<Superscript>68</Superscript>Ga-PSMA PET/CT in patients with recurrent prostate cancer after radical treatment: prospective results in 314 patients

Purpose

We studied the usefulness of ⁶⁸Ga-prostate-specific membrane antigen (PSMA) PET/CT for detecting relapse in a prospective series of patients with biochemical recurrence (BCR) of prostate cancer (PCa) after radical treatment.

Methods

Patients with BCR of PCa after radical surgery and/or radiotherapy with or without androgen-deprivation therapy were included in the study. ⁶⁸Ga-PSMA PET/CT scans performed from the top of the head to the mid-thigh 60 min after intravenous injection of 150?±?50 MBq of ⁶⁸Ga-PSMA were interpreted by two nuclear medicine physicians. The results were correlated with prostate-specific antigen (PSA) levels at the time of the scan (PSApet), PSA doubling time, Gleason score, tumour stage, postsurgery tumour residue, time from primary therapy to BCR, and patient age. When available, ⁶⁸Ga-PSMA PET/CT scans were compared with negative ¹⁸F-choline PET/CT scans routinely performed up to 1 month previously.

Results

From November 2015 to October 2017, 314 PCa patients with BCR were evaluated. Their median age was 70 years (range 44–92 years) and their median PSApet was 0.83 ng/ml (range 0.003–80.0 ng/ml). ⁶⁸Ga-PSMA PET/CT was positive (one or more suspected PCa lesions detected) in 197 patients (62.7%). Lesions limited to the pelvis, i.e. the prostate/prostate bed and/or pelvic lymph nodes (LNs), were detected in 117 patients (59.4%). At least one distant lesion (LNs, bone, other organs, separately or combined with local lesions) was detected in 80 patients (40.6%). PSApet was higher in PET-positive than in PET-negative patients (P?<?0.0001). Of 88 patients negative on choline PET/CT scans, 59 (67%) were positive on ⁶⁸Ga-PSMA PET/CT.

Conclusion

We confirmed the value of ⁶⁸Ga-PSMA PET/CT in restaging PCa patients with BCR, highlighting its superior performance and safety compared with choline PET/CT. Higher PSApet was associated with a higher relapse detection rate.

     

Prospective comparison of <Superscript>68</Superscript>Ga-PSMA PET/CT, <Superscript>18</Superscript>F-sodium fluoride PET/CT and diffusion weighted-MRI at for the detection of bone metastases in biochemically recurrent prostate cancer

Purpose

To prospectively compare diagnostic accuracies for detection of bone metastases by ⁶⁸Ga-PSMA PET/CT, ¹⁸F-NaF PET/CT and diffusion-weighted MRI (DW₆₀₀-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 DW₆₀₀-MRI (performed in accordance with European Society of Urogenital Radiology guidelines, with b values of 0 and 600 s/mm²). 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 DW₆₀₀-MRI (n?=?60 patients). The diagnostic performance of DW₆₀₀-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 DW₆₀₀-MRI, which was inadequate for diagnosing bone metastases when conducted in accordance with European Society of Urogenital Radiology guidelines.

     

Review of commonly used prostate specific PET tracers used in prostate cancer imaging in current clinical practice

