Purpose The first aim of this study was to evaluate 68 Ga-PSMA HBED-CC conjugate 11 positron emission tomography (PSMA PET) parameters for assessment of response to 177 Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC). The second aim was to investigate factors associated with overall survival (OS). Methods We retrospectively assessed mean standardized uptake values (SUVmean) and total tumor volumes (TTV) on PSMA PET in 38 of 55 mCRPC patients before and after RLT. PSA testing and PSMA PET/CT(MRI) imaging were performed during the 8 weeks before and the 6 weeks after RLT. PSMA PET and CT(MRI) images were reviewed separately according to the modified PET Response Criteria in Solid Tumors (mPERCIST) and RECIST1.1. The results were compared with PSA responses. Associations between OS and the RECIST evaluation and changes in SUVmean, TTV, and PSA, CRP, LDH, hemoglobin and ALP levels were determined in a univariable survival analysis. Results The median PSA level at the time of pretherapy PSMA PET/CT(MRI) was 60.8 ng/ml (IQR 15.4, 264.2 ng/ml). After RLT the median PSA level decreased by 44%, TTV by 45.1%, SUVmean by 25.8% and RECIST by 11.3%. A PSA response was seen in 18 patients (47.4%), stable disease in 12 (31.6%) and progressive disease in 8 (21.1%). Contrary to the changes in SUVmean and the RECIST evaluation, the change in TTV was significantly associated with PSA response ( p = 0.15, p = 0.58, and p < 0.001, respectively). After a median follow-up of 17 months (IQR 8.0, 24.2 months), 11 patients (28.9%) had died of their prostate cancer. The changes in both TTV and PSA levels were associated with OS (HR 1.001, 95% CI 1–1.003, p = 0.04, and HR 1.004, 95% CI 1.001–1.008, p = 0.01, respectively), while the changes in SUVmean and the RECIST evaluation were not. The pre-therapy CRP level was also associated with OS (HR 1.07, 95% CI 1.009–1.14, p = 0.02). Conclusion TTV on PSMA PET seems to be a reliable parameter for response assessment in mCRPC patients undergoing RLT and might overcome the limitations of RECIST in prostate cancer. Furthermore, the change in TTV was significantly associated with OS in our cohort.

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Primary staging of prostate cancer relies on modalities, which are limited. We evaluate simultaneous [Ga]Ga-PSMA-11 PET (PSMA-PET)/MRI as a new diagnostic method for primary tumor-node-metastasis staging compared with histology and its impact on therapeutic decisions. We investigated 122 patients with PSMA-PET/MRI prior to planned radical prostatectomy (RP). Primary endpoint was the accuracy of PSMA-PET/MRI in tumor staging as compared with staging-relevant histology. In addition, a multidisciplinary team reassessed the initial therapeutic approach to evaluate its impact on the therapeutic management. PSMA-PET/MRI correctly identified prostate cancer in 119 of 122 patients (97.5%). Eighty-one patients were treated with RP and pelvic lymphadenectomy. The accuracy for T staging was 82.5% [95% confidence interval (CI), 73-90; < 0.001], for T2 stage was 85% (95% CI, 71-94; < 0.001), for T3a stage was 79% (95% CI, 43-85; < 0.001), for T3b stage was 94% (95% CI, 73-100; < 0.001), and for N1 stage was 93% (95% CI, 84-98; < 0.001). PSMA-PET/MRI changed the therapeutic strategy in 28.7% of the patients with either the onset of systemic therapy/radiotherapy ( = 16) or active surveillance ( = 19). PSMA-PET/MRI can provide an accurate staging of newly diagnosed prostate cancer. In addition, treatment strategies were changed in almost a third of the patients due to the information of this hybrid imaging technique.

