy in an increasing number of centers.

SUV of [68Ga]DOTATOC-PET/CT Predicts Response Probability of PRRT in Neuroendocrine Tumors.

PURPOSE: The goal of our study was to quantify the expression of the somatostatin receptors (SSTR2) using the maximum standardized uptake value (SUVmax) of [(68)Ga]DOTA(0)-Phe(1)-Tyr(3)-octreotide (DOTATOC) positron emission tomography (PET)-computed tomography (CT) in liver metastases of patients with neuroendocrine tumors (NETs) prior to peptide receptor radiation therapy (PRRT) and compare the initial tumor uptake with the final treatment outcome. PROCEDURES: SSTR2 expression of the 60 liver metastases in 30 NET patients was assessed at baseline and after PRRT by measuring SUVmax, tumor to spleen ratio (T/S ratio), and tumor to liver ratio (T/L ratio). Based on morphological changes and tumor size measured at baseline and follow-up contrast-enhanced CT (after three cycles of PRRT), lesions were divided into two groups by the following: (i) responding (n = 40) and (ii) non-responding (n = 20). RESULTS: Statistically significant differences were observed in the mean SUVmax for non-responding vs. responding lesions at baseline (18.00 ± 3.59 vs. 33.55 ± 4.62, p < 0.05) and for the mean T/S ratio (1.20 ± 0.37 vs. 1.90 ± 0.45, p < 0.05) and the mean T/L ratio (3.15 ± 0.53 vs. 4.97 ± 0.62, p < 0.05). Using the receiver operating characteristic curves, SUVmax was found a better metric than both T/L ratio and T/S ratio (area under the curve (AUC) of SUVmax 0.87; T/L ratio 0.78; T/S ratio 0.73) as a stratification criterion. Using a threshold value of >16.4 for SUVmax, the sensitivity and specificity in predicting responding lesions were 95 and 60 %, respectively. CONCLUSION: We propose a SUVmax cutoff of >16.4 from [(68)Ga]DOTATOC-PET-CT to select patients for PRRT. A T/L ratio >2.2 might present a scanner-independent criterion that enables the translation of our results to other institutions. However, the robustness of this arbitrary unit still needs to be evaluated with different PET scanners.

Comparison of 68Ga-DOTATOC biodistribution in patients with and without spleenectomy.

AIM: Ga-68 labeled somatostatin analogues such as 68Ga-DOTA0-Phe1-Tyr3-octrotide (DOTATOC) as PET tracers, have significantly improved the imaging of somatostatin receptors (SSTRs) expressing tumors. Due to unspecific parenchymal binding and the expression of SSTRs on leukocytes in the spleen this is the organ with the highest non-tumor uptake of DOTATOC. Therefore, we investigated the potential changes of normal tissue distribution and tumor concentration in patients with neuroendocrine tumors (NETs) with or without spleenectomy. METHODS: Out of 420 patients with pancreatic NET undergoing 68GA-DOTATOC PET/CT eleven patients with and eleven patients without spleenectomy were derived and matched in regard to tumor histology, tumor load, age and gender. The SUV(max) of liver metastases as well as of the following normal tissues was determined: pituitary gland, thyroid gland, liver parenchyma, kidneys and suprarenal glands. RESULTS: SUV(max) values with and without spleenectomy were: in the liver metastasis (19.17 ± 6.05 versus 37.67 ± 16.31), in the thyroid gland (2.56 ± 1.33 versus 2.66 ± 0.94), in the pituitary gland (4.08 ± 1.79 versus 4.92 ± 1.93) in suprarenal glands (7.18 ± 3.33 versus 9.73 ± 3.46 on the left side and 7.32 ± 3.03 versus 11.19 ± 5.72 on the right side), in the kidneys (8.1 3 ± 4.26 on the left side and 8.11 ± 4.16 on the right side versus 8.62 ± 2.17 on the left side and 9.79 ± 2.18 on the right side) and in normal liver tissue (5.74 ± 1.55 versus 6.22 ± 1.95). The difference was statistically significant (Wilcoxon test P<0.05) in tumor lesions, adrenal and kidney tissue. CONCLUSION: Spleenectomy must be considered as a relevant factor when reporting the outcome of SSTR targeted diagnostics and therapies.

Impact of peptide receptor radionuclide therapy on the 68Ga-DOTATOC-PET/CT uptake in normal tissue.

AIM: Positron-emission tomography/computed tomography (PET/CT) with [68Ga]DOTA0-Phe1-Tyr3-octreotide (68Ga-DOTA-TOC) became a standard for somatostatin receptor imaging. We investigated the potential changes of normal tissue uptake in patients with neuroendocrine tumor undergoing peptide receptor radionuclide therapy (PRRT). METHODS: Sixteen patients underwent [68Ga]-DOTA-TOC-PET/CT prior and after 4-6 cycles of PRRT (mean administered activity: 13.8 GBq 90Y+ 9.6 177Lu). The maximum standardized uptake values (SUVmax) of pituitary, thyroid, spleen, liver parenchyma, pancreas, kidneys and adrenals were determined, respectively. RESULTS: SUVmax values prior and after PRRT were in pituitary (5, 56±2,91/ 4,47±2,53), thyroid (2.05±1.11/ 2.49±2.47), spleen (24.95±14.20/20.06±8.53), liver (7.13±3.96/6.62±2.63), pancreas (6.96±1.99/6.83±2.00), kidneys (13.0±3.85/11.31±3.31) and adrenals (9.65± 4.20/7.10±2.86). A comparison of pre- and post treatment values revealed no significant differences (P>0.05) in any of these organs. CONCLUSION: The uptake of [68Ga] DOTA-TOC in normal tissue is not significantly affected by PRRT. This is relevant with regards to therapeutic monitoring were tumor-to-non-tumor ratio seems to be the most robust biomarker.

[Chronic abdominal aortic graft infection : Detection with 18F-FDG-PET/CT]. / Chronischer zentraler Gefässprotheseninfekt : Nachweis durch (18)F-FDG-PET/CT.

A 67-year-old male patient presented with recurrent fever and septic emboli due to an aorto-duodenal fistula after previous aortobiiliac bypass grafting with suspected graft infection. Imaging by ultrasound, computed tomography scan (CT) and magnetic resonance imaging (MRI) could not confirm graft infection. A scan using 2-deoxy-2-fluoro-[18F]-d-glucose positron emission tomography CT (18F-FDG-PET/CT) revealed a pathological uptake. The bifurcated graft was removed und revascularization was performed by axillobifemoral bypass grafting. The clinical role of CT scanning with 18F-FDG-PET/CT is discussed including a review of the recent literature.