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The successful use of theranostic twins in neuroendocrine tumors (NET) is the pioneering approach to radionuclide therapy in other tumor types. 64Cu/18F PSMA for molecular imaging with PET-CT and peptide radioligand therapy (PRLT) with 177Lu labeled PSMA inhibitors are the next theranostic twins in nuclear medicine. 68Ga/ 64Cu/18F PSMA PET-CT detects metastatic prostate cancer with high diagnostic sensitivity and specificity and can be used to select patients for PRLT and evaluate therapy response. Radionuclide therapy with 177Lu-PSMA inhibitors has been shown to be effective in the treatment of metastatic CRPC.

Aim: PSMA expression has been observed in increased levels in patients with high Gleason scores. Current information on Ga-68 PSMA PET/CT shows that primary staging with PET/CT is important in patients with high-risk PC. Ga-68 PSMA PET/CT may also have a place in patients with intermediate risk PC, but only a few data are available at present. In this study, we aimed to elucidate the relationship between PSMA expression value in the prostate gland, total PSA levels and GS in patients diagnosed with prostate cancer. Material and Method: A total of 98 patients who were pathologically diagnosed with prostate cancer that did not receive any treatment and underwent Ga‐68 PSMA PET/CT imaging for staging were included in the study. Findings detected in Ga‐68 PSMA PET/CT imaging were categorized as prostate, lymph node, bone, and visceral organ. The focal increased PSMA expression values ​​observed in the prostate gland were recorded as SUVmax. The patients were divided into two separate groups according to their GS score (GS>7 and GS≤7). Correlations between prostate PSMA SUVmax, GS score and total PSA scores were investigated. Results: PSMA SUVmax levels of the group with a Gleason score of >7 were found to be significantly higher than the group with a Gleason score of ≤7 (p=0.03). The rates of lymph node metastasis, bone metastasis and visceral organ metastases were found to be significantly higher in the group with a Gleason score >7 compared to the group with a Gleason score ≤7. A positive correlation was observed between PSMA SUVmax and Total PSA (r=0.260, p=0.01). A positive correlation was observed between PSMA SUVmax and Gleason score (r=0.260, p=0.01). A positive correlation was observed between total PSA and Gleason score (r=0.320, p=0.001). Conclusion: In conclusion, PSMA SUVmax and Total PSA levels were higher in the group with high Gleason score. There is a positive correlation between PSMA SUVmax and total PSA. Clinicians should be careful in this regard, as the possibility of metastasis will be high in groups with high Gleason scores.

PURPOSE Isolated case reports mention the uptake of radiolabeled PSMA in lymphoma. However, it is not clear if the intensity of 68Ga-PSMA expression varies among different histological subtypes or if it correlates with 18F-FDG uptake. This study compared both tracers in patients with diverse lymphoma subtypes. METHODS Ten patients with biopsy-proven-lymphoma underwent 18F-FDG and 68Ga-PSMA-PET/CT (maximum time interval: 6 days). Lymphoma subtypes included Hodgkin's lymphoma (HL, three patients) and aggressive and indolent non-Hodgkin's lymphoma (NHL, seven patients). The intensity of PSMA uptake was classified visually as low, intermediate, or high, using blood pool, liver and parotid gland uptake as references. Maximum standardized-uptake value (SUVmax) of each affected site was measured in both sets of images. RESULTS FDG detected 59/59 involved sites in 10 patients and PSMA 47/59 sites in nine patients. PSMA uptake was generally low, regardless of the intensity of FDG uptake, but it was classified as intermediate in two patients. The median SUVmax varied from 2.0 (2.0-8.2) to 30.9 for FDG and from 1.7 (1.7-1.7) to 4.4 for PSMA, P < 0.0001. The primary lesion of one patient had a marked intralesional mismatch uptake pattern of the tracers, with areas of higher PSMA expression than FDG uptake, and vice-versa. A brain lesion was more easily identified with PSMA than with FDG images. CONCLUSION HL and several NHL subtypes may present PSMA uptake. The intensity of PSMA expression is generally lower than that of FDG uptake and seems to present less variation among the different histological subtypes of lymphomas.

OBJECTIVE The aim of this study was to evaluate the relationship between volumetric parameters calculated using semiautomatic quantification of lesions detected in 68Ga-labeled prostate-specific membrane antigen PET-computed tomography (68Ga-PSMA PET/CT) and clinical characteristics in prostate cancer (PCa) patients with biochemical recurrence. METHODS A total of 85 consecutive PCa patients with biochemical recurrence who underwent 68Ga-PSMA PET/CT at our institution from January 2019 to March 2020 were retrospectively assessed. 68Ga-PSMA PET/CT-derived volumetric parameters, including whole-body PSMA tumor volume (wbPSMA-TV) and whole-body total lesion PSMA (wbTL-PSMA), as well as the established maximum and mean standardized uptake value (SUVmax and SUVmean), were calculated for each patient. All PET-derived parameters were analyzed for correlation with prostate-specific antigen (PSA) levels and for association with Gleason scores. RESULTS Eighty-five patients with a mean age of 68.9 ± 7.8 years (range, 47-83 years) and a mean PSA level of 40.9 ± 92.1 ng/ml (range, 0.2-533.2 ng/ml) were analyzed. Volumetric parameters, that is, wbPSMA-TV and wbTL-PSMA, demonstrated a statistically significant correlation with PSA levels (r = 0.403 and r = 0.556, respectively, all at P < 0.001) and only the means of wbTL-PSMA were significantly different between the Gleason score groups (P < 0.05). CONCLUSIONS The results of our study indicate that 68Ga-PSMA PET/CT might be a valuable tool for the detection and follow-up of recurrence in PCa patients. 68Ga-PSMA PET/CT-derived quantitative volumetric parameters demonstrated a highly significant correlation with changes in PSA levels. Larger prospective studies are needed to help reveal the full potential of parameters such as PSMA-TV and TL-PSMA derived from PET imaging with 68Ga-PSMA.

