Material and Method: A total of 234 consecutive patients with advanced prostate cancer who underwent ⁶⁸Ga-PSMA PET/CT were included in this retrospective study. Data on previous treatments, Gleason score, serum Prostate Specific Antigen (PSA) levels (ng/mL) and ⁶⁸Ga-PSMA PET/CT findings were recorded.

Results: The mean age of the patients was 67.6 ± 8.5 years. Median PSA level was 21.7 (0.2-880) ng/ml. Pelvic (41%) and abdominal (30.3%) lymph nodes were the most commonly involved lymph nodes, while bone metastases were multimetastatic and bone carcinomatosis in 22.2% and 30.6% of patients, respectively. Other common distant organ metastases were lung (7.6%) and liver (7.2%) metastases. Level 1-4 lymph node positivity was noted in 29.4%, 33.3% and 6.8% of patients with liver metastasis, lung metastasis and seminal vesicle invasion, respectively. Concomitant lung metastasis was evident in 41.1% of patients with liver metastasis, while lung or liver metastasis was evident in 13.6% of patients with seminal vesicle invasion. Bone metastasis was evident in all patients with liver and lung metastasis, and in 65.9% of patients with seminal vesicle invasion.

Conclusion:The findings of this study showed the value of ⁶⁸Ga-PSMA PET/CT in detecting coexistence rate of metastases in advanced prostate cancer.

Recurrent PCa is defined as an increase in two consecutive measurements of Prostate Specific Antigen (PSA) > 0.2 ng / ml ². Because it changes the approach of local or systemic treatment, early detection of metastatic spread and biochemical recurrence in prostate cancer is important ^3,4. The main approaches to the progression of advanced prostate cancer, such as prostatespecific antigen (PSA), computed tomography (CT) and bone scan, have some diagnostic limitations ^5-7.

The sensitivity of ¹¹C or ¹⁸F Cholinelabeled PET/CT tracers in patients with a PSA level of <1ng/mL has been reported as low as 19-36% ^8-10. Therefore, an imaging method with higher sensitivity and specificity is required.

Prostate specific membrane antigen (PSMA) is a type II membrane protein consisting of 750 amino acids. PSMA is expressed in the normal prostate tissue and is highly expressed in the primary and metastatic prostate cancer ¹¹.

The use of radiolabeled tracers acting as PSMA ligands for PET/CT is a novel diagnostic option in this context and gallium 68 (⁶⁸Ga) has emerged as a PSMA ligand and a promising new PET tracer in the diagnostic work-up of prostate cancer patients over the past few years ^12-15.

The ⁶⁸Ga-PSMA ligand for imaging and therapy (I&T) PET/CT (⁶⁸Ga-PSMA-I&T PET/CT) has been associated with promising results including a substantially higher diagnostic accuracy for the detection of prostate cancer metastases compared to choline-based PET/CT, particularly in the case of lymph node metastases and at low PSA levels ^12,16-18).

This study was therefore designed to evaluate the con-comitant metastases rate of advanced prostate cancer patients by means of 68Ga-PSMA-I&T PET/CT in a retrospective cohort.

The study was conducted in full accordance with local Good Clinical Practice guidelines and current legislation, and permission was obtained from the Institutional Ethics Committee for the use of patient data for publication purposes (permit no: 057/2018).

Study Parameters
Data on previous treatments (radical prostatectomy, radiotherapy, androgen-deprivation therapy), Gleason score, serum PSA levels (ng/mL), ⁶⁸Ga-PSMA-I&T PET/CT findings on lymph node and distant organ metastases were recorded for each patient. Concomitant metastasis and level of lymph node positivity with respect to distant organ metastasis were also evaluated.

PSMA-PET/CT
The ⁶⁸Ga PSMA I&T was synthesized using the ⁶⁸Ge/⁶⁸Ga generator (iThemba. Labs, S.A) linked radiopharmacy application module (SCINTOMICS GmbH, Fürstenfeldbruck, Germany), disposable cassette kit (ABX, Radeberg, Germany), 22.5 μg (15 nmol), and unbound PSMA I&T peptide (SCINTOMICS GmbH, Fürstenfeldbruck, Germany) entirely automatically, following the Good Manufacturing Practice (GMP) procedures. Following high performance liquid chromatography-based quality control, 2 MBq/kg of ⁶⁸Ga-PSMA was injected. This was followed 60 minutes later by acquisition of contrast-CT (120 kV, 110 mA, 600 mm transaxial FOV, no gap, 10Å~1.5 mm collimation, pitch 1.1, 0.5 s rotation time, 5 mm slice thick-ness, 512Å~512 matrix) and then PET emission data (3D FOV 15,5 cm, OSEM 2 iterations/8 subset, FWHM 5mm) for 3 minutes per supine position craniocaudally to the level of lower limbs via a dedicated PET/CT system (Siemens Biograph 6; Siemens, Knoxville, TX, USA).

