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A 76-year-old man with metastatic adenocarcinoma of the prostate presented with increasing dyspnea. After being treated initially with drainage and afterwards with pleurodesis, he was referred for Ga-prostate-specific membrane antigen 11 PET/CT imaging for restaging purposes. PET/CT demonstrated extensive Ga-prostate-specific membrane antigen 11 uptake in the right pleura. Histopathology confirmed the rare case of malignant pleural effusion from metastatic prostate cancer.

Dual-time point PET/CT scanning with [One hundred consecutive patients with biochemically recurrent PC who received standard and late [Seventy-nine of 100 patients had PSMA-positive scans, in whom a total of 185 individual PSMA-positive lesions were identified. These were morphologically characterised as bone lesions (n = 48), solid organ lesions (n = 3), lymph node (LN) lesions (n = 78) and locally recurrent lesions in the prostatic fossa or seminal vesicles (n = 56). The relative uptake between standard and late imaging was considered; all lesions classified as local recurrence presented with increasing (86%) or stable patterns of tracer uptake (14%). In contrast, only 58% of bone lesions exhibited increasing tracer uptake, with 21% exhibiting a stable pattern and 21% exhibiting a decreasing tracer uptake at late imaging.A heterogeneous pattern of dynamic tracer uptake was observed, with a largely increasing pattern observed for locally recurrent lesions and lymph nodes and a significant proportion of bone lesions exhibiting decreasing tracer uptake. The results are of significance not only in the imaging and identification of PC lesions, but they also have implications for PSMA-directed ligand therapy.

A patient with bone metastases of prostate cancer was referred for 68Ga-PSMA-11 PET/CT. Compared to a 68Ga-PSMA-11 PET/CT four months previously, the CT-component of the current PET/CT showed morphological progress in all lesions despite continuous therapy with docetaxel and denosumab. Contrarily, the PET-component showed a reduction of tracer-uptake, which correlated with PSA decrease between the two PET/CT-scans (16.2 ng/ml vs. 3.1 ng/ml). This case highlights 68Ga-PSMA-11 PET/CT as a promising tool for therapy monitoring of prostate cancer and could serve as a basis for a novel monitoring strategy. Volume progress shown by CT must not be classified as tumor progress, but as bone remodeling following effective therapy.

Recently introduced fluorine-18 prostate-specific membrane antigen-1007 (18F-PSMA-1007) for imaging prostate cancer has an intense physiologic liver uptake and biliary excretion. The aim of the present study was to evaluate the effect of different dietary conditions on this physiological uptake. Forty consecutive prostate cancer patients were scanned with 18F-PSMA-1007 positron emission tomography/computed tomography at different dietary conditions. In addition to a blinded read scoring, tracer uptake intensities (standardized uptake values [SUVs]) were measured in the liver and small bowel. There was no significant difference in liver and small-bowel uptake between different patient groups. Wilcoxon signed-rank tests revealed no significant difference of the median mean SUV of the liver or maximum SUV of the horizontal part of the duodenum between different dietary conditions groups. A dietary preparation of patients by fasting or the attempt to clear liver activity by high caloric drinks does not have a significant effect on tracer uptake in the liver or in the small bowel.

The emerging PSMA-targeted radionuclide therapy provides an effective method for the treatment of advanced metastatic prostate cancer. To optimize the therapeutic effect and maximize the theranostic benefit, there is a need to identify and quantify target lesions prior to treatment. However, this is extremely challenging considering that a high number of lesions of heterogeneous size and uptake may distribute in a variety of anatomical context with different backgrounds. This study proposes an end-to-end deep neural network to characterize the prostate cancer lesions on PSMA imaging automatically. A 68Ga-PSMA-11 PET/CT image dataset including 71 patients with metastatic prostate cancer was collected from three medical centres for training and evaluating the proposed network. For proof-of-concept, we focus on the detection of bone and lymph node lesions in the pelvic area suggestive for metastases of prostate cancer. The preliminary test on pelvic area confirms the potential of deep learning methods. Increasing the amount of training data may further enhance the performance of the proposed deep learning method.

Purpose: Prostate specific antigen persistence after radical prostatectomy is associated with adverse outcomes in patients with prostate cancer. We sought to define regions at risk for residual disease as well as the accuracy of prostate specific membrane antigen ligand positron emission tomography in patients with prostate specific antigen persistence. Materials and methods: At 6 participating centers a total of 191 patients who underwent 68Ga-prostate specific membrane antigen-11 positron emission tomography/computerized tomography or positron emission tomography/magnetic resonance imaging for persistently elevated postoperative prostate specific antigen (0.1 ng/ml or greater) were retrospectively included in study. The detection rate and the positive predictive value were determined. In 33 patients with additional prostate specific membrane antigen ligand positron emission tomography before prostatectomy we also determined the rate of positron emission tomography based persistence and recurrence. Results: Prostate specific membrane antigen ligand positron emission tomography localized prostate cancer in 130 of 191 patients (68%) with prostate specific antigen persistence at a median prostate specific antigen of 1.1 ng/ml. The detection rate significantly increased with prostate specific antigen (p

The positron emission tomography (PET) tracer 68Ga-PSMA-11, targeting the prostate-specific membrane antigen (PSMA), is rapidly excreted into the urinary tract. This leads to significant radioactivity in the bladder, which may limit the PET-detection of local recurrence (LR) of prostate cancer (PC) after radical prostatectomy (RP), developing in close proximity to the bladder. Here, we analyze if there is additional value of multi-parametric magnetic resonance imaging (mpMRI) compared to the 68Ga-PSMA-11-PET-component of PET/CT or PET/MRI to detect LR. One hundred and nineteen patients with biochemical recurrence after prior RP underwent both hybrid 68Ga-PSMA-11-PET/CTlow-dose (1 h p.i.) and -PET/MRI (2-3 h p.i.) including a mpMRI protocol of the prostatic bed. The comparison of both methods was restricted to the abdomen with focus on LR (McNemar). Bladder-LR distance and recurrence size were measured in axial T2w-TSE. A logistic regression was performed to determine the influence of these variables on detectability in 68Ga-PSMA-11-PET. Standardized-uptake-value (SUVmean) quantification of LR was performed. There were 93/119 patients that had at least one pathologic finding. In addition, 18/119 Patients (15.1%) were diagnosed with a LR in mpMRI of PET/MRI but only nine were PET-positive in PET/CT and PET/MRI. This mismatch was statistically significant (p = 0.004). Detection of LR using the PET-component was significantly influenced by proximity to the bladder (p = 0.028). The PET-pattern of LR-uptake was classified into three types (1): separated from bladder; (2): fuses with bladder, and (3): obliterated by bladder). The size of LRs did not affect PET-detectability (p = 0.84), mean size was 1.7 ± 0.69 cm long axis, 1.2 ± 0.46 cm short-axis. SUVmean in nine men was 8.7 ± 3.7 (PET/CT) and 7.0 ± 4.2 (PET/MRI) but could not be quantified in the remaining nine cases (obliterated by bladder). The present study demonstrates additional value of hybrid 68Ga-PSMA-11-PET/MRI by gaining complementary diagnostic information compared to the 68Ga-PSMA-11-PET/CTlow-dose for patients with LR of PC.

