[99cmTc]Tc-PSMA-I&S-SPECT/CT: experience in prostate cancer imaging in an outpatient center.

BACKGROUND: Prostate-specific membrane antigen (PSMA) SPECT imaging in prostate cancer (PCa) could be a valuable alternative in regions where access to PSMA-PET imaging is restricted. [99mTc]Tc-PSMA-I&S is a new 99mTc-labeled PSMA-targeting SPECT agent, initially developed for radio-guided surgery. We report on the diagnostic use of [99mTc]Tc-PSMA-I&S-SPECT/CT in PCa. RESULTS: [99mTc]Tc-PSMA-I&S-SPECT/CT was performed and evaluated in 210 outpatients with PCa at a single center. Patients were imaged for biochemical recurrence (BCR, n = 152, mean PSA 8.7 ng/ml), for primary staging of high-risk PCa (n = 12, mean PSA 393 ng/ml), and restaging in advanced recurrent PCa (n = 46, mean PSA 101.3 ng/ml). Number and location of positive lesions were determined for the different subgroups. For BCR, detection rates were calculated, defined as the proportion of scans with at least one PSMA-positive lesion. PSMA positive lesions were detected in 65.2% of all 210 patients. Tumor tissue was mainly detected in lymph nodes (59%), in the bone (42%), and in the prostate (fossa) (28%). In the subgroup of patients referred for detection of BCR the detection rate increased from 20% at a PSA level < 1 ng/ml to 82.9% and 100% at PSA levels > 4 ng/ml and > 10 ng/ml, respectively. In the subgroup of high-risk patients referred for primary staging, 42% demonstrated metastatic disease. Restaging of advanced recurrent PCa revealed detectability of PSMA positive tumor lesions in 85% of the scans. CONCLUSIONS: [99mTc]Tc-PSMA-I&S-SPECT/CT was useful in PSMA-targeted imaging of PCa at various clinical stages. At low PSA levels (< 4 ng/ml), detection rates of [99mTc]Tc-PSMA-I&S-SPECT/CT in BCR are clearly inferior to data reported for PET-imaging and should thus only be considered for lesion detection if imaging with PET is unavailable. However, at higher PSA levels (> 4 ng/ml) [99mTc]Tc-PSMA-I&S-SPECT/CT provides high detection rates in BCR. [99mTc]Tc-PSMA-I&S-SPECT/CT can also be used for primary staging and for restaging of advanced recurrent PCa. However, further studies are needed to assess the clinical value in these indications.

Influence of localization of PSMA-positive oligo-metastases on efficacy of metastasis-directed external-beam radiotherapy-a multicenter retrospective study.

PURPOSE: Approximately 40-70% of biochemically persistent or recurrent prostate cancer (PCa) patients after radical prostatectomy (RPE) are oligo-metastatic in 68gallium-prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET). Those lesions are frequently located outside the prostate bed, and therefore not cured by the current standards of care like external-beam radiotherapy (EBRT) of the prostatic fossa. This retrospective study analyzes the influence of oligo-metastases' site on outcome after metastasis-directed radiotherapy (MDR). METHODS: Retrospectively, 359 patients with PET-positive PCa recurrences after RPE were analyzed. Biochemical recurrence-free survival (BRFS) (prostate-specific antigen (PSA) < post-radiotherapy nadir + 0.2 ng/mL) was assessed using Kaplan-Meier survival and Cox regression analysis. RESULTS: All patients were initially clinically without distant metastases (cM0). Seventy-five patients had local recurrence within the prostatic fossa, 32 patients had pelvic nodal plus local recurrence, 117 patients had pelvic nodal recurrence, 51 patients had paraaortic lymph node metastases with/without locoregional recurrence, and 84 patients had bone or visceral metastases with/without locoregional recurrence. Median PSA before MDR was 1.2 ng/mL (range, 0.04-47.5). Additive androgen deprivation therapy (ADT) was given in 35% (125/359) of patients. Median PSA nadir after MDR was 0.23 ng/mL (range, < 0.03-18.30). After a median follow-up of 16 months (1-57), 239/351 (68%) patients had no biochemical recurrence. Patients with distant lymph node and/or distant metastases, the so-called oligo-body cohort, had an overall in-field control of 90/98 (91%) but at the same time, an ex-field progress of 44/96 (46%). In comparison, an ex-field progress was detected in 28/154 (18%) patients with local and/or pelvic nodal recurrence (oligo-pelvis group). Compared with the oligo-pelvis group, there was a significantly lower BRFS in oligo-body patients at the last follow-up. CONCLUSION: Overall, BRFS was dependent on patterns of metastatic disease. Thus, MDR of PSMA PET-positive oligo-metastases can be offered considering that about one-third of the patients progressed within a median follow-up of 16 months.