OBJECTIVE 68Ga-PSMA-PET/CT is a relatively new technique, that is rapidly becoming widespread. We aimed to contribute interobserver-intraobserver agreement of 68Ga-PSMA-PET/CT, among low/high-experienced interpreters. METHODS 68Ga-PSMA-PET/CT of 56 patients with prostate cancer were evaluated blindly by four observers. Visual interpretation of malignant disease and SUVmax for lymph node (LN) regions, local tumor, bones and visceral organs were recorded. Cohen's Kappa and Fleiss' Kappa analyses were used to measure agreement between low/high/all-experienced observers. Variations were compared for regions, and the effect of prostate-specific antigen or Gleason score on the results was investigated. RESULTS Interobserver agreement was almost perfect for all LN regions (LN1 low-experienced κ: 0.84/0.84, high-experienced 0.89/0.96; LN2 low-experienced κ: 0.88/0.79, high-experienced 0.95/0.95; LN3 low-experienced κ: 0.84/0.89, high-experienced 0.87/0.94, first/second readings, respectively) and bone lesions (low-experienced κ: 0.88/0.88, high-experienced 0.92/0.92, first/second readings, respectively). For local tumor, interobserver agreement was substantially-almost perfect among a high-experienced group (κ: 0.74/0.89, first/second readings, respectively), and was moderate-substantial among a low-experienced group (κ: 0.62/0.56, first/second readings, respectively). Intraobserver agreement was almost perfect for three observers for all regions and substantial for the observer with the lowest experience in LN3, local and visceral lesions (κ: 0.74/0.79/0.62, respectively). CONCLUSION Interpretation of prostate-specific membrane antigen (PSMA) for prostate cancer is acceptably consistent among observers, but some details are noteworthy. The evaluation should be done more algorithmically for local tumors, since all observers showed relatively lower agreement. The agreement increased as prostate-specific antigen and Gleason score increased. The observer with PSMA experience

Objectives To develop and examine a scoring system in metastatic castration-resistant prostate carcinoma (mCRPC) that integrates findings of both 68Ga-prostate-specific membrane antigen (PSMA) and flurodeoxyglucose (FDG) PET-CT imaging in a single combined parameter and referred to as the 'Pro-PET' score. Methods A six-tier integrated dual tracer PET-CT (68Ga-PSMA and FDG) Image Scoring System ('Pro-PET' score) was conceptualized, based on the findings of both 68Ga-PSMA-11 and FDG PET-CT in patients of mCRPC. This proposed integrated scoring was examined in a retrospective analytical study assessing mCRPC patients (n = 47) referred for 177Lu-PSMA-617 peptide receptor radioligand therapy (PRLT) and had both FDG and 68Ga-PSMA PET-CT undertaken within 15 days of each other without any interim treatment intervention. The 'Pro-PET' score grades and subgrades were assigned and compared with clinical data, such as histopathology, Gleason score, serum prostate-specific antigen (PSA), treatment response (symptomatic, biochemical, metabolic and anatomical) and survival [overall survival (OS) and progression-free survival (PFS)]. Results The Pro-PET score significantly correlated with symptomatic (P = 0.05), biochemical (P = 0.05), metabolic (P = 0.001) and anatomical (P = 0.012) responses, PFS (P = 0.03) and OS (P = 0.027). On multivariate analysis, histopathology, Gleason score and PSA as individual parameters were not significantly associated with OS and PFS, whereas the Pro-PET score was found to have a significant association (P = 0.001 for PFS and 0.011 for OS). Conclusion The 'Pro-PET' scoring system integrating dual tracer PET-CT imaging findings in a single parameter appeared as a potentially promising prognostic marker that has the potential to enhance the objectivity and scientific basis of prostate carcinoma theranostics and prognostication.

A 43-year-old man diagnosed with fibrous dysplasia with McCune-Albright syndrome was subjected to 18F-fluoride bone scan and 68Ga-PSMA-HBED-CC PET/CT as per the institution protocol. 18F-bone scan revealed extensive involvement of axial and appendicular skeleton confirming polyostotic fibrous dysplasia. 68Ga-PSMA PET/CT showed increased tracer uptake in corresponding lesions of fibrous dysplasia. PSMA uptake in fibrous dysplasia lesions has been rarely described with literature evidence being limited to anecdotal case reports. Nevertheless, due to increasing use of PSMA PET/CT, one should be aware of this false-positive finding to avoid misinterpretation of the scans.

Background 99mTc-prostate-specific membrane antigen (PSMA) SPECT/CT is less expensive and readily available modality compared with 68Ga-PSMA PET/CT for imaging prostate cancer (PC). The aim of this study is to compare the value of these 2 modalities in patients confirmed or suspicious to have metastatic prostate cancer. Patients and methods Twenty-two patients with the mean age of 66.6 ± 10.1 years were studied using 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT, with less than 7 days interval between the 2 imaging procedures. Whole-body PET/CT was done 60 minutes after IV injection of 185 MBq (5 mCi) of 68Ga-PSMA. 99mTc-PSMA SPECT/CT was performed 3 hours after IV injection of 555 to 740 MBq (15-20 mCi) of 99mTc-PSMA. The images of each modality were interpreted independently, and the results were compared according to patient-based as well as region-based analyses. Results In patient-based evaluation, both 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT scans were positive in 95.45% (21/22). In region-based evaluation, 68Ga-PSMA PET/CT detected 53 regions (median of 2 regions per patient; range, 0-5), whereas 43 (median of 2 regions per patient; range, 0-5) were detected by 99mTc-PSMA SPECT/CT. Most of these differences could be explained by lower detection rate of 99mTc-PSMA SPECT/CT in prostate bed (n = 6). PET/CT detected more involved regions than SPECT/CT (P = 0.007), whereas similar frequency of extraprostatic lesions were diagnosed in both modalities (P = 0.102). Significant correlation was also demonstrated between serum prostate-specific antigen level and imaging parameters of disease extension detected by 2 modalities. Conclusions 99mTc-PSMA SPECT/CT could be a potential substitute for 68Ga-PSMA PET/CT in high-risk patients, except when evaluation of prostate bed is of major concern.