The prostate-specific membrane antigen (PSMA) has received increased consideration during the past few years as an excellent target for both imaging and therapy of prostate cancer. After many years of outstanding preclinical research, the first significant step forward in clinical use was achieved in 2008 with the first human experience with the small-molecule PSMA inhibitors 123I-MIP-1972 and 123I-MIP-1095. A clinical breakthrough followed in 2011 with 68Ga-PSMA-11 for PET imaging and 131I-MIP-1095 for endoradiotherapy of metastatic prostate cancer. Since then, PET/CT with 68Ga-PSMA-11 has rapidly spread worldwide, and endoradiotherapy with PSMA ligands has been conducted at increasing numbers of centers. 68Ga-PSMA-11 is currently the subject of multicenter studies in different countries. Since 2013, 131I-related PSMA therapy has been replaced by 177Lu-labeled ligands, such as PSMA-617, which is also the subject of multicenter studies. Alternative PSMA ligands for both imaging and therapy are available. Among them is 99mTc-MIP-1404, which has recently entered a phase 3 clinical trial. This article focuses on the highlights of the development and clinical application of PSMA ligands.

The purpose of this work was to evaluate the effect of androgen receptor (AR) inhibition on prostate-specific membrane antigen (PSMA) uptake imaged using 68Ga-PSMA-11 PET in a mouse xenograft model and in a patient with castration-sensitive prostate cancer. Methods: We imaged 3 groups of 4 mice bearing LNCaP-AR xenografts before and 7 d after treatment with ARN-509, orchiectomy, or control vehicle. Additionally, we imaged one patient with castration-sensitive prostate cancer before and 4 wk after treatment with androgen deprivation therapy (ADT). Uptake on pre- and posttreatment imaging was measured and compared. Results: PSMA uptake increased 1.5- to 2.0-fold in the xenograft mouse model after treatment with both orchiectomy and ARN-509 but not with vehicle. Patient imaging demonstrated a 7-fold increase in PSMA uptake after the initiation of ADT. Thirteen of 22 lesions in the imaged patient were visualized on PSMA PET only after treatment with ADT. Conclusion: Inhibition of the AR can increase PSMA expression in prostate cancer metastases and increase the number of lesions visualized using PSMA PET. The effect seen in cell and animal models can be recapitulated in humans. A better understanding of the temporal changes in PSMA expression is needed to leverage this effect for both improved diagnosis and improved therapy.

Prostate-specific membrane antigen (PSMA) is a promising target for imaging diagnostics and targeted radionuclide therapy (theranostics) of prostate cancer and its metastases. There is increasing evidence of encouraging response rates and a low toxicity profile of radioligand therapy (RLT) of metastatic castration-resistant prostate cancer using 177Lu-labeled PSMA ligands. In this article, we review the current status of diagnostics and therapy using radiolabeled PSMA ligands. We also suggest protocols for patient selection criteria and conduct of PSMA-based RLT. Challenges and opportunities of PSMA theranostics are discussed.

Purpose The introduction of ligands targeting prostate-specific membrane antigen (PSMA), especially 68Ga-PSMA-11, has changed the management of patients with prostate cancer (PCa). 18F-Labelled ligands can be produced in larger amounts and therefore can improve availability for a larger group of patients. The aim of this study was to evaluate the diagnostic performance of the recently introduced 18F-PSMA-1007 in patients with recurrent PCa. Methods This retrospective analysis included 100 consecutive patients with biochemical relapse (mean age 68.75 ± 7.6 years) referred for PSMA PET/CT. Whole-body PET/CT imaging (from the lower limbs to the skull) was performed in all patients 120 min after injection of 338 ± 44.31 MBq 18F-PSMA-1007. Prostatectomy, radiation beam therapy of the prostate bed and androgen-deprivation therapy had been performed in 92%, 45% and 27% of the patients, respectively. Radiation beam therapy of the prostate bed had been performed in addition to surgery in 38 patients (38%) and 10 patients (10%) had received all three therapy modalities. The probability of a 18F-PSMA-1007 PET/CT scan suggestive of pathology was compared with the Gleason score (GS) and PSA level. Results Of the 100 patients, 95 (95%) showed at least one pathological finding on 18F-PSMA-1007 PET/CT. The overall median PSA level was 1.34 ng/ml (range 0,04–41.3 ng/ml). The rates of pathological scans were 86%, 89%, 100% and 100% among patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and > 2.0 ng/ml, respectively. The median GS was 7 (range 5–10). The majority of patients (70) with a GS available had a score in the range 7–9. The rate of pathological scans in these patients was 93% (65/70). The median SUVmax values of the pathological findings were 10.25, 14.32, 13.16 and 28.87 in patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/ml, respectively. The median SUVmax in patients with a PSA level of >2.0 ng/ml was significantly higher than in all other PSA groups. Conclusion 18F-PSMA-1007 PET/CT can detect recurrent PCa in a high percentage of patients with biochemical relapse. The probability of a pathological 18F-PSMA-1007 PET/CT scan seems to be high even in patients with a low PSA level ≤0.5 ng/ml, and this may have a significant impact on the management of this relevant group of patients.

To prospectively compare diagnostic accuracies for detection of bone metastases bySixty-eight PCa patients with BCR participated in this prospective study. The patients underwentTen of the 68 patients were diagnosed with bone metastases. On a patient level, sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic analysis were, respectively, 0.80, 0.98-1.00 and 0.89-0.90 for

The aim of this study was to analyze the robustness and diagnostic value of different compartment models for dynamic 18F-FET PET in recurrent high-grade glioma (HGG). Dynamic 18F-FET PET data of patients with recurrent WHO grade III (n:7) and WHO grade IV (n: 9) tumors undergoing re-irradiation with carbon ions were analyzed by voxelwise fitting of the time-activity curves with a simplified and an extended one-tissue compartment model (1TCM) and a two-tissue compartment model (2TCM), respectively. A simulation study was conducted to assess robustness and precision of the 2TCM. Parameter maps showed enhanced detail on tumor substructure. Neglecting the blood volume VB in the 1TCM yields insufficient results. Parameter K1 from both 1TCM and 2TCM showed correlation with overall patient survival after carbon ion irradiation (p = 0.043 and 0.036, respectively). The 2TCM yields realistic estimates for tumor blood volume, which was found to be significantly higher in WHO IV compared to WHO III (p = 0.031). Simulations on the 2TCM showed that K1 yields good accuracy and robustness while k2 showed lowest stability of all parameters. The 1TCM provides the best compromise between parameter stability and model accuracy; however application of the 2TCM is still feasible and provides a more accurate representation of tracer-kinetics at the cost of reduced robustness. Detailed tracer kinetic analysis of 18F-FET PET with compartment models holds valuable information on tumor substructures and provides additional diagnostic and prognostic value.