[PSA increase after definitive treatment]. / PSA-Anstieg nach definitiver Therapie.

Following definitive treatment with curative intent a subset of patients with prostate cancer experience biochemical recurrence. In these patients clinical parameters are mostly used to decide if a local or systemic disease recurrence is present. While salvage radiation treatment is advocated for local recurrence after radical prostatectomy, no standard recommendations exist in cases of local recurrence after primary radiation therapy although salvage prostatectomy may be considered. Imaging procedures have traditionally not routinely been recommended for the onset of prostate-specific antigen (PSA) relapse; however, prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT) exhibits high detection rates even at low PSA values. Thus, the current German guidelines state that PSMA PET/CT can be considered if this could result in a decisive change in further treatment management. Currently, a positive influence on oncological long-term outcome, however, has not yet been proven.

Three-dimensional fat-saturated T1-weighted Cartesian volumetric interpolated breath-hold examination (VIBE) for the diagnosis of aortitis in patients with suspected large vessel vasculitis: a comparative study with 18F-FDG PET applying fully integrated PET/MRI.

AIM: To evaluate the feasibility of T1-weighted (T1W) three-dimensional (3D) fat saturated Cartesian volumetric interpolated breath-hold examination (VIBE) magnetic resonance imaging (MRI) sequence for the diagnosis of aortitis in patients with suspected large vessel vasculitis (LVV) applying fully integrated 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/MRI. MATERIAL AND METHODS: Fourteen patients with aortitis and 14 patients with a negative study for aortitis using 18F-FDG PET as the standard of reference for the evaluation of inflammatory aortic involvement were included retrospectively. All patients were imaged at 3 T using T1W VIBE pre- and post-contrast. Four aortic segments were evaluated for image quality (IQ), diagnostic confidence (DC), and the degree of inflammatory activity (IA) using a Likert scale. Binomial and generalised estimating equation model tests were used to assess the diagnostic performance of T1W VIBE. Cohen's k was applied to test for interobserver reproducibility with respect to IA. Spearman's rank correlation coefficient was calculated to examine correlations between IQ, DC, IA, and PET results. RESULTS: On a patient- and segment-based analysis, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 85.7% and 59.8%, 100% and 100%, 100% and 100%, 87.5% and 68%, and 92.9% and 82.1%, respectively. IQ and DC were acceptable to good in all examinations and substantial interobserver agreement was observed for IA (Cohen's k = 0.69). IQ and DC as well as IA and 18F-FDG vessel wall uptake were significantly correlated (r=0.763 and 0.679, respectively; p<0.0001). CONCLUSION: T1W 3D fat saturated VIBE MRI allows diagnosis of aortitis and may aid in the management of patients with suspected LVV.

Impact of 68Ga-PSMA-PET imaging on target volume definition and guidelines in radiation oncology - a patterns of failure analysis in patients with primary diagnosis of prostate cancer.