¹⁸F-Fluorodeoxyglucose positron emission tomography (FDG-PET) underperforms in detecting prostate cancer (PCa) due to inherent characteristics of primary and metastatic tumors, including relatively low rate of glucose utilization. Consequently, alternate PCa PET imaging agents targeting other aspects of PCa cell biology have been developed for clinical practice. The most common dedicated PET imaging tracers include ⁶⁸Ga/¹⁸F prostate-specific membrane antigen (PSMA), ¹¹C-Choline, and ¹⁸F-fluciclovine (Axumin™). This review will describe how these agents target specific inherent characteristics of PCa and explore the current literature for these agents for both primary and recurrent PCa, comparing the advantages and limitations of each tracer.Both ¹¹C-Choline and ¹⁸F-Fluciclovine PET have been shown to detect nodal and osseous disease at higher rates compared to FDG-PET but offer no additional benefit in detecting prostate disease, especially in primary staging. As a result, PSMA PET, specifically ⁶⁸Ga-PSMA-11, has emerged as a key imaging option for both primary and recurrent cancer. PSMA PET may be more sensitive than MRI at the local level and more sensitive than ¹¹C-Choline and ¹⁸F-Fluciclovine PET for distant disease. Furthermore, compared to ¹¹C-Choline and ¹⁸F-Fluciclovine PET, ⁶⁸Ga-PSMA-11 PET has higher detection rates at low PSA levels (<2 ng/dL). With improved delineation of disease, PSMA imaging has influenced treatment planning; radiation fields can be narrowed, and patients with isolated or oligo-metastatic disease can be spared systemic therapy. The retrospective nature of many of the studies describing these PCa imaging modalities complicates their assessment and comparison.     

MRI versus <Superscript>68</Superscript>Ga-PSMA PET/CT for gross tumour volume delineation in radiation treatment planning of primary prostate cancer

Purpose

Multiparametric magnetic resonance imaging (mpMRI) is widely used in radiation treatment planning of primary prostate cancer (PCA). Focal dose escalation to the dominant intraprostatic lesions (DIPL) may lead to improved PCA control. Prostate-specific membrane antigen (PSMA) is overexpressed in most PCAs. ⁶⁸Ga-labelled PSMA inhibitors have demonstrated promising results in detection of PCA with PET/CT. The aim of this study was to compare ⁶⁸Ga-PSMA PET/CT with MRI for gross tumour volume (GTV) definition in primary PCA.

Methods

This retrospective study included 22 patients with primary PCA analysed after ⁶⁸Ga-PSMA PET/CT and mpMRI. GTVs were delineated on MR images by two radiologists (GTV-MRIrad) and two radiation oncologists separately. Both volumes were merged leading to GTV-MRIint. GTVs based on PET/CT were delineated by two nuclear medicine physicians in consensus (GTV-PET). Laterality (left, right, and left and right prostate lobes) on mpMRI, PET/CT and pathological analysis after biopsy were assessed.

Results

Mean GTV-MRIrad, GTV-MRIint and GTV-PET were 5.92, 3.83 and 11.41 cm³, respectively. GTV-PET was significant larger then GTV-MRIint (p?=?0.003). The MRI GTVs GTV-MRIrad and GTV-MRIint showed, respectively, 40 % and 57 % overlap with GTV-PET. GTV-MRIrad and GTV-MRIint included the SUVmax of GTV-PET in 12 and 11 patients (54.6 % and 50 %), respectively. In nine patients (47 %), laterality on mpMRI, PET/CT and histopathology after biopsy was similar.

Conclusion

Ga-PSMA PET/CT and mpMRI provided concordant results for delineation of the DIPL in 47 % of patients (40 % – 54 % of lesions). GTV-PET was significantly larger than GTV-MRIint. ⁶⁸Ga-PSMA PET/CT may have a role in radiation treatment planning for focal radiation to the DIPL. Exact correlation of PET and MRI images with histopathology is needed.

     

<Superscript>68</Superscript>Ga-PSMA PET/CT: Joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0

The aim of this guideline is to provide standards for the recommendation, performance, interpretation and reporting of ⁶⁸Ga-PSMA PET/CT for prostate cancer imaging. These recommendations will help to improve accuracy, precision, and repeatability of ⁶⁸Ga-PSMA PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.     

<Superscript>68</Superscript>Ga-PSMA PET/CT Imaging Predicting Intraprostatic Tumor Extent,Extracapsular Extension and Seminal Vesicle Invasion Prior to Radical Prostatectomy in Patients with Prostate Cancer

Purpose

⁶⁸Ga-labeled prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) has shown promising results in patients with biochemical recurrence after primary therapy for prostate cancer. In this study, we evaluated the usefulness of PSMA I&T (imaging and therapy) PET/CT prior to radical prostatectomy.