Purpose: To prospectively compare diagnostic accuracies for detection of bone metastases by 68Ga-PSMA PET/CT, 18F-NaF PET/CT and diffusion-weighted MRI (DW 600-MRI) in prostate cancer (PCa) patients with biochemical recurrence (BCR). Methods: Sixty-eight PCa patients with BCR participated in this prospective study. The patients underwent 68Ga-PSMA PET/CT, a 18F-NaF PET/CT and a DW 600-MRI (performed in accordance with European Society of Urogenital Radiology guidelines, with b values of 0 and 600 s/mm 2). Bone lesions were categorized using a three-point scale (benign, malignant or equivocal for metastases) and a dichotomous scale (benign or metastatic) for each imaging modality by at least two experienced observers. A best valuable comparator was defined for each patient based on study-specific imaging, at least 12 months of clinical follow-up and any imaging prior to the study and during follow-up. Diagnostic performance was assessed using a sensitivity analysis where equivocal lesions were handled as non-metastatic and then as metastatic. Results: Ten of the 68 patients were diagnosed with bone metastases. On a patient level, sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic analysis were, respectively, 0.80, 0.98–1.00 and 0.89–0.90 for 68Ga-PSMA PET/CT (n = 68 patients); 0.90, 0.90–0.98 and 0.90–0.94 for 18NaF PET/CT (n = 67 patients); and 0.25–0.38, 0.87–0.92 and 0.59–0.62 for DW 600-MRI (n = 60 patients). The diagnostic performance of DW 600-MRI was significantly lower than that of 68Ga-PSMA PET/CT and 18NaF PET/CT for diagnosing bone metastases (p < 0.01), and no significant difference in the AUC was seen between 68Ga-PSMA PET/CT and 18NaF PET/CT (p = 0.65). Conclusion: 68Ga-PSMA PET/CT and 18F-NaF PET/CT showed comparable and high diagnostic accuracies for detecting bone metastases in PCa patients with BCR. Both methods performed significantly better than DW 600-MRI, which was inadequate for diagnosing bone metastases when conducted in accordance with European Society of Urogenital Radiology guidelines.

PURPOSE: Since the introduction of PSMA PET/CT with 68Ga-PSMA-11, this modality for imaging prostate cancer (PC) has spread worldwide. Preclinical studies have demonstrated that short-term androgen deprivation therapy (ADT) can significantly increase PSMA expression on PC cells. Additionally, retrospective clinical data in large patient cohorts suggest a positive association between ongoing ADT and a pathological PSMA PET/CT scan. The present evaluation was conducted to further analyse the influence of long-term ADT on PSMA PET/CT findings. METHODS: A retrospective analysis was performed of all 1,704 patients who underwent a 68Ga-PSMA-11 PET/CT scan at our institution from 2011 to 2017 to detect PC. Of 306 patients scanned at least twice, 10 had started and continued ADT with a continuous clinical response between the two PSMA PET/CT scans. These ten patients were included in the current analysis which compared the tracer uptake intensity and volume of PC lesions on PSMA PET/CT before and during ongoing ADT. RESULTS: Overall, 31 PC lesions were visible in all ten patients before initiation of ADT. However, during ongoing ADT (duration 42-369 days, median 230 days), only 14 lesions were visible in eight of the ten patients. The average tracer uptake values decreased in 71% and increased in 12.9% of the PC lesions. Of all lesions, 33.3% were still visible in six patients with a complete PSA response (≤0.1 ng/ml). CONCLUSION: Continuous long-term ADT significantly reduces the visibility of castration-sensitive PC on PSMA PET/CT. If the objective is visualization of the maximum possible extent of disease, we recommend referring patients for PSMA PET/CT before starting ADT. KEYWORDS: 68Ga-PSMA-11; Androgen deprivation therapy; PET/CT; PSMA; Prostate cancer; Prostate-specific membrane antigen

Owing to their superior uptake and higher detection rate, PSMA-labelled radioligands have largely replaced choline in routine clinical imaging of recurrent prostate cancer (PCa). Nevertheless, even at high PSA values, a small number of patients can present with PSMA negative prostate cancer (PC) lesions. For such patients choline PET continues to play an important role.

Purpose Radiotherapy is the main therapeutic approach besides surgery of localized prostate cancer. It relies on risk stratification and exact staging. This report analyses the potential of [68Ga]Glu-urea-Lys(Ahx)-HBED-CC (68Ga-PSMA-11), a new positron emission tomography (PET) tracer targeting prostate-specific membrane antigen (PSMA) for prostate cancer staging and individualized radiotherapy planning. Methods A cohort of 57 patients with prostate cancer scanned with 68Ga-PSMA-11 PET/CT for radiotherapy planning was retrospectively reviewed; 15 patients were at initial diagnosis and 42 patients at time of biochemical recurrence. Staging results of conventional imaging, including bone scintigraphy, CT or MRI, were compared with 68Ga-PSMA ligand PET/CT results and the influence on radiotherapeutic management was quantified. Results 68Ga-PSMA ligand PET/CT had a dramatic impact on radiotherapy application in the presented cohort. In 50.8 % of the cases therapy was changed. Conclusion The presented imaging technique of 68Ga-PSMA PET/CT could be a key technology for individualized radiotherapy management in prostate cancer.