Image Analysis
PET/CT images were visually analyzed for the presence and localization of suspicious lesions and interpreted by nuclear medicine physicians with 10 years of experience. The uptake characteristics in metastases were quantified using maximum standardized uptake values (SUVmax) of tumor lesions, which was calculated for lesions judged positive via volumes of interest (VOIs) drawn automatically. Local recurrences, lymph node metastasis (Level 1: pelvic, Level 2: abdominal, Level 3: mediastinal and Level 4: supraclavicular and/or neck), bone metastases (1 metastatic site: oligometastatic, 2-20 metastatic sites: multimetastatic and >20 metastatic sites: bone carcinomatosis) and other metastatic sites (lung, liver, adrenal gland, pleural/peritoneal metastases) were documented. Examples of patients undergoing ⁶⁸Ga-PSMA ligand PET/CT examination for metastases were presented in Figure 1A and Figure 1B.

Click Here to Zoom

Figure 1A: 68Ga-PSMA PET-CT findings related to 68Ga-PSMA ligand uptake showing: malignant lesion in the prostate gland, seminal vesicle involvement, lymph node invasion and bone metastases in an 82-year old prostate cancer patient with prostate SUV max of 21.7, Gleason score of 9 and PSA level of 108 ng/ml.

Click Here to Zoom

Figure 1B: 68Ga-PSMA PET-CT findings related to 68Ga-PSMA ligand uptake showing: mediastinal lymph node invasion, bone and liver metastases in a 62-year old prostate cancer patient with liver SUV max of 18.3, Gleason score of 10 and PSA level of 880 ng/ml.

Statistical Analysis
Statistical analysis was made using IBM SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY). Descriptive statistics were reported and data were expressed as “mean ± (standard deviation; SD)”, median (minimum-maximum) and percentage (%) where appropriate.

Click Here to Zoom

Table 1: The clinical characteristics of patients with advanced prostate carcinoma (n =234).

Tumor-Metastasis Characteristics
Mean (SD) Gleason score was 8.1 ± 1.0 and median PSA level was 21.7 (0.2-880) ng/ml. The median SUVmax of pelvic lymph node was 10.5, compared to a median SUVmax of 11.9, 10.8 and 8.7 in abdominal, mediastinal and supraclavicular and/or neck lymph node tissue, respectively. Median SUVmax of 10.1, 4.3 and 11.9 was noted in liver, lung and bone tissue, respectively (Table 1).

The size of positive lymph nodes ranged from 13.9 ± 6.8 (5-29) mm for supraclavicular and/or neck lymph nodes to 19.3 ± 10.8 (6-54) mm for abdominal lymph nodes. The most commonly involved lymph nodes were pelvic (41%), abdominal (30.3%), mediastinal (11.1%) and supraclavicular and/or neck (9.8%) lymph nodes. Bone metastases were oligometastatic, multi-metastatic and in 8.9% and 22.2% of patients, respectively, while bone carcinomatosis was noted in 30.6% of patients. Other common distant organ metastases were lung (7.6%) and liver (7.2%) metastases (Table 1

Lymph Node Positivity in Patients with Respect to the Type of Metastasis
Level 1-4 lymph node positivity was noted in 29.4%, 33.3% and 6.8% of patients with liver metastasis, lung metastasis and seminal vesicle invasion, respectively. Level 1-2 lymph node positivity was more common for bone metastasis, comprising all lymph node metastasis for the oligometastatic stage (19% for each) with high rates in multimetastatic (21% and 15.3%, respectively) bone lesions or bone carcinomatosis (10.9% and 15%, respectively) (Table 2).

Click Here to Zoom

Table 2: Lymph node positivity in patients with respect to type of metastasis.

Concomitant lung metastasis was evident in 41.1% of patients with liver metastasis, while lung or liver metastasis was evident in 3.6% of patients with seminal vesicle invasion (Table 2).