Methods

The study population consisted of 21 patients with prostate cancer who underwent ⁶⁸Ga-PSMA I&T PET/CT before either open or laparoscopic radical prostatectomy. Intraprostatic tumor extent, extracapsular extension (ECE) and seminal vesicle invasion (SVI) were assessed on the PET/CT scans. Tracer uptake was quantified in terms of standardized uptake values (SUVs). Imaging findings were correlated with final whole-gland histopathology.

Results

Of the 21 patients, two had T stage 2b disease, nine stage 2c, six stage 3a and four stage 3b. The median Gleason score was 7. The SUV_mean of the primary tumors was 9.5?±?8.8. SUV_mean was higher in tumors with ECE than in organ-confined tumors (13.8?±?11.0 vs. 5.6?±?3.2, p?=?0.029). Peak tracer uptake was significantly positively correlated with Gleason score (r _s?=?0.49, p?=?0.025). Sensitivity, specificity, positive predictive value and negative predictive value were, respectively, 94.7%, 75.0%, 97.3% and 60.0% for tumor infiltration of an individual prostate lobe, 75.0%, 100.0%, 100.0% and 97.4% for SVI, and 90.0%, 90.9%, 90.0% and 90.9% for ECE, using an angulated contour of the prostate as the criterion. Tumor volume derived from ⁶⁸Ga-PSMA I&T PET/CT was significantly correlated with preoperative prostate-specific antigen value (r _p?=?0.75, p?<?0.001) and tumor volume on histopathology (r _p?=?0.45, p?=?0.039).

Conclusions

⁶⁸Ga-PSMA I&T PET/CT prior to radical prostatectomy can contribute to presurgical local staging of prostate cancer. In this pilot study, ⁶⁸Ga-PSMA I&T PET/CT showed promising results for prediction of lobe infiltration, ECE and SVI.

     

<Superscript>68</Superscript>Ga-PSMA PET-CT Imaging of Metastatic Adenoid Cystic Carcinoma

A patient with a history of adenoid cystic carcinoma of the nasal cavity presented himself with bone pain and an elevated PSA level. On suspicion of metastatic prostate cancer a ⁶⁸Ga-PSMA PET-CT was performed. The PET-CT showed numerous lung and non-sclerotic bone metastasis. Biopsy of a bone metastasis was performed and pathology showed adenoid cystic carcinoma instead of prostate cancer. Immunohistochemical PSMA staining of the primary tumour showed intense PSMA expression in adenoid cystic carcinoma tumour cells. Because of the high PSMA expression of adenoid cystic carcinoma, ⁶⁸Ga-PSMA PET-CT might be a promising imaging modality for this malignancy.     

The accuracy of <Superscript>68</Superscript>Ga-PSMA PET/CT in primary lymph node staging in high-risk prostate cancer

Purpose

To assess the diagnostic accuracy of ⁶⁸Ga-PSMA PET in predicting lymph node (LN) metastases in primary N staging in high-risk and very high-risk nonmetastatic prostate cancer in comparison with morphological imaging.

Methods

This was a multicentre trial of the Society of Urologic Oncology in Turkey in conjunction with the Nuclear Medicine Department of Cerrahpasa School of Medicine, Istanbul University. Patients were accrued from eight centres. Patients with high-risk and very high-risk disease scheduled to undergo surgical treatment with extended LN dissection between July 2014 and October 2015 were included. Either MRI or CT was used for morphological imaging. PSMA PET/CT was performed and evaluated at a single centre. Sensitivity, specificity and accuracy were calculated for the detection of lymphatic metastases by PSMA PET/CT and morphological imaging. Kappa values were calculated to evaluate the correlation between the numbers of LN metastases detected by PSMA PET/CT and by histopathology.