Die PET/CT mit dem PSMA-Liganden 68Ga-PSMA-11 gilt als Durchbruch in der Diagnostik des rezidivierenden Prostatakarzinoms (PCa) und hat sich seit seiner klinischen Einfuhrung im Mai 2011 rasch national und international verbreitet. Die meisten PCa-Metastasen sind 3 h p. i. deutlicher zu sehen als in fruheren Aufnahmen. Die PSMA-Liganden PET/CT hat sich gegenuber der etablierten Cholin-PET/CT sowohl bei der Speicherintensitat als auch beim Kontrast der PCa-Herde v. a. bei niedrigen PSA-Werten und hohem Gleason-Score (GSC) als signifikant uberlegen gezeigt. Eine weitere Analyse bei 319 Patienten, bei denen eine PSMA-Liganden PET/CT durchgefuhrt wurde, ergab bei 82,8% zumindest einen PCa-typischen Befund. Die Wahrscheinlichkeit der Detektion von PCa-Herden stieg erwartungsgemas mit der PSA-Hohe. Unter einem PSA-Wert von 0,5 ng/ml betrug die Wahrscheinlichkeit, zumindest einen Tumorherd in der 68Ga-PSMA-Liganden PET/CT zu entdecken, ca. 50% und stieg mit der PSA-Hohe rasch an. Bei der Gesamtheit des Patientenkollektivs konnte bez. der Detektionswahrscheinlichkeit fur PCa-Herde kein signifikanter Unterschied zwischen hoheren und niedrigeren GSC festgestellt werden. Patienten mit laufender Androgen-Entzugstherapie (ADT) wiesen jedoch signifikant haufiger einen pathologischen Befund in der PSMA-Liganden PET/CT auf. Bei der patientenbasierten Analyse wurde eine Sensitivitat von 88,1% und bei der herd-basierten Analyse eine Sensitivitat, Spezifitat, negativer und positiver pradiktiver Werte von 76,6, 100, 91,4 und 100% berechnet. Bei 40% der nachbeobachteten Patienten wurde im Anschluss an die PSMA-Liganden PET/CT eine lokale anstatt einer systemischen Therapie durchgefuhrt. Der PSMA-Rezeptor eignet sich in hervorragender Weise auch fur eine Radioligandentherapie (sog. zielgerichtete Endoradiotherapie). Die ersten PSMA-Therapien, ebenfalls im Jahr 2011 eingefuhrt, erfolgten noch mit 131I-markierten Liganden. Die ersten Erfahrungen mit 28 Patienten zeigten nach einem einzigen Zyklus vielversprechende Ergebnisse: bei 60,7% der Patienten sank der PSA-Wert um mindestens 50%. In Dosimetrien konnten Herddosen von bis zu 300 Gy erreicht werden. Ferner zeigte sich eine lange Verweildauer des Therapieliganden in den Tumorherden. Seit 2013 werden nunmehr u. a. aufgrund der kurzeren stationaren Verweildauer 177Lu-markierte Therapieliganden, z. B. PSMA-617, eingesetzt.

Despite many advances in the past years, the treatment of metastatic prostate cancer still remains challenging. In recent years, prostate-specific membrane antigen (PSMA) inhibitors were intensively studied to develop low-molecular-weight ligands for imaging prostate cancer lesions by PET or SPECT. However, the endoradiotherapeutic use of these compounds requires optimization with regard to the radionuclide-chelating agent and the linker moiety between chelator and pharmacophore, which influence the overall pharmacokinetic properties of the resulting radioligand. In an effort to realize both detection and optimal treatment of prostate cancer, a tailor-made novel naphthyl-containing DOTA-conjugated PSMA inhibitor has been developed. Methods: The peptidomimetic structure was synthesized by solid-phase peptide chemistry and characterized using reversed-phase high-performance liquid chromatography and matrix-assisted laser desorption/ionization mass spectrometry. Subsequent 67/68Ga and 177Lu labeling resulted in radiochemical yields of greater than 97% or greater than 99%, respectively. Competitive binding and internalization experiments were performed using the PSMA-positive LNCaP cell line. The in vivo biodistribution and dynamic small-animal PET imaging studies were investigated in BALB/c nu/nu mice bearing LNCaP xenografts. Results: The chemically modified PSMA inhibitor PSMA-617 demonstrated high radiolytic stability for at least 72 h. A high inhibition potency (equilibrium dissociation constant [Ki] = 2.34 ± 2.94 nM on LNCaP; Ki = 0.37 ± 0.21 nM enzymatically determined) and highly efficient internalization into LNCaP cells were demonstrated. The small-animal PET measurements showed high tumor-to-background contrasts as early as 1 h after injection. Organ distribution revealed specific uptake in LNCaP tumors and in the kidneys 1 h after injection. With regard to therapeutic use, the compound exhibited a rapid clearance from the kidneys from 113.3 ± 24.4 at 1 h to 2.13 ± 1.36 percentage injected dose per gram at 24 h. The favorable pharmacokinetics of the molecule led to tumor-to-background ratios of 1,058 (tumor to blood) and 529 (tumor to muscle), respectively, 24 h after injection. Conclusion: The tailor-made DOTA-conjugated PSMA inhibitor PSMA-617 presented here is sustainably refined and advanced with respect to its tumor-targeting and pharmacokinetic properties by systematic chemical modification of the linker region. Therefore, this radiotracer is suitable for a first-in-human theranostic application and may help to improve the clinical management of prostate cancer in the future.

PURPOSE Since the introduction ofGa-PSMA-11 PET/CT for imaging prostate cancer (PC) we have frequently observed mediastinal lymph nodes (LN) showing tracer uptake despite being classified as benign. The aim of this evaluation was to further analyze such LN. METHODS Two patient groups with biphasicGa-PSMA-11 PET/CT at 1 h and 3 h p.i. were included in this retrospective evaluation. Group A (n = 38) included patients without LN metastases, and group B (n = 43) patients with LN metastases of PC. SUV of mediastinal/paraaortal LN of group A (n = 100) were compared to SUV of LN metastases of group B (n = 91). Additionally, 22 randomly selected mediastinal and paraaortal LN of patients without PC were immunohistochemically (IHC) analyzed for PSMA expression. RESULTS In group A, 7/38 patients (18.4%) presented with at least one PSMA-positive mediastinal LN at 1 h p.i. and 3/38 (7.9%) positive LN at 3 h p.i. with a SUVmax of 2.3 ± 0.7 at 1 h p.i. (2.0 ± 0.7 at 3 h p.i.). A total of 11 PSMA-positive mediastinal/paraaortal LN were detected in nine patients considering both imaging timing points. SUVmax of LN-metastases was 12.5 ± 13.2 at 1 h p.i. (15.8 ± 17.0 at 3 h p.i.). SUVmax increased clearly (> 10%) between 1 h and 3 h p.i. in 76.9% of the LN metastases, and decreased significantly in 72.7% of the mediastinal/paraaortal LN. By IHC, PSMA-expression was observed in intranodal vascular endothelia of all investigated LN groups and to differing degrees within germinal centers of 15/22 of them (68.1%). Expression was stronger in mediastinal nodes (p = 0.038) and when follicular hyperplasia was present (p = 0.050). CONCLUSION PSMA-positive mediastinal/paraaortal benign LN were visible in a notable proportion of patients. PSMA-positivity on the histopathological level was associated with the activation state of the LN. However, in contrast to LN metastases of PC, they presented with significantly lower uptake, which, in addition, usually decreased over time.