BACKGROUND: 68Ga-PSMA-PET-imaging has proven to be a highly sensitive and specific diagnostic element for patients with prostate cancer (PC). Does the standard clinical target volume (CTV) cover the majority of 68Ga-PSMA-PET detected lymph nodes (LNs) in a primary setting? METHODS: 25 out of 159 patients with primary PC who underwent 68Ga-PSMA-PET-imaging were analyzed in the process of this study. These 25 high-risk patients had a total of 126 LNs with positive 68Ga-PSMA-ligand uptake. A standard CTV according to the 'Radiation Therapy Oncology Group' consensus was delineated and LNs were judged whether they were in- or outside of this target volume. With a Pearson correlation we additionally evaluated whether the Gleason score, the prostate-specific antigen (PSA) value or the risk according to the Roach formula correlate with a higher chance of LNs being outside of the CTV in uncommon LN locations. RESULTS: 81 (64.3%) of 126 LNs were covered by the CTV with a complete coverage of all positive LNs inside the respective radiation volume in 11 of 25 patients (44%). LNs that were not covered by the CTV included (para-aortic,) common-iliac, pre-sacral, obturatoric, para-rectal, para-vesical and pre-acetabular locations. In a statistical analysis neither the Gleason score, nor the PSA value, nor the calculated risk with the Roach formula correlated with LNs being inside or outside of the CTV in this patient group. CONCLUSION: 68Ga-PSMA-PET-imaging proves to be a valuable asset for patients and physicians for primary diagnosis and treatment planning. In our study, trusting the RTOG consensus for CTV delineation would have led to up to 35.7% of all LNs not to be included in the clinical radiation volume, which might have resulted in insufficient radiation dose coverage.

[PSMA-radioguided surgery in localised recurrent prostate cancer]. / "PSMA-radioguided surgery" beim lokalisierten Prostatakarzinomrezidiv.

Recently, prostate-specific membrane antigen radioguided surgery (PSMA-RGS) was introduced for targeted resection of localised prostate cancer recurrence. Preliminary results show that PSMA-RGS is very sensitive and specific in tracking suspicious lesions intraoperatively. Prerequisite for PSMA-RGS is a positive 68Ga-PSMA positron emission tomography (PET) scan with a preferably singular soft tissue or lymph node recurrence. The first 63 patients treated with PSMA-RGS were analyzed. The extracorporal analysis of a total of 277 tissue specimens yielded the following test quality criteria regarding the presence of malignant tissue: sensitivity 86.2%, specificity 96.4%, positive predictive value 94%, negative predictive value 91.5%. Oncological follow-up data was available from 59 patients. There was a drop in PSA (prostate specific antigen) below 0.2 ng/ml in 38 patients (67%). Of these 38 patients, 17 (45%) are free of biochemical recurrence after a median follow-up of 12.3 months (6.7-31.9 months). Clavien-Dindo grade III complications occurred in 6 of 63 patients (9.5%). In summary, PSMA-RGS proved to be of high value in patients with localised prostate cancer recurrence for exact localisation and resection of oftentimes small metastatic tissue using intraoperative and ex vivo gamma-probe measurements. Furthermore, PSMA-RGS has the potential to positively influence oncological outcomes. However, patient identification on the basis of 68Ga-PSMA PET imaging and clinical parameters is crucial to obtain satisfactory results.

[PET-CT and PET-MRI of the prostate : From 18F-FDG to 68Ga-PSMA]. / PET-CT/-MRT der Prostata : Von 18F-FDG zu 68Ga-PSMA.

CLINICAL/METHODICAL ISSUE: In the last few years nuclear medical diagnostics have experienced a unprecedented renaissance in the diagnostics of prostate cancer, due to the availability of hybrid imaging with positron emission tomography computed tomography (PET/CT), PET magnetic resonance imaging (PET/MRI) and single photon emission computed tomography (SPECT) CT as well as the development of prostate-specific radiopharmaceuticals. METHODICAL INNOVATIONS: The use of fluorodeoxyglucose (FDG), which has been successfully implemented for many years in PET diagnostics, is only helpful in dedifferentiated tumors due to the biological characteristics of prostate cancer. New specific radiopharmaceuticals, such as choline-derivatives, which are incorporated into the prostate cancer cell and built into the cell membrane as well as the recently developed highly specific ligands for prostate-specific membrane antigen (PSMA) are revolutionizing prostate cancer imaging and (re-) staging. PRACTICAL RECOMMENDATIONS: The 68 Ga-labeled PSMA ligands for PET-CT and PET-MRI are highly specific tracers for primary diagnostics and detection of metastases of prostate carcinoma. In risk patients, which includes patients with intermediate and high-risk tumors, they have largely replaced choline-based PET-CT, especially in the case of very low PSA values <0.5 ng/ml in the diagnostics of recurrence. The use in the primary diagnostics as PET-MRI, also in combination with multiparametric MRI (mpMRI), is promising with respect to early diagnostics and image fusion-assisted biopsy as well as surgery and irradiation planning.