Results

Data on 51 eligible patients are presented. The sensitivity, specificity and accuracy of PSMA PET in detecting LN metastases in the primary setting were 53%, 86% and 76%, and increased to 67%, 88% and 81% in the subgroup with of patients with ≥15 LN removed. Kappa values for the correlation between imaging and pathology were 0.41 for PSMA PET and 0.18 for morphological imaging.

Conclusions

PSMA PET/CT is superior to morphological imaging for the detection of metastatic LNs in patients with primary prostate cancer. Surgical dissection remains the gold standard for precise lymphatic staging.

     

<Superscript>68</Superscript>Ga-PSMA PET/CT in the evaluation of bone metastases in prostate cancer

Purpose

The aims of this retrospective analysis were to compare ⁶⁸Ga-PSMA PET findings and low-dose CT findings (120 kV, 30 mA), and to obtain semiquantitative and quantitative ⁶⁸Ga-PSMA PET data in patients with prostate cancer (PC) bone metastases.

Methods

In total, 152 PET/CT scans from 140 patients were evaluated. Of these patients, 30 had previously untreated primary PC, and 110 had biochemical relapse after treatment of primary PC. All patients underwent dynamic PET/CT scanning of the pelvis and lower abdomen as well as whole-body PET/CT with ⁶⁸Ga-PSMA-11. The PET/CT scans were analysed qualitatively (visually), semiquantitatively (SUV), and quantitatively based on a two-tissue compartment model and a noncompartmental approach leading to the extraction of the fractal dimension. Differences were considered significant for p values <0.05.

Results

In total, 168 ⁶⁸Ga-PSMA-positive and 113 CT-positive skeletal lesions were detected in 37 patients (8 with primary PC, 29 with biochemical recurrence). Of these 168 lesions, 103 were both ⁶⁸Ga-PSMA PET-positive and CT-positive, 65 were only ⁶⁸Ga-PSMA-positive, and 10 were only CT-positive. The Yang test showed that there were significantly more ⁶⁸Ga-PSMA PET-positive lesions than CT-positive lesions. Association analysis showed that PSA plasma levels were significantly correlated with several ⁶⁸Ga-PSMA-11-associated parameters in bone metastases, including the degree of tracer uptake (SUV_average and SUV_max), its transport rate from plasma to the interstitial/intracellular compartment (K₁), its rate of binding to the PSMA receptor and its internalization (k₃), its influx rate (K_i), and its distribution heterogeneity.

Conclusion

⁶⁸Ga-PSMA PET/CT is a useful diagnostic tool in the detection of bone metastases in PC. ⁶⁸Ga-PSMA PET visualizes more bone metastases than low-dose CT. PSA plasma levels are significantly correlated with several ⁶⁸Ga-PSMA PET parameters.

     

Detection of recurrent prostate cancer lesions before salvage lymphadenectomy is more accurate with <Superscript>68</Superscript>Ga-PSMA-HBED-CC than with <Superscript>18</Superscript>F-Fluoroethylcholine PET/CT

Aim

[⁶⁸Ga]PSMA-HBED-CC (⁶⁸Ga-PSMA) is a novel and promising tracer for highly sensitive combined integrated positron emission tomography and X-ray computed tomography (PET/CT) diagnosis of recurrent prostate cancer (PCA). Our aim was to assess the sensitivity, specificity, positive and negative predictive value (PPV/NPV), and accuracy per lesion, as well as the positive predictive value per patient of ⁶⁸Ga-PSMA PET/CT using post-lymphadenectomy histology as a standard, and to compare these values to those obtained in a patient collective scanned using ¹⁸F-Fluoroethylcholine (¹⁸FEC) PET/CT.

Methods

Thirty eight patients had ¹⁸FEC and 28 patients had ⁶⁸Ga-PSMA. We performed a pelvic and/or retroperitoneal lymphadenectomy, if necessary supplemented by resection of locally recurrent lesions in accordance with imaging results.