The objective of this study was to evaluate the rate of detection of bone metastases obtained with the prostate-specific membrane antigen (PSMA)-targeting tracer

The rapidly expanding clinical adaptation of prostate-specific membrane antigen (PSMA)-targeted PET imaging in the evaluation of patients with prostate cancer has placed an increasing onus on understanding both the potential pearls of interpretation as well as limitations of this new technique. As with any new molecular imaging modality, accurate characterization of abnormalities on PSMA-targeted PET imaging can be accomplished only if one is aware of the normal distribution pattern, physiological variants of radiotracer uptake, and potential sources of false-positive and false-negative imaging findings. In recent years, a growing number of reports have come to light describing incidental non-prostatic benign or malignant pathologies with high uptake on PSMA-targeted PET imaging. In this review, we have summarized the published literature regarding the potential pearls and technical and interpretive pitfalls of this imaging modality. Knowledge of these limitations can increase the confidence of interpreting physicians and thus improve patient care. As PSMA-targeted PET is expected to be evaluated in larger prospective trials, the dissemination of potential diagnostic pitfalls and the biologic underpinning of those findings will be of increased importance.

PSMA ligand imaging with hybrid PET/MRI scanners could be an integral part of the clinical routine in the future. However, the first study about this novel method revealed a severe photopenic artifact ("halo artifact") around the urinary bladder causing significantly reduced tumor visibility. The aim of this evaluation was to analyze the role of arm truncation on the appearance of the halo artifact inTwenty-seven consecutive patients were subjected toThe halo was significantly reduced if the arms were elevated. Lesions inside the halo artifact (n = 16) demonstrated significantly increased SUVmean (p = 0.0007) and SUVmax (p = 0.0024) with arms positioned up. The halo appearance and intensity was not dependent on the total activity and activity concentration of the urinary bladder.Positioning the arms down was shown to be significantly associated with the appearance of the halo artifact in PET/MRI. Positioning the arms up above the head can significantly reduce the halo artifact, thereby detecting more tumor lesions.

Targeting the prostate-specific membrane antigen (PSMA) with 68Ga-labeled and 18F-labeled PET agents has become increasingly important in recent years. Imaging of biochemically recurrent prostate cancer has been established as a widely accepted clinical indication for PSMA ligand PET/CT in many parts of the world because of the results of multiple, primarily retrospective, studies that indicate superior detection efficacy compared with standard-of-care imaging. For high-risk primary prostate cancer, evidence is growing that this modality significantly aids in the detection of otherwise occult nodal and bone metastases. For both clinical indications in recurrent as well as in primary prostate cancer, preliminary data demonstrate a substantial impact on clinical management. Emerging data imply that intraprostatic tumor localization, therapy stratification, and treatment monitoring of advanced disease in specific clinical situations might become future indications. Current criteria for image reporting of PSMA ligand PET are evolving given the expanding body of literature on physiologic and pathologic uptake patterns and pitfalls. This article intends to give an educational overview on the current status of PSMA ligand PET imaging, including imaging procedure and interpretation, clinical indications, diagnostic potential, and impact on treatment planning.

68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT represents an advanced method for the staging of primary prostate cancer (PCa) and diagnosis of recurrent or metastatic PCa. However, because of the narrow availability of 68Ga the development of alternative tracers is of high interest. The objective of this study was to examine the value of the new PET tracer 18F-PSMA-1007 for the staging of local disease by comparing it with multiparametric MRI (mpMRI) and radical prostatectomy (RP) histopathology. Methods: In 2016, 18F-PSMA-1007 PET/CT was performed in 10 men with biopsy-confirmed high-risk PCa. Nine patients underwent mpMRI in the process of primary diagnosis. Consecutively, RP was performed in all 10 men. Agreement analysis was performed retrospectively. PSMA staining was added for representative sections in RP specimen slices. Localization and agreement analysis of 18F-PSMA-1007 PET/CT, mpMRI, and RP specimens was performed by dividing the prostate into 38 sections as described in the prostate imaging reporting and data system (PI-RADS) (version 2). Sensitivity, specificity, positive predictive values, negative predictive values (NPVs), and accuracy were calculated for total and near-total agreement. Results:18F-PSMA-1007 PET/CT had an NPV of 68% and an accuracy of 75%, and mpMRI had an NPV of 88% and an accuracy of 73% for total agreement. Near-total agreement analysis resulted in an NPV of 91% and an accuracy of 93% for 18F-PSMA-1007 PET/CT and 91% and 87% for mpMRI, respectively. Retrospective combination of mpMRI and PET/CT had an accuracy of 81% for total and 93% for near-total agreement. Conclusion: Comparison with RP histopathology demonstrates that 18F-PSMA-1007 PET/CT is promising for accurate local staging of PCa.

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.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).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 of16.4 for SUVmax, the sensitivity and specificity in predicting responding lesions were 95 and 60 %, respectively.We propose a SUVmax cutoff of16.4 from [(68)Ga]DOTATOC-PET-CT to select patients for PRRT. A T/L ratio2.2 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.

(68)Ga-DOTATOC-PET/CT is a well-established method for detecting and targeting the volume definition of meningiomas prior to radiotherapy. Moreover, there is evidence that this method is able to detect meningiomas with higher sensitivity than the goldstandard MRI. Since the hybrid PET/MRI scanner became available in the past few years, the next stage of development could consequently evolve by evaluating the feasibility of a hybrid PET/MRI scanner using (68)Ga-DOTATOC for detecting meningiomas.Fifteen patients received (68)Ga-DOTATOC-PET/CT (0.5 h post injection [p.i.]) followed by PET/MRI 2 hours p.i. Both investigations were analyzed separately and then compared with respect to image quality, detection of intracranial meningiomas, and radiotracer uptake values (RUVs). In addition, ratios between radiotracer uptake in meningiomas and pituitary glands were compared between both PET/CT and PET/MRI.Overall, 33 intracranial meningiomas were detected. All were visible with high contrast in both PET/CT and PET/MRI. (68)Ga-DOTATOC-PET/MRI provided flawless image quality without artefacts. Calculated RUV in meningiomas, as well as the ratios of RUVs in meningiomas to those of pituitary glands, were higher in PET/CT. As a result, meningiomas can be distinguished from pituitary glands better in early images.(68)Ga-DOTATOC-PET/MRI provided flawless image quality and presented an ideal combination of high sensitivity/specificity (PET) and the best possible morphological visualization of meningiomas (MRI). In addition, excellent detection of meningiomas is already possible at 0.5 hours p.i. Later images do not improve the distinction between pituitary gland and adjacent meningiomas. However, RUVs need to be carefully compared between both imaging modalities.