Contains fulltext : 235315.pdf (Publisher’s version ) (Closed access) PURPOSE: This study proposes optimal tracer-specific threshold-based window levels for PSMA PET-based intraprostatic gross tumour volume (GTV) contouring to reduce interobserver delineation variability. METHODS: Nine (68)Ga-PSMA-11 and nine (18)F-PSMA-1007 PET scans including GTV delineations of four expert teams (GTV(manual)) and a majority-voted GTV (GTV(majority)) were assessed with respect to a registered histopathological GTV (GTV(histo)) as the gold standard reference. The standard uptake values (SUVs) per voxel were converted to a percentage (SUV%) relative to the SUV(max). The statistically optimised SUV% threshold (SOST) was defined as those that maximises accuracy for threshold-based contouring. A leave-one-out cross-validation receiver operating characteristic (ROC) curve analysis was performed to determine the SOST for each tracer. The SOST analysis was performed twice, first using the GTV(histo) contour as training structure (GTV(SOST-H)) and second using the GTV(majority) contour as training structure (GTV(SOST-MA)) to correct for any limited misregistration. The accuracy of both GTV(SOST-H) and GTV(SOST-MA) was calculated relative to GTV(histo) in the 'leave-one-out' patient of each fold and compared with the accuracy of GTV(manual). RESULTS: ROC curve analysis for (68)Ga-PSMA-11 PET revealed a median threshold of 25 SUV% (range, 22-27 SUV%) and 41 SUV% (40-43 SUV%) for GTV(SOST-H) and GTV(SOST-MA), respectively. For (18)F-PSMA-1007 PET, a median threshold of 42 SUV% (39-45 SUV%) for GTV(SOST-H) and 44 SUV% (42-45 SUV%) for GTV(SOST-MA) was found. A significant pairwise difference was observed when comparing the accuracy of the GTV(SOST-H) contours with the median accuracy of the GTV(manual) contours (median, - 2.5%; IQR, - 26.5-0.2%; p = 0.020), whereas no significant pairwise difference was found for the GTV(SOST-MA) contours (median, - 0.3%; IQR, - 4.4-0.6%; p = 0.199). CONCLUSIONS: Threshold-based contouring using GTV(majority)-trained SOSTs achieves an accuracy comparable with manual contours in delineating GTV(histo). The median SOSTs of 41 SUV% for (68)Ga-PSMA-11 PET and 44 SUV% for (18)F-PSMA-1007 PET form a base for tracer-specific window levelling. TRIAL REGISTRATION: Clinicaltrials.gov ; NCT03327675; 31-10-2017.

Purpose Currently, approximately 11–38% of prostate cancer (PCa) patients undergoing radical prostatectomy have a positive surgical margin (PSM) on histopathology. Cerenkov luminescence imaging (CLI) using 68Ga-prostate-specific membrane antigen (68Ga-PSMA) is a novel technique for intraoperative margin assessment. The aim of this first-in-man study was to investigate the feasibility of intraoperative 68Ga-PSMA CLI. In this study, feasibility was defined as the ability to distinguish between a positive and negative surgical margin, imaging within 45 min and low radiation exposure to staff. Methods Six patients were included in this ongoing study. Following perioperative i.v. injection of ~ 100 MBq 68Ga-PSMA, the prostate was excised and immediately imaged ex vivo. Different acquisition protocols were tested, and hotspots on CLI images from the intact prostate were marked for comparison with histopathology. Results By using an acquisition protocol with 150 s exposure time, 8 × 8 binning and a 550 nm shortpass filter, PSMs and negative surgical margins (NSMs) were visually correctly identified on CLI in 3 of the 5 patients. Two patients had a hotspot on CLI from cancer Conclusion Overall, the study showed that 68Ga-PSMA CLI is a feasible and low-risk technique for intraoperative margin assessment in PCa. The remaining patients in this ongoing study will be used to assess the diagnostic accuracy of the technique. Trial registration: NL8256 registered at www.trialregister.nl on 04/11/20109.

We developed a model predicting the probability of detecting prostate cancer recurrence outside the prostatic fossa on prostate specific membrane antigen positron emission tomography/computerized tomography in patients with biochemical recurrence after radical prostatectomy.We retrospectively included 419 consecutive patients with biochemical recurrence (prostate specific antigen less than 2.0 ng/ml) after radical prostatectomy who underwentMedian prostate specific antigen at scanning was 0.40 ng/ml (IQR 0.30-0.70). Overall 174 (42%) patients had prostate cancer recurrence outside the prostatic fossa. Prostate specific antigen at time of scanning, and grade group, N stage and surgical margin status at radical prostatectomy specimen were significant predictors for detecting prostate cancer recurrence outside the prostatic fossa. The bootstrapped AUC of this model was 0.75 (IQR 0.73-0.77). The decision curve analysis showed a net benefit by a model based probability from 16%. Limitations include the retrospective design and the missing histological correlation of positive lesions.Next to the prostate specific antigen at time of scanning, grade group, N stage and surgical margin status at radical prostatectomy specimen are significant predictors for detecting prostate cancer recurrence outside the prostatic fossa on prostate specific membrane antigen positron emission tomography/computerized tomography. The presented model is implemented in a dashboard to assist clinicians in determining the optimal time to perform

We report 3 patients with COVID-19 findings in 68Ga-PSMA PET/CT taken for staging. The first patient, A 64-year-old man with prostate cancer, who had COVID-19 in November 2020 and whose treatment was completed, was observed to continue with COVID-19 findings in 68Ga-PSMA PET/CT in December 2020 before surgery. Other patients were asymptomatic for the disease. It was determined that a PSMA uptake in the lungs corresponding to the CT findings of COVID-19 had increased in 68Ga-PSMA PET/CT.