Patterns of failure after radical prostatectomy in prostate cancer - implications for radiation therapy planning after 68Ga-PSMA-PET imaging.

BACKGROUND: Salvage radiotherapy (SRT) after radical prostatectomy (RPE) and lymphadenectomy (LAE) is the appropriate radiotherapy option for patients with persistent/ recurrent prostate cancer (PC). 68Ga-PSMA-PET imaging has been shown to accurately detect PC lesions in a primary setting as well as for local recurrence or for lymph node (LN) metastases. OBJECTIVE: In this study we evaluated the patterns of recurrence after RPE in patients with PC, putting a highlight on the differentiation between sites that would have been covered by a standard radiation therapy (RT) field in consensus after the RTOG consensus and others that would have not. METHODS AND MATERIALS: Thirty-one out of 83 patients (37%) with high-risk PC were the subject of our study. Information from 68Ga-PSMA-PET imaging was used to individualize treatment plans to include suspicious lesions as well as possibly boost sites with tracer uptake in LN or the prostate bed. For evaluation, 68Ga-PSMA-PET-positive LN were contoured in a patient dataset with a standard lymph drainage (RTOG consensus on CTV definition of pelvic lymph nodes) radiation field depicting color-coded nodes that would have been infield or outfield of that standard lymph drainage field and thereby visualizing typical patterns of failure of a "blind" radiation therapy after RPE and LAE. RESULTS: Compared to negative conventional imaging (CT/MRI), lesions suspicious for PC were detected in 27/31 cases (87.1%) by 68Ga-PSMA-PET imaging, which resulted in changes to the radiation concept. There were 16/31 patients (51.6%) that received a simultaneous integrated boost (SIB) to a subarea of the prostate bed (in only three cases this dose escalation would have been planned without the additional knowledge of 68Ga-PSMA-PET imaging) and 18/31 (58.1%) to uncommon (namely presacral, paravesical, pararectal, preacetabular and obturatoric) LN sites. Furthermore, 14 patients (45.2%) had a changed TNM staging result by means of 68Ga-PSMA-PET imaging. CONCLUSION: Compared to conventional CT or MRI staging, 68Ga-PSMA-PET imaging detects more PC lesions and, thus, significantly influences radiation planning in recurrent prostate cancer patients enabling individually tailored treatment.

[Bone-specific therapy with radium-223 dichloride : Castration-resistant prostate cancer with symptomatic bone metastases]. / Knochenspezifische Radium-223-Dichlorid-Therapie : Symptomatisches, ossär metastasiertes, kastrationsresistentes Prostatakarzinom.

Radium-223 dichloride (Xofigo®, Alpharadin) is approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. As a calcium mimetic, it is integrated into osteoplastic bone lesions and emits alpha particles with high energy which leads to local destruction of tumor cells. In the 2013 published ALSYMPCA trial, a significant advantage for overall survival and quality of life in comparison to placebo was found. Recent data suggest an increased potential in combination with next generation hormonal treatment.

[Significance of PSMA imaging in prostate cancer]. / Stellenwert der PSMA-Liganden-Bildgebung beim Prostatakarzinom.