Introduction Since the prostate-specific membrane antigen (PSMA) is frequently over-expressed in prostate cancer (PCa) several PSMA-targeting molecules are under development to detect and treat metastatic castration resistant prostate cancer (mCRPC). We investigated the tissue kinetics of a small molecule inhibitor of PSMA ((S)-2-(3-((S)-1-carboxy-5-(3-(4-[124I]iodophenyl)ureido)pentyl)ureido)pentanedioicacid; MIP-1095) using PET/CT to estimate radiation dosimetry for the potential therapeutic use of 131I-MIP-1095 in men with mCRPC. We also report preliminary safety and efficacy of the first 28 consecutive patients treated under a compassionate-use protocol with a single cycle of 131I-MIP-1095. Methods Sixteen patients with known prostate cancer underwent PET/CT imaging after i.v. administration of 124I-MIP-1095 (mean activity: 67.4 MBq). Each patient was scanned using PET/CT up to five times at 1, 4, 24, 48 and 72 h post injection. Volumes of interest were defined for tumor lesions and normal organs at each time point followed by dose calculations using the OLINDA/EXM software. Twenty-eight men with mCRPC were treated with a single cycle of 131I-MIP-1095 (mean activity: 4.8 GBq, range 2 to 7.2 GBq) and followed for safety and efficacy. Baseline and follow up examinations included a complete blood count, liver and kidney function tests, and measurement of serum PSA. Results I-124-MIP-1095 PET/CT images showed excellent tumor uptake and moderate uptake in liver, proximal intestine and within a few hours post-injection also in the kidneys. High uptake values were observed only in salivary and lacrimal glands. Dosimetry estimates for I-131-MIP-1095 revealed that the highest absorbed doses were delivered to the salivary glands (3.8 mSv/MBq, liver (1.7 mSv/MBq) and kidneys (1.4 mSv/MBq). The absorbed dose calculated for the red marrow was 0.37 mSv/MBq. PSA values decreased by >50 % in 60.7 % of the men treated. Of men with bone pain, 84.6 % showed complete or moderate reduction in pain. Hematological toxicities were mild. Of men treated, 25 % had a transient slight to moderate dry mouth. No adverse effects on renal function were observed. Conclusion Based on the biodistribution and dose calculations of the PSMA-targeted small molecule 124I-MIP-1095 therapy with the authentic analog 131I-MIP-1095 enables a targeted tumor therapy with unprecedented doses delivered to the tumor lesions. Involved lymph node and bone metastases were exposed to estimated absorbed doses upwards of 300 Gy. Electronic supplementary material The online version of this article (doi:10.1007/s00259-014-2713-y) contains supplementary material, which is available to authorized users.

weitere Verfasser ausserhalb der UDE

Radiolabeled amino acids for single photon emission computed tomography (SPECT) and positron emission tomography (PET) have been under evaluation for several decades.1,2 However, gamma emitting tracers such as 123I-iodo-alpha-methyl-tyrosine, suffer from the limited resolution and low signal-to-noise ratio of the current SPECT technique.3,4 The first frequently used amino acid for PET was 11C-methionine (MET), but the short half-life of 11C (20 min) limited its application to centers with an on-site cyclotron.2 Therefore, 18F-labeled tracers have been introduced to provide both high resolution and practicable half-life (110 min) for routine applications.5,6 One of them, L-3,4-dihydroxy-6-18F-fluoro-phenyl-alanine (18F-DOPA), was found to be a multitargeted molecule.7 As a precursor of dopamine, it was used to trace the dopaminergic pathway in the nigrostriatal region to evaluate the presynaptic function in patients with neurodegenerative and movement disorders. Another common indication has been the evaluation of neuroendocrine tumors that present with the ability to take up amino acids and transform them into biogenic amines such as noradrenaline (pheochromocytoma) or serotonin (carcinoids) by decarboxylation (APUD tumors, “amine precursor uptake and decarboxylation”). 18F-DOPA also demonstrated the ability to distinguish between the diffuse and focal types of congenital hyperinsulinemia.7 Finally, 18F-DOPA is a substrate to the large neutral amino acid transport system that is highly expressed in primary brain tumors.8 In 2009, 18F-DOPA was approved in Europe for evaluation of recurrent brain tumors, as documented in the official product insert, and is now routinely used in our institution.9 O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) emerged in the same time frame as a promising PET tracer for brain tumors, and its scientific applications are growing rapidly because of its efficient radiosynthesis.10,11,12 However, no explicit side-by-side comparison of these 2 18F-labeled amino acid analogs has been performed until now. The present analysis evaluates 18F-FET and 18F-DOPA for glial brain tumors to compare their kinetics, correlation with tumor grading, and impact upon target tissue delineation when planning radiation treatment.

Purpose Positron emission tomography (PET) with choline tracers has found widespread use for the diagnosis of prostate cancer (PC). However, choline metabolism is not increased in a considerable number of cases, whereas prostate-specific membrane antigen (PSMA) is overexpressed in most PCs. Therefore, a 68Ga-labelled PSMA ligand could be superior to choline tracers by obtaining a high contrast. The aim of this study was to compare such a novel tracer with standard choline-based PET/CT. Methods Thirty-seven patients with biochemical relapse of PC [mean prostate-specific antigen (PSA) 11.1 ± 24.1 ng/ml, range 0.01–116] were retrospectively analysed after 18F-fluoromethylcholine and 68Ga-PSMA PET/CT within a time window of 30 days. Radiotracer uptake that was visually considered as PC was semi-quantitatively analysed by measuring the maximum standardized uptake values (SUVmax) of the scans acquired 1 h after injection of 68Ga-PSMA complex solution (median 132 MBq, range 59–263 MBq) and 18F-fluoromethylcholine (median 237 MBq, range 114–374 MBq), respectively. In addition, tumour to background ratios were calculated. Results A total of 78 lesions characteristic for PC were detected in 32 patients using 68Ga-PSMA PET/CT and 56 lesions were detected in 26 patients using choline PET/CT. The higher detection rate in 68Ga-PSMA PET/CT was statistically significant (p = 0.04). In five patients no lesion was found with both methods. All lesions detected by 18F-fluoromethylcholine PET/CT were also seen by 68Ga-PSMA PET/CT. In 68Ga-PSMA PET/CT SUVmax was clearly (>10 %) higher in 62 of 78 lesions (79.1 %) and the tumour to background ratio was clearly (>10 %) higher in 74 of 78 lesions (94.9 %) when compared to 18F-fluoromethylcholine PET/CT. Conclusion 68Ga-PSMA PET/CT can detect lesions characteristic for PC with improved contrast when compared to standard 18F-fluoromethylcholine PET/CT, especially at low PSA levels. Electronic supplementary material The online version of this article (doi:10.1007/s00259-013-2525-5) contains supplementary material, which is available to authorized users.