Results

In 30/38 ¹⁸FEC and 23/28 ⁶⁸Ga-PSMA patients ≥1 focus of PCA was identified in postsurgical histology, leading to a per-patient PPV of 78.9 % for ¹⁸FEC and 82.1 % for ⁶⁸Ga-PSMA. In ¹⁸FEC and ⁶⁸Ga-PSMA patients, a total of 378 and 308 lymph nodes and local lesions were removed, respectively. For ¹⁸FEC and ⁶⁸for Ga-PSMA, the respective sensitivity (95 % confidence interval) was 71.2 % (64.5–79.6 %) and 86.9 % (75.8–94.2 %), specificity was 86.9 % (82.3–90.6 % ) and 93.1 % (89.2–95.9 %), PPV was 67.3 % (57.7–75.9 %) and 75.7 % (64.0–98.5 %), NPV was 88.8 % (84.4–92.3 %) and 96.6 % (93.5–98.5 %), and accuracy was 82.5 % (78.3–86.8 %) and 91.9 % (88.7 %–95.1 %).

Conclusion

In the present series Ga-PSMA PET/CT shows a better performance than FEC PET/CT with a significantly higher NPV and accuracy for the detection of locoregional recurrent and/or metastatic lesions prior to salvage lymphadenectomy.

     

Preliminary results on response assessment using <Superscript>68</Superscript>Ga-HBED-CC-PSMA PET/CT in patients with metastatic prostate cancer undergoing docetaxel chemotherapy

Purpose

To investigate the value of ⁶⁸Ga-HBED-CC PSMA (⁶⁸Ga-PSMA) PET/CT for response assessment in metastatic castration-sensitive and castration-resistant prostate cancer (mCSPC and mCRPC) during docetaxel chemotherapy.

Methods

⁶⁸Ga-PSMA PET/CT was performed in seven mCSPC patients before and after six cycles of upfront docetaxel chemotherapy and in 16 mCRPC patients before and after three cycles of palliative docetaxel chemotherapy. Radiographic treatment response was evaluated separately on the ⁶⁸Ga-PSMA PET and CT datasets. Changes in ⁶⁸Ga-PSMA uptake (SUVmean) were assessed on a per-patient and a per-lesion basis using the PERCIST scoring system with slight modification. Treatment response was defined as absence of any PSMA uptake in all target lesions on posttreatment PET (complete response, CR) or a decrease in summed SUVmean of ≥30% (partial response, PR). The appearance of a new PET-positive lesion or an increase in summed SUVmean of ≥30% (progressive disease, PD) indicated nonresponse. A moderate change in summed SUVmean (between ?30% and +30%) without a change in the number of target lesions was defined as stable disease (SD). For treatment response assessment on CT, RECIST1.1 criteria were used. Radiographic responses on ⁶⁸Ga-PSMA PET [RR(PET)] and on CT [RR(CT)] were compared and correlated with biochemical response (BR). A decrease in serum PSA level of ≥50% was defined as biochemical PR.

Results

Biochemical PR was found in six of seven patients with mCSPC (86%, 95% confidence interval 42% to 99.6%). The concordance rate was higher between BR and RR(PET) than between BR and RR(CT) (6/7 vs. 3/6 patients. ⁶⁸Ga-PSMA PET and CT were concordant in only three patients (50%, 12% to 88%). In mCRPC patients, biochemical PR was found in six of 16 patients (38%, 15% to 65%). Outcome prediction was concordant between BR and RR(PET) in nine of 16 patients (56%), and between BR and RR(CT) in only four of 12 patients (33%) with target lesions on CT. ⁶⁸Ga-PSMA PET and CT results corresponded in seven of 12 patients (58%, 28% to 85%).

Conclusion

Our preliminary results suggest that ⁶⁸Ga-PSMA PET might be a promising method for treatment response assessment in mCSPC and mCRPC. The data indicate that for different metastatic sites, the performance of ⁶⁸Ga-PSMA PET in response assessment might be superior to that of the conventional CT approach and could help differentiate between progressive disease and treatment response. Because of the limited number of patients, the differences revealed in our study were not statistically significant. Thus larger and prospective studies are clearly needed and warranted to confirm the value of ⁶⁸Ga-PSMA PET as an imaging biomarker for response assessment.