Objective The aim of this study was to assess the interreader agreement in evaluation 68Ga-prostate-specific membrane antigen (PSMA) PET/CT according to three current criteria European association of nuclear medicine, PROMISE with miTNM, and PSMA-RADS in newly diagnosed prostate cancer (PC) patients. Methods The images of 101 patients who had been diagnosed with PC and underwent Ga-68-PSMA PET/CT at the time of initial staging were evaluated according to the three interpretation criteria by two nuclear medicine specialists. Local tumor, pelvic lymph node metastasis and distant metastasis were evaluated separately. Abdominal lymph nodes, bone and visceral organ metastases were additionally evaluated as subregions of distant metastatic sites. Patients were evaluated in subgroups Gleason score >= 8 or prostate-specific antigen >= 20 ng/mL as the high-risk group (HR) and prostate-specific antigen

Prostate cancer is the second most common cancer in men. Its diagnosis and management are still challenging as both PSA levels and imaging have had their limitations. Prostate specific membrane antigen (PSMA) is aprostate specific cell surface protein and has been emerging as a novel target for PET imaging of prostate cancer. 68Ga PSMA PET-CT imaging have been shown as a better imaging technology in primary prostate cancer and at the same time detecting lymph node and bone metastases even in low PSA levels. Moreover, its counterpart 177 Lu PSMA has a great prospectto be used for the treatment of castration resistantprostate cancer. Bangladesh J. Nuclear Med. 22(1): 53-57, Jan 2019

Meningiomas are typically benign and the most common primary brain tumors. They are usually diagnosed based on their characteristic appearance on both MRI and CT. Meningiomas can easily be misdiagnosed as metastasis of prostate cancer due to their high 68Ga-PSMA uptake on 68Ga-PSMA PET/CT. We present a case of a metastatic prostate adenocarcinoma with PSMA-avid lesion in the right frontal lobe on 68Ga-PSMA PET/CT. Later, MRI confirmed the brain lesion as meningioma.

The aim of the present study is to investigate the synergic role of 68Ga-PSMA PET/MRI and 68Ga-DOTA-RM2 PET/MRI in prostate cancer (PCa) staging. We present pilot data on twenty-two patients with biopsy-proven PCa that underwent 68Ga-PSMA PET/MRI for staging purposes, with 19/22 also undergoing 68Gaa-DOTA-RM2 PET/MRI. TNM classification based on image findings was performed and quantitative imaging parameters were collected for each scan. Furthermore, twelve patients underwent radical prostatectomy with the availability of histological data that were used as the gold standard to validate intraprostatic findings. A DICE score between regions of interest manually segmented on the primary tumour on 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and on T2 MRI was computed. All imaging modalities detected the primary PCa in 18/19 patients, with 68Ga-DOTA-RM2 PET not detecting any lesion in 1/19 patients. In the remaining patients, 68Ga-PSMA and MRI were concordant. Seven patients presented seminal vesicles involvement on MRI, with two of these being also detected by 68Ga-PSMA, and 68Ga-DOTA-RM2 PET being negative. Regarding extraprostatic disease, 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI resulted positive in seven, four and five patients at lymph-nodal level, respectively, and at a bone level in three, zero and one patients, respectively. These preliminary results suggest the potential complementary role of 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI in PCa characterization during the staging phase.

Gallium-68-labeled prostate-specific membrane antigen (68Ga-PSMA), as a relatively new positron emission tomography (PET) radiotracer, can be used to evaluate tumors other than prostate cancer, including renal cell carcinoma and probably non-small cell lung cancer, as discussed in our case. We present the case of a 65-year-old man with a history of lung adenocarcinoma diagnosed in 2015 and a subsequent diagnosis of renal cell carcinoma in 2018, treated with a right lower lobectomy and a left partial nephrectomy, respectively. Both conditions were evaluated using 18F-fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) scan before surgery. A rise in prostate-specific antigen (PSA) was detected in the follow-up in September 2020, and the patient was referred for a 68Ga-PSMA PET/CT scan following pelvic magnetic resonance imaging (MRI). The 68Ga-PSMA PET/CT scan demonstrated avid lesions in both lung and kidney surgical beds. The 68Ga-PSMA PET/CT scan can be potentially used in patients with recurrent renal cell carcinoma to detect metastasis. This modality may also detect non-small cell lung cancer lesions; however, further investigation is needed.

Purpose: The aim of the study was to elaborate the incidence and type of skeletal involvement in a large cohort of patients with newly diagnosed prostate cancer (PCa) referred for Ga-68 PSMA-11 PET/CT staging in a single center.Methods: Study cohort included 963 consecutive patients with newly diagnosed PCa referred Ga-68 PSMA-11 PET/CT study for staging. The incidence of bone involvement, type of bone metastases, extent of disease were determined and correlated with the ISUP Grade Group (GG) criteria, and PSA levels.Results: Bone metastases were found in 188 (19.5%) of 963 patients. Osteoblastic type metastases were the most common type of bone metastases presented in 133 of the patients with malignant bone involvement (70.7%). Slightly more than half of them (54.1%) had "pure" osteoblastic lesions, while the other 45.9% had also intramedullary and/or osteolytic type lesions. Intramedullary metastases were found in 97 patients (51.6%), while 41 (21.8%) of them were "pure" intramedullary lesions. Osteolytic metastases were detected in 36 patients (19.2%), of which 8 were "pure" osteolytic lesions. Bone metastases were found in 10.7% of patients with PSA10 ng/dL; in 6.1% of patients with GG≤2/3 and in 8.9% of patients with GG 4/5. In 7.6% of the patients, skeletal involvement was extensive, while 11.9% of patients had oligometastatic disease.Conclusion: Although traditionally bone metastases of PCa are considered osteoblastic; osteolytic and intramedullary metastases are common, as identified on PET with labeled-PSMA.

Aim Few small-scaled studies performed systematic analysis of the benefits of extending prostate specific membrane antigen positron-emission tomography/ computed tomography (68Ga-PSMA I&T PET/CT) to the lower extremities in prostate cancer (PCa) patients. We hypothesized that 68Ga-PSMA I&T PET/CT positive lesions are rare in lower extremities of prostate cancer (PCa) patients, the clinical implication is negligible and may therefore be omitted. Methods We retrospectively analyzed 1,068 PCa patients who received 68Ga-PSMA I&T PET/CT in a single institution (2016–2018). Of those, 285 (26.7%) were newly diagnosed, 529 (49.5%) had biochemical recurrence (BCR) and 254 (23.8%) were castration-resistant prostate cancer (CRPC) patients. Results Of 1,068 68Ga-PSMA I&T PET/CTs, positive lesions in the lower extremities were identified in 6.9% patients (n=74). Positive lesions in the lower extremities were most common in CRPC patients (19.7%; n=50), followed by newly diagnosed (3.2%; n=9) and BCR (2.8%; n=15) PCa patients. Only 3 patients presented with exclusive lesions in the lower extremities, respectively 0.8% (n=2) in CRPC and 0.4% (n=1) in newly diagnosed PCa. Both CRPC (94.1%, n=47) and BCR (80.0%, n=12) patients with PSMA-positive lesions predominantly received systemic therapy. Conclusion Identification of lower extremities lesions with PSMA PET/CT is uncommon and exclusive lesions are rare. PSMA PET/CT findings of the lower extremities did not change therapy management. Thus, scanning of the lower extremities can be omitted in standard protocols.