Das Ziel besteht in der Verbesserung der Detektion und Staging des Prostatakarzinoms mittels innovativer Bildgebungstechnik wie PET/MRT. Die Modalitat der Wahl zur Detektion des Prostatakarzinoms ist die multiparametrische MRT. Des Weiteren wird die PET/CT insbesondere zum Staging und zur Detektion von Fernmetastasten/Rezidivdiagnostik eingesetzt. Zur Darstellung von Knochenmetastasen ist das am haufigsten eingesetzte Verfahren die Szintigraphie. Die Entwicklung einer simultanen, hybriden PET/MRT stellt die letzte grose „Vereinigung“ der bekannten Schnittbildmodalitaten dar. Zusatzlich ermoglicht die Synthese von neuen innovativen Tracern wie 18F-FACBC und 68Ga-PSMA (PSMA prostataspezifisches Membranantigen) spezifischere Detektion des Prostatakarzinoms. Die hybride PET/MRT-Bildgebung hat das Potenzial, in der Zukunft konventionelle Techniken abzulosen. Das Verfahren steht erst am Anfang der breiten Anwendung. Die Studienlage muss ausgebaut werden, um den zusatzlichen Nutzen zu belegen. Aktuell besteht noch eine geringe Verbreitungslage, da es sich um ein neues und kostenintensives Verfahren handelt. Zugleich existiert noch keine einheitliche Losung des Kostenersatzes durch die Kassen. Die Bedeutung fur die Praxis steigt erst mit Klarung der Vergutungssituation und Beleg des Nutzens durch grosere Studien.

The positron emission tomography (PET) tracerOne hundred and nineteen patients with biochemical recurrence after prior RP underwent both hybridThere were 93/119 patients that had at least one pathologic finding. In addition, 18/119 Patients (15.1%) were diagnosed with a LR in mpMRI of PET/MRI but only nine were PET-positive in PET/CT and PET/MRI. This mismatch was statistically significant (p = 0.004). Detection of LR using the PET-component was significantly influenced by proximity to the bladder (p = 0.028). The PET-pattern of LR-uptake was classified into three types (1): separated from bladder; (2): fuses with bladder, and (3): obliterated by bladder). The size of LRs did not affect PET-detectability (p = 0.84), mean size was 1.7 ± 0.69 cm long axis, 1.2 ± 0.46 cm short-axis. SUVThe present study demonstrates additional value of hybrid

Although PET/CT with

The prostate-specific membrane antigen (PSMA) is expressed by approximately 90% of prostate carcinomas. The expression correlates with unfavorable prognostic factors, such as a high Gleason score, infiltrative growth, metastasis, and hormone-independence. The high specificity, especially in the undifferentiated stage, makes it an excellent target for diagnosis and therapy. Therefore, antibodies and small molecule inhibitors have been developed for imaging and therapy. In 2011 PSMA-11, a ligand that consists of the Glu-urea-motif and the chelator HBED-CC, which can be exclusively radiolabeled with 68 Ga for PET imaging, presented the clinical breakthrough for prostate cancer diagnostics. In two large diagnostic studies ( n = 319 and n = 248) PET/CT with PSMA-11 successfully localized the recurrent tumor in approximately 90% of patients with biochemical relapse. Integrating PSMA-PET/CT into the planning phase of radiotherapy, the treatment concept is changed in 30%-50% of the patients. The combination of the Glu-urea-motif with DOTA, which can be labeled with several diagnostic and therapeutic radionuclides, opened new avenues for therapeutic usage of the small-molecule PSMA ligands. In the beginning of 2016, there are four confirmative reports ( n = 19, n = 24, n = 30, and n = 56) from four different centers reporting a PSA response in approximately 70% of patients treated with 177 Lu-labeled PSMA ligands. In conclusion, the data available up to now indicate a widespread use of PSMA ligands for diagnostic applications with respect to staging, detection of recurrence, or metastases in patients with rising tumor markers and for therapy in case of failure of guideline-compliant treatment.

The clinical introduction of (68)Ga-PSMA-11 ("HBED-CC") ligand targeting the prostate-specific membrane antigen (PSMA) has been regarded as a significant step forward in the diagnosis of prostate cancer (PCa). In this study, we provide human dosimetry and data on optimal timing of PET imaging after injection.Four patients with recurrent PCa were referred for (68)Ga-PSMA-11 PET/CT. Whole-body PET/CTlow-dose scans were conducted at 5 min, and 1, 2, 3, 4 and 5 h after injection of 152-198 MBq (68)Ga-PSMA-11. Organs of moderate to high uptake were used as source organs; their total activity was determined at all measured time points. Time-activity curves were created for each source organ as well as for the remainder. The radiation exposure of a (68)Ga-PSMA-11 PET was identified using the OLINDA-EXM software. In addition, tracer uptake was measured in 16 sites of metastases.The highest tracer uptake was observed in the kidneys, liver, upper large intestine, and the urinary bladder. Mean organ doses were: kidneys 0.262 ± 0.098 mGy/MBq, liver 0.031 ± 0.004 mGy/MBq, upper large intestine 0.054 ± 0.041 mGy/MBq, urinary bladder 0.13 ± 0.059 mGy/MBq. The calculated mean effective dose was 0.023 ± 0.004 mSv/MBq (=0.085 ± 0.015 rem/mCi). Most tumor lesions (n = 16) were visible at 3 h p.i., while at all other time points many were not qualitatively present (10/16 visible at 1 h p.i.).The mean effective dose of a (68)Ga-PSMA-11 PET is 0.023 mSv/MBq. A 3-h delay after injection was optimal timing for (68)Ga-PSMA-11 PET/CT in this patient cohort.

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 68Ga, 99mTc and 123/124/131I. Our initial experience with Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)](68Ga-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.

PET imaging with somatostatin receptor ligands, such as 68Ga-DOTATOC, is a well-established method for detection and target volume definition of meningiomas prior to radiotherapy. Since DOTATOC PET delivers a higher contrast between meningiomas and surrounding tissues than MRI, we conducted a retrospective analysis to compare the diagnostic accuracy of contrast-enhanced MRI (CE-MRI) with 68Ga-DOTATOC PET/CT in patients with cranial meningiomas prior to radiotherapy. Over a period of 6 years, 134 patients (20–82 years of age, 107 women and 27 men) underwent cranial CE-MRI and 68Ga-DOTATOC PET/CT. To compare the two methods, the lesions considered typical of meningiomas visually were counted and analysed with respect to their location and SUVmax. In the 134 patients investigated by both modalities, 190 meningiomas were detected by 68Ga-DOTATOC PET/CT and 171 by CE-MRI. With knowledge of the PET/CT data, the MRI scans were reinvestigated, which led to the detection of 4 of the 19 incidental meningiomas, resulting in an overall detection rate of 92 % of the meningioma lesions that were found by PET/CT. Ga-DOTATOC PET/CT demonstrated an improved sensitivity in meningioma detection when compared to CE-MRI. Tumours adjacent to the falx cerebri, located at the skull base or obscured by imaging artefacts or calcification are particularly difficult to detect by MRI. Therefore 68Ga-DOTATOC PET/CT may provide additional information in patients with uncertain or equivocal results on MRI or could help to confirm a diagnosis of meningioma based on MRI or could help to confirm MRI-based diagnosis of meningiomas in cases of biopsy limitations. It is possible that not only radiotherapy and surgical planning, but also follow-up strategies would benefit from this imaging modality.