Bone metastasis was evident in all patients with liver (multimetastatic in 41.1%, bone carcinomatosis in 52.9%) and lung (multimetastatic in 27.7%, bone carcinomatosis in 61.1%) metastases, and in 65.9% of patients with seminal vesicle invasion (oligometastatic in 9.0%, multimetastatic in 15.9%, bone carcinomatosis in 40.9%) (Table 2). In patients with oligometastatic stage bone metastasis, no concomitant lung or liver metastases or level 3-4 lymph node metastases were determined whereas there was positivity of seminal vesicle invasion.

In the current cohort: lymph node metastases in 46.1% of patients and bone metastases in 61.9%, as well as pulmonary (7.6%), hepatic (7.2%), adrenal (2.5%), peritoneal and (0.8%), pleural (2.9%) metastases in a previous retrospective analysis of 240 patients with prostate cancer, ⁶⁸Ga PSMA I&T PET/CT revealed lymph node metastases in 62.5% of patients and bone metastases in 33.7%, together with local recurrences (26.6%) as well as pulmonary (4%), hepatic (2%), adrenal (1%), peritoneal (0.5%), muscular (0.5%) and testicular (0.5%) metastases ¹⁹. In another retrospective analysis of 101 patients with increased PSA levels after radical prostatectomy, the ⁶⁸Ga-PSMA-I&T PET/CT revealed lymph node metastases in 73.3% of patients and bone metastases in 30.7%, together with local recurrences (16.8%) and other metastases (5.9%) ²⁰. In a retrospective analysis of 83 consecutive patients (PSA: 0.81, range: 0.01 - 128 ng/mL) with biochemical relapse after prostatectomy, the ⁶⁸Ga PSMA I&T PET/CT revealed local recurrent cancer in 22% of the patients, lymph node metastases in 35% and distant metastases in 18% ¹⁷.

In a retrospective analysis of the diagnostic value of ⁶⁸Ga-PSMA PET/CT in 901 representative tumor lesions of 319 patients, 13 lesions were defined as local relapses after prostatectomy, while 328 were reported as lymph node metastases, 359 as bone metastases, 129 as soft tissue metastases and 72 as vital tumor lesions within the prostate gland ²¹.

In our patient group, median SUVmax in lymph nodes ranged from 8.7 in supraclavicular and/or neck lymph nodes to 11.9 in abdominal lymph nodes, while the size of lymph nodes detected via ⁶⁸Ga-PSMA PET/CT ranged from 13.9 (range: 5-29) mm (neck lymph nodes) to 19.3 (range: 6-29) mm (abdominal lymph nodes). Similarly, in a retrospective analysis of 90 patients with prostate cancer referred for ⁶⁸Ga-PSMA PET/CT, lymph node metastasis was reported in 26.7% of patients together with median nodal diameter of 10.9 mm (range: 3.9–32.9) and SUVmax of 10.6 ¹².

In a previous study of 25 patients with biochemical recurrence after radical prostatectomy, ⁶⁸Ga-PSMA-I&T PET/CT revealed presence of lymph node metas-tases in 60.5% of patients and with SUVmax of 21.9 (ranged 4.2–89.0) ²².

The range (5-54 mm) for the size of lymph nodes de-tectable via ⁶⁸Ga-PSMA-I&T PET/CT in the current study seems notable given the significant difference reported in median size of lymph node metastases detected vs. undetected (13.6 versus 4.3 mm) via ⁶⁸Ga-PSMA PET/CT and the potential influence of lymph node metastasis size on the diagnostic accuracy of ⁶⁸Ga-PSMA PET/CT ²³.

The sensitivity and specificity of ⁶⁸Ga-PSMA PET/CT in the detection of lymph node metastasis has been reported to range from 61.1-80.0% and 90.0-100.0%, respectively in past studies ^6,12,21.

In accordance with consideration of bone as the most frequent site of metastatic spread in prostate cancer ²⁴ bone metastases were detected in 61.9 % of patients and with median SUVmax of 11.9 in our cohort. Compared to the current study findings of the diagnostic accuracy of ⁶⁸Ga-PSMA PET/CT in detecting bone metastasis, lower detection rates (12.2%) with similar SUV (SUVmax: 11.6) ¹² as well as lower detection rates (34.2-36%) ^22,25 with higher SUV (SUVmax: 27.1) ²² or lower PSA levels (median 1.99 ng/ml, ranged 0.2-59.4) ²⁵ have been reported among recurrent prostate cancer patients in past studies.