     

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

⁶⁸Ga-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 ⁶⁸Ga-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. SUV_mean 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 ⁶⁸Ga-PSMA ligand was used. Moreover, direct comparison of SUVs from PET/CT and PET/MR needs to be conducted carefully.     

Reduction of <Superscript>68</Superscript>Ga-PSMA renal uptake with mannitol infusion: preliminary results

Purpose

Urea-based prostate-specific membrane antigen (PSMA) ligands labelled with ⁶⁸Ga or ¹⁷⁷Lu are new tracers with great potential for theranostic approaches in prostate cancer. However, clinical studies have shown that the kidneys are one of the off-target organs along with the salivary and lacrimal glands. In the kidneys, PSMA is physiologically expressed in the apical epithelium of the proximal tubules, and mannitol acts as an osmotic diuretic in these tubules. We investigated the potential of mannitol to reduce renal uptake of ⁶⁸Ga-PSMA.

Methods

Kidney uptake (SUVmax) was calculated in nine patients undergoing ⁶⁸Ga-PSMA PET/CT at baseline (b-PET/CT) and after intravenous infusion of 500 ml of 10% mannitol (m-PET/CT). Two different infusion schemes for mannitol were used: (1) 500 ml mannitol was infused over 40 min after ⁶⁸Ga-PSMA administration (A-infusion) and (2) 250 ml mannitol was infused over 15 min before and again after ⁶⁸Ga-PSMA administration (B-infusion).

Results

In patients receiving the A-infusion, mean SUV_max increased by 11.9% and 7.4% in the right and left kidney, respectively. In patients receiving the B-infusion, mean SUV_max decreased by 24.3% and 22.4% in the right and left kidney, respectively.

Conclusion

Our preliminary findings indicate that mannitol may play a role in reducing off-target ⁶⁸Ga-PSMA renal uptake. Administration of the osmotic diuretic should be rapid and start before ⁶⁸Ga-PSMA injection. These results warrant dosimetric studies in patients treated with ¹⁷⁷Lu-PSMA to find the best scheme for mannitol administration.

     

Comparison of PET imaging with a 68Ga-labelled PSMA ligand and 18F-choline-based PET/CT for the diagnosis of recurrent prostate cancer

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 (SUV_max) 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 SUV_max 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.     

Comparison of bone scintigraphy and <Superscript>68</Superscript>Ga-PSMA PET for skeletal staging in prostate cancer

Purpose

The aim of our study was to compare the diagnostic performance of ⁶⁸Ga-PSMA PET and ^99mTc bone scintigraphy (BS) for the detection of bone metastases in prostate cancer (PC) patients.

Methods

One hundred twenty-six patients who received planar BS and PSMA PET within three months and without change of therapy were extracted from our database. Bone lesions were categorized into benign, metastatic, or equivocal by two experienced observers. A best valuable comparator (BVC) was defined based on BS, PET, additional imaging, and follow-up data. The cohort was further divided into clinical subgroups (primary staging, biochemical recurrence, and metastatic castration-resistant prostate cancer [mCRPC]). Additionally, subgroups of patients with less than 30 days delay between the two imaging procedures and with additional single-photon emission computed tomography (SPECT) were analyzed.

Results

A total of 75 of 126 patients were diagnosed with bone metastases. Sensitivities and specificities regarding overall bone involvement were 98.7–100 % and 88.2–100 % for PET, and 86.7–89.3 % and 60.8–96.1 % (p?<?0.001) for BS, with ranges representing results for ‘optimistic’ or ‘pessimistic’ classification of equivocal lesions. Out of 1115 examined bone regions, 410 showed metastases. Region-based analysis revealed a sensitivity and specificity of 98.8–99.0 % and 98.9–100 % for PET, and 82.4–86.6 % and 91.6–97.9 % (p?<?0.001) for BS, respectively. PSMA PET also performed better in all subgroups, except patient-based analysis in mCRPC.