Klinisches/methodisches Problem Konventionelle Methoden des Stagings, Therapiemonitorings und -Kontrolle bei Lymphomerkrankungen basieren auf morphologische Veranderungen, in der Regel dem Lasionsdurchmesser. Hierbei ist jedoch eine Vitalitat des Tumors in diesen Herden nicht evaluierbar.

Prostate-specific membrane antigen (PSMA) is an excellent target for radionuclide therapy of metastasized castration-resistant prostate cancer (mCRPC). Besides high affinity and long tumor retention, the DOTA-conjugated ligand PSMA-617 has low kidney uptake, making it an excellent choice for therapeutic application. We retrospectively report our experience with (177)Lu-PSMA-617-targeted radionuclide therapy in a case series of mCRPC patients resistant to other treatments.Patients with PSMA-positive tumor phenotypes were selected by molecular imaging. Thirty patients received 1-3 cycles of (177)Lu-PSMA-617. During therapy, pharmacokinetics and radiation dosimetry were evaluated. Blood cell count was checked every 2 wk after the first and every 4 wk after succeeding cycles. Prostate-specific antigen (PSA) was determined every 4 wk. Radiologic restaging was performed after 3 cycles.Twenty-one of 30 patients had a PSA response; in 13 of 30 the PSA decreased more than 50%. After 3 cycles, 8 of 11 patients achieved a sustained PSA response (50%) for over 24 wk, which also correlated with radiologic response (decreased lesion number and size). Normally, acute hematotoxicity was mild. Diffuse bone marrow involvement was a risk factor for higher grade myelosuppression but could be identified by PSMA imaging in advance. Xerostomia, nausea, and fatigue occurred sporadically (10%). Clearance of non-tumor-bound tracer was predominantly renal and widely completed by 48 h. Safety dosimetry revealed kidney doses of approximately 0.75 Gy/GBq, red marrow doses of 0.03 Gy/GBq, and salivary gland doses of 1.4 Gy/GBq, irrespective of tumor burden and consistent on subsequent cycles. Mean tumor-absorbed dose ranged from 6 to 22 Gy/GBq during cycle 1.(177)Lu-PSMA-617 is a promising new option for therapy of mCRPC and deserves more attention in larger prospective trials.

To evaluate the reproducibility of the combination of hybrid PET/MRI and the 68Ga-PSMA-11 tracer in depicting lymph node (LN) and bone metastases of prostate cancer (PC) in comparison with that of PET/CT. A retrospective analysis of 26 patients who were subjected to 68Ga-PSMA PET/CTlow-dose (1 h after injection) followed by PET/MRI (3 h after injection) was performed. MRI sequences included T1-w native, T1-w contrast-enhanced, T2-w fat-saturated and diffusion-weighted sequences (DWIb800). Discordant PET-positive and morphological findings were evaluated. Standardized uptake values (SUV) of PET-positive LNs and bone lesions were quantified and their morphological size and conspicuity determined. Comparing the PET components, the proportion of discordant PSMA-positive suspicious findings was very low (98.5 % of 64 LNs concordant, 100 % of 28 bone lesions concordant). Two PET-positive bone metastases could not be confirmed morphologically using CTlow-dose, but could be confirmed using MRI. In 12 of 20 patients, 47 PET-positive LNs (71.9 %) were smaller than 1 cm in short axis diameter. There were significant linear correlations between PET/MRI SUVs and PET/CT SUVs in the 64 LN metastases (p

PET imaging with the prostate-specific membrane antigen (PSMA)–targeted radioligand 68Ga-PSMA-11 is regarded as a significant step forward in the diagnosis of prostate cancer (PCa). More recently, a PSMA ligand was developed that can be labeled with 68Ga, 111In, 177Lu, and 90Y. This ligand, named PSMA-617, therefore enables both diagnosis and therapy of PCa. The aims of this evaluation were to clinically investigate the distribution of 68Ga-PSMA-617 in normal tissues and in PCa lesions as well as to evaluate the radiation exposure by the radioligand in PET imaging. Methods: Nineteen patients, most of them with recurrent PCa, were referred for 68Ga-PSMA-617 PET/CT. The quantitative assessment of tracer uptake of several organs and of 53 representative tumor lesions was performed in 15 patients at 1 and 3 h after injection. In 4 additional patients, the same procedure was conducted at 5 min, 1 h, 2 h, 3 h, 4 h, and 5 h after injection. On the basis of the data for these 4 patients (mean injected dose, 231 MBq), the radiation exposure of a 68Ga-PSMA-617 PET/CT was identified. Results: Intense tracer uptake was observed in the kidneys and salivary glands. In 14 of 19 patients (73.7%), at least 1 lesion suspected of being a tumor was detected at 3 h after injection. Of 53 representative tumor lesions selected at 3 h after injection, 47 lesions were visible at 1 h after injection. The mean tumor-to-background ratio for maximum standardized uptake value was 20.4 ± 17.3 (range, 2.3–84.0) at 1 h after injection and 38.2 ± 38.6 (range, 3.6–154.3) at 3 h after injection. The average radiation exposure (effective dose) was approximately 0.021 mSv/MBq. Conclusion: Within healthy organs, the kidneys and salivary glands showed the highest 68Ga-PSMA-617 uptake. The radiation exposure was relatively low. 68Ga-PSMA-617 shows PCa lesions with high contrast. Images obtained between 2 and 3 h after injection seem to be the best option with regard to radiotracer uptake and tumor contrast. Later images can help to clarify unclear lesions.

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)-[68Ga(HBED-CC)] (68Ga-PSMA-11) in the setting of recurrent prostate cancer. Methods All PET/CT images were acquired 60 ± 10 min after intravenous injection of 68Ga-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 68Ga-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 68Ga-PSMA-11 PET/CT detected nodal recurrence in two-thirds of patients who would have been missed using conventional morphological criteria. Conclusion 68Ga-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.