In a retrospective study of 155 consecutive patients with recurrent disease, the overall rate of bone metastases was reported as 32%, which ranged from 15% in patients with PSA <1 ng/ml to 39% in those with PSA ≥2 ng/ml ²⁶.

Accordingly, in a systematic review of 37 studies on the utility of ⁶⁸Ga-PSMA PET/CT for the detection of bone metastases, the prevalence of pathological bone lesions was reported ranging from 5% to 60% ²⁴. The authors concluded that the diagnostic performance of ⁶⁸Ga-PSMA PET/CT was higher with increased PSA levels and it was superior to bone scintigraphy in the detection of bone lesions in terms of sensitivity (99% vs 73%) and specificity (100% vs. 98%), whereas its diagnostic performance in progressive metastatic disease was considered as questionable ²⁴.

The lung was the second most common distant organ metastasis (7.6%) in our study and lung metastasis was associated with the lowest SUVmax scores (median 4.3) amongst other metastases. The lung has been considered as the second organ involved after bone in patients with prostate cancer, while the lack of any significant difference in SUVmax values between lung cancer and histologically proven prostate cancer has also been emphasized due to PSMA expression in tumor associated neovasculature in patients with primary lung cancer ^27,28. In fact, ⁶⁸Ga-PSMA PET/CT is considered less valuable in the lungs, since it fails to discriminate reliably between pulmonary metastases and primary lung cancer in prostate cancer patients ^7,28.

Gleason scores of > 7 or PSA levels ≥ 10 ng/ml have been associated with significantly higher uptake of ^{68Ga-PSMA in patients with prostate cancers 29, while the increasing rate of bone metastases has been reported with higher PSA levels or the PSA doubling time 24,26. This seems notable given the median Gleason score of 8 6-10 and median PSA level of 21.7 ng/mL (0.2-880) in the current study. Nonetheless, it has been emphasized that a continuous increase in PSA level does not automatically correlate with an increase in tumor detection 21 and a high PSA-value may also predict lower diagnostic performance of 68Ga-PSMA PET/CT for detection of affected regions due to a higher likelihood of microscopic spread 30.}

Given the earlier occurrence of increased PSMA ex-pression than the expected morphological alterations in bone metastases ³¹ and the superiority of 68Ga-PSMA-ligand imaging to morphological imaging in the detection of lymph node metastases ^7,32 the current study findings emphasize the role of ⁶⁸Ga-PSMA PET/CT in timely and accurate diagnosis of lymph node and bone involvement in patients with PSA persistence or progressive metastatic disease ^19,24. This seems critical in the management of prostate cancer in terms of potential for allowing planning of a more tailored therapeutic strategy and use of salvage procedures (e.g. secondary lymphadenectomy, targeted radiation therapy) with a potentially curative intent ^7,31,33,34. However, in unclear ⁶⁸Ga-PSMA PET positive lesions, further diagnostic work-up with morphological correlation and confirmation via other imaging techniques such as MRI, ultrasound or biopsy are considered necessary ⁷.

The current study findings also revealed data on the concomitant presence of lymph node and distant organ metastases. Level 1-4 lymph node positivity was evident in the presence of lung and liver metastasis or seminal vesicle invasion, whereas the presence of bone metastasis was associated with level 1-2 lymph node positivity. Although only 8.9% of bone metastases were at the oligometastatic stage compared with the detection of multi-metastatic bone metastases in 22.2% of patients in this cohort, it should be noted that bone metastasis was evident in all patients with liver and lung metastasis, while it was at the oligometastatic stage only in patients with seminal vesicle invasion.

This finding revealed an absence of concomitant lung or liver metastases and level 3-4 lymph node metastases, but positivity of seminal vesicle invasion in patients with oligometastatic stage bone metastasis. This seems notable given that prompt detection of prostate cancer recurrence is considered of critical importance since metastases are more likely to be locally confined or oligometastatic at this point enabling the use of metastasis-directed therapies, both lymphadenectomy and radiotherapy ⁶.

This study has some limitations: The first is retrospec-tive, single centered, study in a certain date range. A second limitation is the lack of histological validation for positive findings on ⁶⁸Ga-PSMA PET/CT. Despite these limitations, this study will provide valuable literary contributions to metastases in prostate cancer patients.