Conclusion

Ga-PSMA PET outperforms planar BS for the detection of affected bone regions as well as determination of overall bone involvement in PC patients. Our results indicate that BS in patients who have received PSMA PET for staging only rarely offers additional information; however, prospective studies, including a standardized integrated x-ray computed tomography (SPECT/CT) protocol, should be performed in order to confirm the presented results.

     

Patterns of relapse as determined by <Superscript>68</Superscript>Ga-PSMA ligand PET/CT after radical prostatectomy

Purpose

To evaluate the patterns of relapse and impact on the intended treatment when using ⁶⁸Ga-prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) imaging for restaging of disease in patients with biochemical relapse after radical prostatectomy (RP) before salvage radiotherapy (sRT).

Methods

In all, 39 patients with biochemical recurrence after RP who had no primary indication for adjuvant RT due to the absence of biologically unfavorable disease (e.g., extracapsular extension, seminal vesicle invasion, positive margins, or lymph node involvement) underwent a ⁶⁸Ga-PSMA ligand PET/CT for planning of sRT.

Results

PET/CT was positive in 84.6% (33/39) of patients. A total of 61 lesions were observed in these patients (on average 1.8 lesions per patient); 30.3% (10/33) of patients had locally recurrent disease in the prostatic bed. The clinical TNM stage (TNM: tumour-lymph nodes-metastasis-classification) was altered in 69.7% (23/33) of patients following PET, resulting in individualized treatment concepts. A prostate-specific antigen (PSA) >1.0?ng/mL was significantly associated with an increased risk of extrapelvic metastatic disease (p = 0.048). The PSA level at the time of PSMA ligand PET/CT correlated with the peak standardized uptake value (SUV_peak; p = 0.002). According to current clinical guidelines, the remaining 15.4% (6/39) of patients without evidence of disease on PET received sRT with a dose of 66.0?Gy.

Conclusion

Our results suggest that in patients with biochemical recurrence who did not receive early sRT, a ⁶⁸Ga-PSMA ligand PET/CT for restaging of disease allows for tailoring and individualizing treatment. Particularly in patients with PSA levels above 1.0?ng/mL, a ⁶⁸Ga-PSMA ligand PET/CT should be performed for therapy planning, since patients often have metastases not confined to the pelvis.

     

The impact of [<Superscript>68</Superscript>Ga]PSMA I&amp;T PET/CT on radiotherapy planning in patients with prostate cancer

Purpose

To determine the impact of Gallium-68-labled prostate-specific membrane antigen positron-emission tomography/computed tomography ([⁶⁸Ga]PSMA PET/CT) on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer.

Methods

A total of 106 patients with prostate cancer scheduled for radiation therapy underwent 120 [⁶⁸Ga]PSMA PET/CT scans prior to radiotherapy treatment. In 20 cases, patients underwent [⁶⁸Ga]PSMA PET/CT for primary therapy (PT), 75 cases were referred for biochemical relapse after surgery (RL), and 25 cases were intended for palliative treatment of localized metastases (MD). We retrospectively compared the impact of [⁶⁸Ga]PSMA PET/CT on lesion detection and treatment decision to CT alone.

Results

[⁶⁸Ga]PSMA PET/CT revealed a total of 271 positive lesions, whereas CT detected 86 lesions (32%). Overall, the radiotherapy regime was changed in 55 of 120 cases (46%) based on the higher detection rate of [⁶⁸Ga]PSMA PET/CT: in 15% of cases with PT, in 43% of cases with RL, and in 44% of cases with MD.

Conclusion

[⁶⁸Ga]PSMA PET/CT is superior to CT alone for lesion detection in prostate cancer, thereby significantly impacting on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer.