BACKGROUND: Prostate cancer (PCa) is one of the most common malignancies of men in developed countries. To improve clinical diagnostics of PCa, 68Ga-PSMA-11 was recently introduced as a new PET tracer. 68Ga-PSMA-11 is able to specifically bind to the prostate-specific membrane antigen (PSMA), which is upregulated on the surface of prostate cancer cells in most patients. OBJECTIVES: To analyse the current significance of 68Ga-PSMA-11 PET imaging in prostate cancer in relation to staging of men with initial diagnosis, biochemical recurrence and metastatic disease. MATERIALS AND METHODS: Retrospective analysis of current literature (PubMed search) regarding 68Ga-PSMA-11 PET diagnostics in primary staging, in biochemical recurrence and in metastasized disease. RESULTS: Compared to conventional imaging, 68Ga-PSMA-11 PET/CT reaches a higher sensitivity with an excellent specificity in the clinical diagnosis of primary staging as well as staging for recurrence and advanced, metastasized disease. In biochemical recurrence, 68Ga-PSMA-11 PET/CT shows significantly higher detection rates in comparison to choline PET/CT, especially in patients with low PSA values. In the clinical diagnosis of recurrent disease, therapy concepts were changed in more than a quarter of the patients due to the use of 68Ga-PSMA-11 PET/CT. The significance of staging with 68Ga-PSMA-11 PET/CT in advanced metastasized patients remains uncertain. CONCLUSIONS: Due to the excellent results of 68Ga-PSMA-11 PET imaging, even in patients with slightly elevated PSA levels, it will continue to play an important role in clinical diagnostics of prostate cancer and, thus, its clinical utilization will become more widely spread.

[PSMA-radioguided surgery in localized recurrent prostate cancer : Current and future aspects]. / "PSMA-radioguided surgery" beim lokal begrenzten Prostatakarzinomrezidiv : Aktueller Stand und zukünftige Entwicklungen.

Recently, PSMA-radioguided surgery (PSMA-RGS) was introduced for targeted resection of localized prostate cancer recurrence. Prerequisite for preoperative patient selection and localization of tumor recurrence is a positive 68Ga-HBED-CC PSMA positron emission tomography (PET) scan with preferably only singular soft tissue or lymph node recurrence. After injection of In-PSMA I&T or Tc-PSMA-I&S single photon emission computer tomography (SPECT)/computer tomography (CT) examination is performed in every patient to verify radiotracer uptake in tumor lesions. In a preliminary study, 111In-PSMA I&T SPECT/CT could detect about half of the 68Ga-HBED-CC PSMA PET-positive lesions, while nearly all PET-positive lesions could be detected using PSMA-RGS and also five additional lesions compared to 68Ga-HBED-CC-PSMA PET. Follow-up data from 55 patients show a PSA reduction >50% and >90% in 44 (80%) and 29 (53%) patients, respectively. In 34 (62%) patients, a PSA drop to <0.2 ng/ml was observed. In all, 15 (27%) patients received further PC-specific treatment; the remaining 40 (73%) patients did not undergo further treatment. In 33% of patients, surgery-related complications were noted; however, most were regarded as minor. Thus, PSMA-RGS seems to be of high value in patients with localized prostate cancer recurrence with exact localization and resection of metastatic tissue. However, patient selection based on 68Ga-PSMA PET imaging and clinical parameters is crucial to obtain satisfactory oncological results.

[PSMA-targeted radioligand therapy in prostate cancer]. / Radionuklidtherapie des Prostatakarzinoms mittels PSMA-Lutetium.

Radioligand therapy (RLT) directed against prostate-specific membrane antigen (PSMA) enables tumor-specific treatment directed against PSMA-overexpressing prostate cancer cells. Several PSMA ligands such as PSMA-617 or PSMA-I&T have been developed that can be labeled with ß­radiating lutetium-177. These are currently applied in compassionate use programs to treat metastatic castration-resistant prostate cancer (mCRPC). PSMA-directed RLT is currently being offered in several nuclear medicine departments throughout Germany. Several retrospective case series demonstrate its activity with a prostate-specific antigen (PSA) decrease >50% in 30-60% of mCRPC patients. The toxicity seems to be low. Hematologic grade 4 toxicity has not been observed and grade 3 toxicities rarely occur. The main nonhematologic adverse events are intermittent dry mouth because of unspecific PSMA expression in the salivary glands as well as fatigue and nausea. Currently there are no prospective studies available for evaluation of PSMA-targeted RLT and a survival benefit over approved standard therapies such as abiraterone, enzalutamide, radium-223-dichloride, docetaxel or cabazitaxel has not been shown. PSMA-targeted RLT should therefore currently only be offered after critical evaluation in patients who exhausted the approved standard therapies.