In conclusion, the findings of this retrospective cohort of patients with advanced prostate cancer showed the value of ⁶⁸Ga-PSMA PET/CT in detecting coexistence rates of metastases in advanced prostate cancer.

Acknowledgements
The research was not financially supported by grants or any other kind of funding from any pharmaceutical company or other possible sources. All the authors had an active involvement in data collection and analysis, as well as writing, preparing and reviewing the manuscript.

Author contributions: All authors designed the study, analyzed the data and contributed to the writing of the paper. All authors statistically analyzed the data. All authors contributed to the writing of the paper. All the authors accept responsibility for the data and the accuracy of the data analysis.

Source of founding:
Conflicts of interest: The authors have no conflict of interests to declare.

Financial Disclosure: The authors declared that this study has received no financial support.

1) Arnold M, Karim-Kos HE, Coebergh JW, et al. Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European Cancer Observatory. Eur J Cancer 2015; 51: 1164-87.

2) Stephenson AJ, Kattan MW, Eastha m JA, et al. Defining biochemical recurrence of prostate cancer after radical prostatectomy: a proposal for a stand-ardized definition. J Clin Oncol 2006; 24: 3973-8.

3) Ost P, Decaestecker K, Lambert B, et al. Prognostic factors influencing prostate cancer-specific survival in non-castrate patients with metastatic prostate cancer. Prostate 2013; 74: 297-305.

4) Mottet N, Bellmunt J, Bolla M, et al. EAU guide-lines on prostate cancer part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 2011; 59: 572-883.

5) Henkenberens C, VON Klot CA, Ross TL, et al. ⁶⁸Ga-PSMA Ligand PET/CT-based radiotherapy for lymph node relapse of prostate cancer after primary therapy delays initiation of systemic therapy. Anticancer Res 2017; 37: 1273-9.

6) Udovicich C, Perera M, Hofman MS, et al. ⁶⁸Gaprostate-specific membrane antigen-positron emis-sion tomography/computed tomography in advanced prostate cancer: Current state and future trends. Prostate Int 2017; 5: 125-9.

7) Rauscher I, Maurer T, Fendler WP, Sommer WH, Schwaiger M, Eiber M. (68)Ga-PSMA ligand PET/CT in patients with prostate cancer: How we review and report? Cancer Imaging 2016; 16: 14.

8) Mottet N, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol 2017; 71: 618-29.

9) McGrath S, Christidis D, Perera M, et al. Prostate cancer biomarkers: Are we hitting the mark? Prostate Int 2016; 4: 130-5.

10) Graziani T, Ceci F, Castellucci P, et al. (11)C-choline PET/CT for restaging prostate cancer. Results from 4,426 scans in a single-centre patient se-ries. Eur J Nuc Med Mol Imaging 2016; 43: 1971-9.

11) Evangelista L, Briganti A, Fanti S, et al. New clinical indications for ¹⁸F/¹¹C-choline, new tracers for positron emission tomography and a promising hybrid device for prostate cancer staging: a sys-tematic review of the literature. Eur Urol 2016; 70: 161-75.

12) Uprimny C, Kroiss AS, Decristoforo C, et al. ⁶⁸Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour. Eur J Nucl Med Mol Imaging 2017; 44: 941-9.

13) Kitajima K, Murphy RC, Nathan MA, Sugimura K. Update on positron emission tomography for imaging of prostate cancer. Int J Urol 2014; 21: 12-23.

14) Afshar-Oromieh A, Malcher A, Eder M, et al. PET imaging with a [⁶⁸Ga]gallium-labelled PSMA lig-and for the diagnosis of prostate cancer: biodistri-bution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging 2013; 40: 486-95.

15) Ceci F, Uprimny C, Nilica B, et al. (68)Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate? Eur J Nucl Med Mol Imaging 2015; 42: 1284-94.

16) McCarthy M, Langton T, Kumar D, Campbell A . Comparison of PSMA-HBED and PSMA-I&T as diagnostic agents in prostate carcinoma. Eur J Nuc Med Mol Imaging 2017; 44: 1455-62.

17) Berliner C, Tienken M, Frenzel T, et al . Detection rate of PET/CT in patients with biochemical relapse of prostate cancer using [(68)Ga]PSMA I&T and comparison with published data of [(68)Ga]PSMA HBED-CC. Eur J Nuc Med Mol Imaging 2017; 44: 670-7.