     

<Superscript>68</Superscript>Ga-PSMA I&amp;T PET/CT for assessment of prostate cancer: evaluation of image quality after forced diuresis and delayed imaging

Objective

Urinary radiotracer excretion of ⁶⁸Ga-Labelled prostate-specific membrane antigen (PSMA) ligands may complicate the assessment of the prostate region and differentiation of lymph nodes from ureteral activity. The aim of this study was to assess the value of delayed imaging after forced diuresis.

Materials and methods

Sixty-six patients underwent ⁶⁸Ga-PSMA I&T PET/CT for evaluation of prostate cancer at 60 min post-injection. In subgroups of patients, this was amended by delayed imaging after 180 min post-injection, preceded by furosemide and oral hydration early, at the time of tracer injection, or delayed, at 100 min post-injection. Urinary tracer activity within the bladder and focal ureteral activity was analyzed.

Results

After forced diuresis, linear and focal visualization of ureters was significantly reduced. After delayed furosemide, mean and peak bladder activity decreased (p?<?0.001), and image quality of the prostate region improved on delayed images (p?<?0.001). Early furosemide co-injection with tracer resulted in increased mean and peak bladder activity (p?<?0.001) and in deteriorated image quality of the prostate region on delayed images (p?=?0.008).

Conclusion

Ga-PSMA I&T PET/CT delayed imaging after forced diuresis can improve the assessment of prostate region and pelvic lymph nodes by removing excreted tracer from the lower urinary tract.

Key points

? Forced diuresis can improve image quality in ⁶⁸ Ga-PSMA I&T.? After forced diuresis, linear and focal visualization of ureters was reduced.? Timing of diuresis relative to ⁶⁸ Ga-PSMA I&T injection is important.? Early furosemide co-injection with tracer resulted in deteriorated image quality on delayed images.? After delayed furosemide, image quality improved on delayed images.

     

Intra-individual comparison of <Superscript>68</Superscript>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 ⁶⁸Ga-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.

     

Comparison of standard and delayed imaging to improve the detection rate of [<Superscript>68</Superscript>Ga]PSMA I&amp;T PET/CT in patients with biochemical recurrence or prostate-specific antigen persistence after primary therapy for prostate cancer

Purpose

The aim of this study was to assess the value of dual-time point imaging in PET/CT for detection of biochemically recurrent or persistent prostate cancer, using the prostate-specific membrane antigen (PSMA) ligand [⁶⁸Ga]PSMA I&T.

Methods

240 patients who underwent a [⁶⁸Ga]PSMA I&T PET/CT in the context of biochemical relapse of prostate cancer were included in this retrospective analysis. Imaging consisted of a standard whole-body PET/CT (1 h p.i.), followed by delayed (3 h p.i.) imaging of the abdomen. PSA-stratified proportions of positive PET/CT results, standardized uptake values and target-to-background ratios were analyzed, and compared between standard and delayed imaging.

Results

The overall detection rates of [⁶⁸Ga]PSMA I&T PET/CT were 94.2, 71.8, 58.6, 55.9 and 38.9% for PSA levels of ≥2, 1 to <2, 0.5 to <1, >0.2 to <0.5, and 0.01 to 0.2 ng/mL, respectively. Although the target-to-background ratio improved significantly over time (P?<?0.0001), the majority (96.6%) of all lesions suggestive of recurrent disease could already be detected in standard imaging. Delayed imaging at 3 h p.i. exclusively identified pathologic findings in 5.4% (10/184) of abnormal [⁶⁸Ga]PSMA I&T PET/CT scans, and exclusively detected 3.4% (38/1134) of all lesions suggestive of recurrent disease.

Conclusions

[⁶⁸Ga]PSMA I&T PET/CT shows high detection rates in patients with prostate-specific antigen persistence or biochemical recurrence of prostate cancer. Delayed imaging can detect lesions with improved contrast compared to standard imaging. However, the impact on detection rates was limited in this study.