[Rectal mucosa metastasis in recurrent prostate cancer : (68)Ga-PSMA-PET/CT allows targeted salvage radiotherapy]. / Rektummukosametastase beim Prostatakarzinomrezidiv : (68)Ga-PSMA-PET/CT ermöglicht eine gezielte Salvagestrahlentherapie.

This article presents for the first time a case of rectal mucosa metastasis of recurrent prostate cancer that was diagnosed with (68)Ga-PSMA PET/CT. After histological confirmation, the patient was treated with salvage radiotherapy. This case report underlines the specificity and efficacy of PSMA-based PET imaging. In case of biochemical relapse, it can be used even at low PSA levels to detect prostate cancer metastases that might also be in atypical locations. Thus, (68)Ga-PSMA PET/CT may allow new options for salvage therapy.

[Will 68Ga-PSMA PET become the New Imaging Standard for Prostate Cancer?]. / 68Ga-PSMA PET auf dem Weg zur neuen Standardbildgebung bei Prostatakarzinom?

This article describes the current knowledge in prostate cancer imaging with (68)Ga-PSMA PET, which achieves excellent specificities and higher sensitivities compared with standard imaging for local tumour detection as well as primary and recurrence staging. Therefore, (68)Ga-PSMA PET will probably play an increasing role for the diagnostic investigation of prostate cancer and will be more widely used in the future.

[Combined PET-MRI of the abdomen]. / Kombinierte PET-MRT des Abdomens.

The first fully integrated combined positron emission tomography-magnetic resonance imaging (PET-MRI) scanners have been clinically available since 2010. Large prospective studies regarding indications and diagnostic accuracy of this new modality are not yet available; however, preliminary studies have shown a higher diagnostic accuracy and confidence compared to PET-computed tomography (PET-CT) in regions where MRI is known to be superior to CT, such as the liver. The benefit of MRI in accurate lesion characterization and the additional value of diffusion-weighted imaging (DWI) as a complementary functional modality by means of the apparent diffusion coefficient (ADC) is apparent in entities with low tracer uptake (e.g. due to small size) and a decreased or absent accumulation pattern on PET.

Loco-regional recurrence after surgical treatment of oral squamous cell carcinoma: Proposals for follow-up imaging based on literature, national guidelines and institutional experience.

The recurrence rate following the treatment of oral squamous cell carcinoma (OSCC) by primary surgery is about 10%-26%. The earliest possible diagnosis of residual tumour, recurrence of local tumour disease, and subsequent metastasis is essential for an improvement of the overall survival and of the survival period for affected patients. No international consensus exists for a post-therapeutic surveillance schedule for OSCCs. Based on a review of the literature, existing guidelines, and our institutional experience, we have established an algorithm for the follow-up of these patients regarding the timing and techniques of postoperative imaging. We recommend a follow-up interval of 6 weeks during the first half-year after discharge from hospital by single clinical and alternating clinical check-ups combined with computed tomography (CT) or magnetic resonance imaging (MRI), followed by an interval of 3 months in the second half-year, with clinical and radiological check-ups. In year 2, we recommend a follow-up interval of 3 months with single clinical and alternating clinical check-ups combined with CT or MRI. In year 3, we recommend screening every 6 months, both clinically and via imaging, because of the decreased risk of recurrence. From year 5 onwards, our recommendation is a clinical and imaging-based examination every 6-12 months, depending on patient risk factors and disease progression. Four standard imaging techniques, namely positron emission tomography (PET), CT, MRI, and ultrasound (US), are discussed concerning their range of application, sensitivity, and specificity. Furthermore, the technical aspects of our institutional protocols are described in detail. In highly frequented head and neck cancer centres, PET and US are of secondary importance, since CT and MRI are nowadays highly efficient tools in primary diagnostic and post-therapeutic surveillance.