We present the case of a 45-year-old woman with known adenoid cystic carcinoma of the right parotid gland, postexcision and postoperative radiation therapy. She was followed up on 18F-FDG PET/CT, which revealed minimal local residual disease and bilateral lung nodules, for which chemotherapy was initiated. Postchemotherapy, 18F-FDG PET/CT showed residual lung metastases. As a part of ongoing project, 68Ga-PSMA PET/CT done revealed additional focal uptake in the right cerebellum, missed on FDG PET/CT. The brain lesion was confirmed upon MRI.

Purpose: The aim of the present study is to investigate the synergic role of 68Ga-PSMA PET/MRI and 68Ga-DOTA-RM2 PET/MRI in PCa staging. Methods: Fifteen patients with biopsy-proven PCa underwent both 68Ga-PSMA PET/MRI and 68Ga-DOTA-RM2 PET/MRI within one month. TNM classification based on image findings was performed and semi-quantitative PET and quantitative MRI parameters were collected for each scan. Finally, DICE score between regions of interest manually segmented on the primary tumor on 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and on T2 MRI was computed. Results: All imaging modalities detected the primary PCa in 15 patients, with slight differences regarding the multifocality of intra-prostatic findings. Two patients presented seminal vesicles involvement on MRI, one of these was also detected by 68Ga-PSMA, with no uptake on 68Ga-DOTA-RM2 images. Regarding extra prostatic disease, 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI resulted positive in 6, 2 and 4 patients at lymph-nodal level, respectively, and at bone level in 2, 0 and 1 patients, respectively, with 68Ga-PSMA PET detecting more lesions compared to 68Ga-DOTA-RM2 PET. The different findings detected by 68Ga-PSMA PET and 68Ga-DOTA-RM2 PET might reflect the complementary role of these radiotracers, as they detected different foci of intraprostatic disease, seminal vesicle invasion, lymph nodal and bone involvement. Conclusion: These preliminary results suggest a synergic role of 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and mpMRI in PCa characterization during the staging phase. (EudraCT: 2018-001034-18)

Objective: To evaluate the effect that external cooling of the salivary glands (ECSG) has on the uptake of gallium-68-labeled prostate-specific membrane antigen (68Ga-PSMA), as an indirect assessment of the capacity of ECSG to reduce the local dose in lutetium-177-PSMA-617 radioligand therapy. Materials and Methods: Ten patients with prostate cancer were submitted to 68Ga-PSMA positron emission tomography/computed tomography with unilateral ECSG. The ECSG was started at 30 min before the injection of the radiotracer and maintained until the end of image acquisition (1 h after injection). Each salivary gland was assessed by determining the maximum, mean, and peak standardized uptake values (SUVmax, SUVmean, and SUVpeak, respectively). The volume of each gland was determined in a volume of interest delineated by a threshold SUVmax of 10%. Paired Student’s t-tests were used in order to compare the results. Results: In terms of the SUV parameters, there were no statistically significant differences between the cooled and contralateral salivary glands. However, the mean volume was 27% lower in the cooled parotid glands than in the contralateral parotid glands (p = 0.004). Conclusion: The use of ECSG does not appear to reduce 68Ga-PSMA uptake by the salivary glands. In addition, there is yet no evidence that ECSG is effective in preventing salivary gland toxicity. Resumo Objetivo: Avaliar o impacto do resfriamento externo de glândulas salivares (REGS) na captação de 68Ga-PSMA como marcador indireto dessa intervenção para redução da dose local na terapia com 177Lu-PSMA. Materiais e Métodos: Dez pacientes com câncer de próstata foram submetidos a PET/CT com 68Ga-PSMA com REGS unilateral. O resfriamento se iniciou 30 minutos antes da injeção do radiofármaco até o fim da aquisição de imagem, 1 hora após a injeção. Cada glândula foi avaliada para os valores de captação padronizados máximo, médio e pico (SUVmáx, SUVmédio e SUVpico, respectivamente). O volume foi definido por um isocontorno usando 10% do SUVmáx. Os resultados foram comparados com o teste t de Student. Resultados: Não houve diferença estatisticamente significante entre os valores de SUV das glândulas resfriadas e seus controles. Houve 27% de redução volumétrica (p = 0,004) nas parótidas resfriadas em comparação ao controle. Conclusão: Não houve redução da captação de 68Ga-PSMA nas glândulas salivares ao REGS. Atualmente não há evidências que suportem essa prática clínica.

PSMA-based nuclear medicine imaging impacts increasingly the clinical decision process in prostate cancer patients. A well-known PSMA pitfall is uptake into autonomic ganglia. The intensity of uptake, the shape, and the exact location of the correlating structure in CT are supposed to aid discriminating between ganglia and lymph node metastases. In this patient, we found intense uptake in a nodular shaped para-aortal soft tissue lesion suspicious of a lymph node metastases at staging as well as restaging. After secondary resection, the lesion was histologically proven an autonomic ganglion with intense PSMA expression.

Two cases with Ga-PSMA-avid prostate cancer recurrence in the vas deferens are presented. These cases highlight the clinical importance of imaging the pattern of local prostate cancer recurrence and the potential difficulties that arise due to the altered anatomy in the prostate bed after prostatectomy or radiotherapy.