18) Bluemel C, Krebs M, Polat B, et al. ⁶⁸Ga-PSMA-PET/CT in patients with biochemical prostate cancer recurrence and negative ¹⁸F-Choline-PET/CT. Clin Nuc Med 2016; 41: 515-21.

19) Schmuck S, Nordlohne S, von Klot CA, et al. Comparison of standard and delayed imaging to improve the detection rate of [⁶⁸Ga]PSMA I&T PET/CT in patients with biochemical recurrence or prostate-specific antigen persistence after primary therapy for prostate cancer. Eur J Nucl Med Mol Imaging 2017; 44: 960-8.

20) Schmuck S, von Klot CA, Henkenberens C, et al. Initial experience with volumetric 68Ga-PSMA I&T PET/CT for assessment of whole-body tumor burden as a quantitative imaging biomarker in patients with prostate cancer. J Nucl Med 2017; 58:1962-8.

21) Afshar-Oromieh, Avtzi E, Giesel FL, et al. The diagnostic value of PET/CT imaging with the (68)Galabelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2015; 42: 197-209.

22) Derlin T, Schmuck S, Juhl C, et al. Imaging characteristics and first experience of [⁶⁸Ga]THP-PSMA, a novel probe for rapid kit-based Ga-68 labeling and PET imaging: comparative analysis with [68Ga]PSMA I&T. Mol Imaging Biol 2018 Jan 17. doi: 10.1007/s11307-018-1160-8.

23) Budäus L, Leyh-Bannurah SR, Salomon G, et al. Initial experience of (68)Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur Urol 2016; 69: 393-6.

24) Zacho HD, Nielsen JB, Haberkorn U, Stenholt L, Petersen LJ. ⁶⁸Ga-PSMA PET/CT for the detection of bone metastases in prostate cancer: a systematic review of the published literature. Clin Physiol Funct Imaging 2017 Oct 29. doi: 10.1111/cpf.12480.

25) Eiber M, Maurer T, Souvatzoglou M, et al. Evaluation of hybrid ⁶⁸Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med 2015; 56: 668-74.

26) Verburg FA, Pfister D, Heidenreich A, et al. Ex-tent of disease in recurrent prostate cancer determined by [(68)Ga]PSMA-HBED-CC PET/CT in relation to PSA levels, PSA doubling time and Gleason score. Eur J Nucl Med Mol Imaging 2016; 43: 397-403.

27) Bubendorf L, Schopher A, Wagner U, et al. Metastatic patterns of prostate cancer: an autopsy study of 1.589 patients. Hum Pathol 2000; 31: 578-83.

28) Pyka T, Weirich G, Einspieler I, et al. ⁶⁸Ga-PSMA-HBED-CC PET for differential diagnosis of suggestive of lung lesions in patients with pros-tate cancer. J Nucl Med 2016; 57: 367-71.

29) Corfield J, Perera M, Bolton D, Lawrentschuk N. ⁶⁸Gaprostate specific membrane antigen (PSMA) positron emission tomography (PET) for primary staging of high-risk prostate cancer: a systematic review. World J Urol 2018 Jan 17. doi: 10.1007/s00345-018-2182-1.

30) Jilg CA, Drendel V, Rischke HC, et al. Diagnostic Accuracy of Ga-68-HBED-CC-PSMA-Ligand-PET/CT before salvage lymph node dissection for recurrent prostate cancer. Theranostics 2017; 7: 1770-80.

31) Sachpekidis C, Bäumer P, Kopka K, et al. ⁶⁸Ga-PSMA PET/CT in the evaluation of bone metastases in prostate cancer. Eur J Nucl Med Mol Imag-ing 2018 Jan 23. doi: 10.1007/s00259-018-3936-0.

32) Maurer T, Gschwend JE, Rauscher I, et al. Diagnostic efficacy of Gallium-PSMA positron emission tomography compared to conventional imag-ing in lymph node staging of 130 consecutive patients with intermediate to high risk prostate can-cer. J Urol 2016; 195: 1436-43.

33) Maurer T, Weirich G, Schottelius M, et al. Prostate-specific membrane antigen-radio-guided surgery for metastatic lymph nodes in prostate cancer. Eur Urol 2015; 68: 530-4.

34) McCarthy M, Langton T, Kumar D, Campbell A. Comparison of PSMA-HBED and PSMA-I&T as diagnostic agents in prostate carcinoma. Eur J Nucl Med Mol Imaging 2017; 44: 1455-62.