Background Detectable uptake of 68Ga-PSMA-ligands in sympathetic ganglia may potentially lead to mistaking them for malignant lesions. Our aim was to investigate the anatomy of cervico-thoracic-ganglia-complex (CTG-C) in the MR part of multimodal 68Ga-PSMA-11 PET/MR imaging, in view of PET factors hindering its proper identification. Patients and methods In 106 patients, 212 sites of the CTG-C were retrospectively reviewed to assess the radiotracer uptake (SUVmax), size, shape, position, symmetry of location and visual uptake intensity. Asymmetry of PSMA-ligand uptake and increased uptake were regarded as risk factors of malignancy. Results In 66.0% left (L) and 53.8% right (R) CTG-C we noticed configurations, resembling the shape of an exclamation-mark, a question-mark, or its part (called “typical”). Tumor-like CTG-C shapes (oval, binodular or longitudinal) were detected in 28.3% L-CTG-C and in 40.6% R-CTG-C. When visual assessment of PET suggested malignancy, the recognition of “typical” shape of underlying CTG-C on MR generated a rise in the accuracy of their proper identification (from 34.4% to 75%, χ2(1) = 70.4; p < 0.001). Recognizing the shape of the CTG-C as “typical” in MR allowed us to classify as “not-suspicious” 61.9% of all CTG-C which were treated as “suspicious” after sole PET assessment. Conclusions The characteristic shape of cervico-thoracic-ganglia-complex (resembling a question-mark, or its part) helps in proper recognition of CTG-C on multimodal whole-body 68Ga-PSMA-ligand PET/MR imaging, when detectable uptake might lead to considering pathology.

OBJECTIVE. The purpose of this study is to provide a concise summary of the current experience with (68)Ga-labeled prostate-specific membrane antigen (PSMA)–11 imaging of prostate and nonprostate malignancies and benign conditions. CONCLUSION. PSMA is overexpressed in prostate cancer and in the neovasculature of many other malignancies. The relevance of PSMA as a biologic target, coupled with advances in the design, synthesis, and evaluation of PSMA-based radionuclides for imaging and therapy, is anticipated to play a major role in patient care.

It has in recent years been reported that microemulsion (ME) delivery systems provide an opportunity to improve the efficacy of a therapeutic agent whilst minimising side effects and also offer the advantage of favourable treatment regimens. The prostate‐specific membrane antigen (PSMA) targeting agents PSMA‐11 and PSMA‐617, which accumulate in prostate tumours, allow for [68Ga]Ga3+‐radiolabelling and positron emission tomography/computed tomography (PET) imaging of PSMA expression in vivo. We herein report the formulation of [68Ga]Ga‐PSMA‐617 into a ME ≤40 nm including its evaluation for improved cellular toxicity and in vivo biodistribution. The [68Ga]Ga‐PSMA‐617‐ME was tested in vitro for its cytotoxicity to HEK293 and PC3 cells. [68Ga]Ga‐PSMA‐617‐ME was administered intravenously in BALB/c mice followed by microPET/computed tomography (CT) imaging and ex vivo biodistribution determination. [68Ga]Ga‐PSMA‐617‐ME indicated negligible cellular toxicity at different concentrations. A statistically higher tolerance towards the [68Ga]Ga‐PSMA‐617‐ME occurred at 0.125 mg/mL by HEK293 cells compared with PC3 cells. The biodistribution in wild‐type BALB/C mice showed the highest amounts of radioactivity (%ID/g) presented in the kidneys (31%) followed by the small intestine (10%) and stomach (9%); the lowest uptake was seen in the brain (0.5%). The incorporation of [68Ga]Ga‐PSMA‐617 into ME was successfully demonstrated and resulted in a stable nontoxic formulation as evaluated by in vitro and in vivo means

The aim of the study was to retrospectively evaluate the recurrence detection rate of Gallium-68-prostate-specific membrane antigen [(68Ga)PSMA] imaging and therapy (IT by contrast, bicalutamide and MAB were not found as significant factors. In the present study, (68Ga)PSMA I&T was found to be quite successful in determining lesions in the biochemical recurrence, which is consistent with the findings of other I&T studies and studies conducted with different PSMA ligands. Thus, it can be considered that the use of (68Ga)PSMA I&T will become increasingly common.

Purpose To evaluate the use of Ga-68-PSMA PET/CT for monitoring response to Lu-177-617 PSMA radioligand therapy in patients with metastatic castrate-resistant prostate cancer (mCRPC).Methods Patients from the University Hospital Bonn and the University Hospital Aachen were retrospectively reviewed for this study. We included 48 patients with mCRPC who were treated with Lu-177-PSMA-617 and whose records included Ga-68-PSMA PET/CT imaging before the first and after the third or fourth treatment cycle. A treatment response based on Ga-68-PSMA PET/CT was defined according to a modified version of the PERCIST criteria. A decline in PSA level of >= 50% was considered the reference standard. The sensitivity, specificity, positive and negative predictive values, and ROC curves were calculated, and patient survival times in relation to the PET results were also analysed.Results Ga-68-PSMA PET/CT had a sensitivity of about 85% and a specificity of between 55% and 65%. The negative and positive predictive values ranged between 70% and 78%. The fitted ROC area was 0.70. The survival time was about 19.6 months in patients with a treatment response, while nonresponders had a survival time of about 15.9 months. However, this difference between the groups was not statistically significant.Conclusion Our results indicate that Ga-68-PSMA PET/CT could be a useful tool for the evaluation of response to Lu-177-PSMA-617 radioligand therapy within a theranostic framework.

Thyroid incidentaloma is defined as a thyroid lesion incidentally and newly detected by imaging techniques performed for an unrelated purpose and especially for a non-thyroid disease. The aim of this review is to evaluate the prevalence and clinical significance of focal incidental radiolabelled prostate-specific membrane antigen (PSMA) uptake in the thyroid gland [PSMA thyroid incidentaloma (PTI)] revealed by PET/CT or PET/MRI. A comprehensive literature search of the PubMed/MEDLINE, Scopus, and Embase databases was conducted to find relevant published articles about the prevalence and clinical significance of PTIs detected by PET/CT or PET/MRI in patients studied for other oncologic purposes. Twelve articles were included in the systematic review. Among 23 PTIs, 6 were malignant (5 primary thyroid tumors and one metastasis from renal cell carcinoma), one was a follicular lesion of undetermined significance, and the rest were benign. Despite being very rare, though probably underestimated, PTIs frequently signal the presence of unexpected lesions in the thyroid which differ from the indicated reason for which the patient was initially scanned and concerning which the risk of malignancy is not negligible.

A limitation of using 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) for detection and staging of prostate cancer is a frequently observed halo artifact around the urinary bladder caused by inaccurate scatter correction (SC) of PET data. The aim of this study was to investigate the impact of unrenormalized absolute SC on 68Ga-PSMA PET quantification in PET/MRI of the prostate in 100 patients. Methods: The PET data of 100 patients were reconstructed twice using standard SC and improved unrenormalized SC. The visual presence of the halo artifact was rated in each PET data reconstruction using 5 grades (0, no halo artifact; 4, severe halo artifact). The number of visible lesions in the pelvis was recorded. SUVmean and SUVmax were measured in the lesions, in the bladder, in the gluteus maximus, and within the halo margin. Furthermore, the signal-to-noise-ratio and image noise were measured in all PET data. Relative differences between standard and unrenormalized SC were calculated. Results: With standard SC, the average grade in the presence of the halo artifact was 2 (moderate halo artifact), whereas for unrenormalized SC, the average grade was 0.9 (slight halo artifact). The same number of congruent lesions (n = 74) was detected for both PET data reconstructions. Relative changes in PET signal-to-noise-ratio and image noise were not statistically significant (P > 0.05). The mean (±SD) increase in SUVmean using unrenormalized SC was 23.0% ± 9.2% in the gluteus maximus, 7.1% ± 4.5% in the bladder, 325.4% ± 748.5% in the halo margin, and 12.4% ± 16.8% in all 74 detected lesions. The mean increase using unrenormalized SC in SUVmean was 17.5% for lesions inside the halo margin (38 lesions) and 6.9% for lesions outside the halo margin (36 lesions). Conclusion: For PET/MRI of prostate cancer using 68Ga-PSMA, a proper SC is important to ensure the best possible diagnostic quality and PET quantification. Unrenormalized absolute SC significantly reduces the halo artifact around the bladder and improves PET/MRI of the prostate.

Prostate specific membrane antigen (PSMA) is a promising target for the diagnosis and therapy of prostate cancer. In this report, a NOTA-conjugated precursor, NOTA-PSMA (also named PSMA-BCH), was synthesized by peptide synthesizer with the chemical purity over 95%. 68Ga-PSMA-BCH was obtained by radiolabeling NOTA-PSMA with 68GaCl3 with >99% radiochemical purity and 59–74 GBq/μmol specific activity. In vitro and in vivo study of 68Ga-PSMA-BCH showed high stability, high uptake in PSMA-expressing cells and tumor, fast clearance and low non-target uptake. 22Rv1 tumors were clearly observed in micro-PET images of and showed good retention. Compared with 68Ga-PSMA-617, 68Ga-PSMA-BCH showed comparable tumor uptake and tumor-background ratios. Indicating 68Ga-PSMA-BCH is a promising candidate for prostate cancer imaging and worthy of further clinical investigations.

Objective 68Ga-PSMA-uptake shows accumulation in the malignant lesions of prostate cancer patients as early as 5 min p.i. Studies indicate the value of adding an early image of the pelvis to the imaging protocol of 68Ga-PSMA-11 PET/CT scan showed contradictory results. In this study we planned to assess the significance of an additional early imaging in 68Ga-PSMA I&T PET/CT imaging in prostate cancer patients. Materials and methods A total of 35 prostate cancer patients referred to 68Ga-PSMA-I&T PET/CT imaging for restaging of the disease due to suspicion of relapse of the after definitive therapy were enrolled. First an early static pelvis image was obtained at a maximum of 300 s following injection of the radiotracer. Sixty minutes post injection a whole-body PET/CT scan was conducted with an emission time of 3 min per bed position. The lesions which were categorized as local recurrence, bone lesion and lymph node metastasis in the early images, were compared with the late images in terms of number of lesions detected and SUVmax values. Results 68Ga-PSMA-I&T PET/CT was positive in 23 of 35 patients (65.7%). A pathological uptake was observed in the prostatic bed site, in the pelvic lymph nodes, and in the bones in 17 patients (48.5%), 12 patients (34.2%), and 13 patients (37.1%), respectively. In one patient, focal pathological increased uptake in the prostatic bed with a SUVmax value of 5.8 was detected but this lesion disappeared in the late images (Fig. 1). The average SUVmax values of the lesions in the prostatic bed were 13.7 ± 12.1 versus 26.3 ± 23.8 in the 5 min and 60 min studies respectively (p Conclusion Our study is the first in the literature to evaluate the impact of adding an early static pelvic image to the 68GaPSMA-I&T scan, in the detection rate of the lesions. Although there was no marked discordance between the two sets of images, the addition of an early image to the imaging protocol of 68GaPSMA-I&T scan would increase the efficacy of detection of malignant lesions in the pelvis, which might show rapid clearance and has the risk of being masked by the urinary system activity.

68 Ga-PSMA-PET has an increasing importance in the evaluation of prostate cancer patients due to its high sensitivity and specificity in identifying neoplastic lesions in the clinical setting of elevated prostate-specific antigen (PSA). The objective of this study was to calculate the whole-body tumor burden using volumetric quantification of lesions detected in 68Ga-PSMA-PET of prostate cancer patients with biochemical recurrence and correlate these findings with clinical and image parameters. Each patient had their 68Ga-PSMA-PET analyzed for the presence of neoplastic lesions. Their PSA levels and clinical information were recorded. In positive cases, the tumor burden (TL-PSMA) was calculated with a semi-automatic software and manually, and the results are analyzed and tested. We analyzed 100 prostate cancer patients, mean age of 69.9 ± 9.7 years and a median PSA of 1.73 ng/dL. 68Ga-PSMA-PET identified neoplastic lesions in 72% of them. The median TL-PSMA was 55.95 ml (1.1–28,080 ml). TL-PSMA and PSA were strongly correlated (rho = 0.71, p

Purpose To determine the patterns of progression after 68Ga prostate-specific membrane antigen (PSMA)-ligand positron emission tomography (PET)/computed tomography (CT)-guided radiation therapy (RT) for recurrent oligometastatic prostate cancer (PCa). Methods and Materials One hundred and eight patients with increased prostate-specific antigen levels, who received 68Ga-PSMA-ligand PET/CT-guided RT for recurrent oligometastatic disease after primary therapy for PCa were included. The biochemical progression-free survival and distant disease-free survival after PSMA-ligand PET/CT-guided RT were determined. The patterns of progression were determined using renewed 68Ga-PSMA-ligand PET/CT in patients with biochemical progression and compared with the clinical target volume of the 68Ga-PSMA-ligand PET/CT-guided RT. The frequency of infield and outfield relapses was recorded. Results A total of 97.2% (105 of 108) of patients showed a decrease in prostate-specific antigen levels after RT and were classified as biochemical responders. After the median follow-up of 18 months, 43.5% (47 of 108) of the patients experienced biochemical progression, resulting in an estimated biochemical progression-free survival of 16 months. Renewed 68Ga-PSMA-ligand PET/CT allowed localization of recurrent disease in 91.7% (33 of 36) of patients. Analysis of the patterns of progression resulted in a cumulative infield relapse rate of 12.1% (4 of 33) and a cumulative outfield relapse rate of 87.9% (29 of 33). The resultant median disease-free survival was 11 months. In terms of the pattern of progression, we observed a shift in the pattern of metastases toward skeletal involvement and distant lymph node metastases. Of these patients, 45.5% (15 of 33) were treated with further RT to delay initiation or escalation of systemic therapies. Conclusion PSMA-ligand PET/CT-guided RT for relapsed PCa with limited tumor burden allowed individualization of treatment approaches, provided effective local control, and resulted in considerably prolonged biochemical progression-free survival. As indicated by the PSMA-ligand PET/CT-based patterns of progression, repeated PET/CT-guided RT may represent a treatment option in well-selected patients with relapse after RT for oligometastatic disease.

Prostate-specific membrane antigen (PSMA) is expressed on the endothelial cells of tumor-associated neovasculature of various nonprostatic benign and malignant neoplasms. Positive intense uptake on PET/CT imaging with 68Ga-labeled PSMA is noted in a patient with sinonasal glomangiopericytoma, and the same is noted to be absent following complete surgical excision. 68Ga-PSMA PET/CT may be a useful tool for early recurrence identification, differentiating recurrence from surgical site reparative tissues, and peptide receptor radionuclide therapy of residual lesions.

Purpose To evaluate the outcomes of metastasis-directed treatment (MDT) using stereotactic body radiotherapy (SBRT) for bone-only oligometastasis (OM) detected with gallium prostate-specific membrane antigen (68Ga-PSMA) PET/CT in castration-sensitive prostate cancer (PC) patients. Methods In this multi-institutional study, clinical data of 74 PC patients with 153 bone lesions who were undergoing MDT were retrospectively evaluated. Twenty-seven patients (36.5%) had synchronous, and 47 (63.5%) had metachronous OM. All patients had PC with 5 metastases or fewer detected by 68Ga-PSMA PET/CT and treated using SBRT with a median dose of 20 Gy. The prognostic factors for PC-specific survival (PCSS) and progression-free survival (PFS) were analyzed. Results The median follow-up was 27.3 months. Patients with synchronous OM were older and received higher rates of androgen deprivation therapy after SBRT compared with patients with metachronous OM. The 2-year PCSS and PFS rates were 92.0% and 72.0%, respectively. A prostate-specific antigen (PSA) decline was observed in 56 patients (75.7%), and 48 (64.9%) had a PSA response defined as at least 25% decrease of PSA after MDT. The 2-year local control rate per lesion was 95.4%. In multivariate analysis, single OM and PSA response after MDT were significant predictors for better PCSS and PFS. In-field recurrence was observed in 4 patients (6.5%) with 10 lesions at a median of 13.1 months after MDT completion. No serious late toxicity was observed. Conclusions We demonstrated that SBRT is an efficient and well-tolerated treatment option for PC patients with 5 bone-only oligometastases or fewer detected with 68Ga-PSMA PET/CT.

Optimization of injected gallium-68 (68Ga) activity for 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) studies is relevant for image quality, radiation protection, and from an economic point of view. However, no clear guidelines are available for 68Ga-PSMA studies. Therefore, a phantom study is performed to determine the highest coefficient of variation (COV) acceptable for reliable image interpretation and quantification.To evaluate image interpretation, the relationship of COV and contrast-to-noise ratio (CNR) was studied. The CNR should remain larger than five, according to the Rose criterion. To evaluate image quantification, the effect of COV on the percentage difference (PD) between quantification results of two studies was analyzed. Comparison was done by calculating the PD of the SUVmax. The maximum allowable PDSUVmax was set at 20%. The highest COV at which both criteria are still met is defined as COVmax. Of the NEMA Image Quality phantom, a 20 min/bed (2 bed positions) scan was acquired in list-mode PET (Philips Gemini TF PET/CT). The spheres to background activity ratio was approximately 9:1. To obtain images with different COV, lower activity was mimicked by reconstructions with acquisition times of 10 min/bed to 5 s/bed. Pairs of images were obtained by reconstruction of two non-overlapping parts of list-mode data.For the 10-mm diameter sphere, a COV of 25% still meets the criteria of CNRSUVmean ≥ 5 and PDSUVmax ≤ 20%. This phantom scan was acquired with an acquisition time of 116 s and a background activity concentration of 0.71 MBq/kg. Translation to a clinical protocol results in a clinical activity regimen of 3.5 MBq/kg min at injection. To verify this activity regimen, 15 patients (6 MBq/kg min) with a total of 22 lesions are included. Additional reconstructions were made to mimic the proposed activity regimen. Based on the CNRSUVmax, no lesions were missed with this proposed activity regimen.For our institution, a clinical activity regimen of 3.5 MBq/kg min at injection is acceptable, which indicates that activity can be reduced by almost 50% compared with the current code of practice. Our proposed method could be used to obtain an objective activity regimen for other PET/CT systems and tracers.