Background To assess which parameters of [68Ga]Ga‐PSMA‐11 positron emission tomography (PSMA‐PET) predict response to systemic therapies in metastatic (m) castration‐resistant prostate cancer (CRPC). In addition, to investigate which of these factors are associated with overall survival (OS). Methods We retrospectively assessed the following PSMA‐PET parameters in 43 patients before and after systemic therapies for mCRPC: PSMA total tumor volume (TTV), mean standardized uptake value (SUVmean), SUVmax, and SUVpeak. prostate‐specific antigen (PSA) levels and PSMA‐PET/CT(magnetic resonance imaging [MRI]) imaging were both performed within 8 weeks before and 6 weeks after systemic therapy. PSMA‐PET and CT (MRI) images were reviewed according to the modified PET Response Criteria in Solid Tumors (PERCIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results were compared to PSA response. Univariable survival analyses were performed. Results Overall, 43 patients undergoing 67 systemic therapies were included (9 patients radium‐223, 12 cabazitaxel, 22 docetaxel, 6 abiraterone, and 18 enzalutamide). Median serum PSA level before any therapy was 11.3 ng/mL (interquartile range [IQR] = 3.3, 30.1). Delta (d) PSA after systemic therapies was −41%, dTTV 10.5%, dSUVmean −7.5%, dSUVmax −13.3%, dSUVpeak −12%, and dRECIST −13.3%. Overall, 31 patients had dPSA response (46.3%), 12 stable disease (17.9%), and 24 progressive disease (35.8%). All observed PET parameters, as well as the RECIST evaluation, were significantly associated with PSA response (dTTV P = .003, dSUVmean P = .003, dSUVmax P = .011, dSUVpeak P < 0001, dRECIST P = .012), while RECIST assessment was applicable in 37 out of 67 patients (55.2%). Within a median follow‐up of 33 months (IQR = 26, 38), 10 patients (23.3%) died of PC. On univariable survival analyses, neither the investigated PET parameters nor PSA level or RECIST criteria were associated with OS. Conclusion PSMA‐PET provides reliable parameters for prediction of response to systemic therapies for mCRPC. These parameters, if confirmed, could enhance RECIST criteria, specifically concerning its limitations for sclerotic bone lesions.

ObjectiveTo evaluate the diagnostic performance of [68Ga]Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA-PET) in the early detection of metastases in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) for clinically non-metastatic prostate cancer, to compare it to CT/MRI alone and to assess its impact on further therapeutic decisions.Material and methodsWe retrospectively assessed 117 consecutive hormone-naïve BCR patients who had 68Ga-PSMA 11 PET/CT (n = 46) or PET/MRI (n = 71) between May 2014 and January 2017. BCR was defined as two PSA rises above 0.2 ng/ml. Two dedicated uro-oncological imaging experts (radiology/nuclear medicine) reviewed separately all images. All results were presented in a blinded sequential fashion to a multidisciplinary tumorboard in order to assess the influence of PSMA-PET imaging on decision-making.ResultsThe median time from RP to BCR was 36 months (IQR 16–72). Overall, 69 (59%) patients received postoperative radiotherapy. Median PSA level at the time of imaging was 1.04 ng/ml (IQR 0.58–1.87). PSMA-positive lesions were detected in 100 (85.5%) patients. Detection rates were 65% for a PSA value of 0.2 to <0.5 ng/ml, 85.7% for 0.5 to <1, 85.7% for 1 to <2 and 100% for ≥2. PSMA-positive lesions could be confirmed by either histology (16%), PSA decrease in metastasis-directed radiotherapy (45%) or additional information in diffusion-weighted imaging when PET/MRI was performed (18%) in 79% of patients. PSMA-PET detected lesions in 67 patients (57.3%) who had no suspicious correlates according to the RECIST 1.1 criteria on MRI or CT. PSMA-PET changed therapeutic decisions in 74.6% of these 67 patients (p < 0.001), with 86% of them being considered for metastases-directed therapies.ConclusionsWe confirm the high performance of PSMA-PET imaging for the detection of disease recurrence sites in patients with BCR after RP, even at relatively low PSA levels. Moreover, it adds significant information to standard CT/MRI, changing treatment strategies in a significant number of patients.

One of the most promising classes of iron chelators are α-N-heterocyclic thiosemicarbazones with Triapine as the most prominent representative. In several clinical trials Triapine showed anticancer activity against hematological diseases, however, studies on solid tumors failed due to widely unknown reasons. Some years ago, it was recognized that “terminal dimethylation” of thiosemicarbazones can lead to a more than 100-fold increased activity, probably due to interactions with cellular copper depots. To better understand the structural requirements for the switch to nanomolar cytotoxicity, we systematically synthesized all eight possible N-methylated derivatives of Triapine and investigated their potential against Triapine-sensitive as well as -resistant cell lines. While only the “completely” methylated compound exerted nanomolar activity, the data revealed that all compounds with at least one N-dimethylation were not affected by acquired Triapine resistance. In addition, these compounds were highly synergistic with copper treatment accompanied by induction of reactive oxygen species and massive necrotic cell death.

[Ga]Ga-Pentixafor positron emission tomography/magnetic resonance imaging may possibly be useful for CXCR4-based CLL imaging.

MALT lymphomas express the chemokine receptor CXCR4 on a regular basis, and [68Ga]Ga-Pentixafor-PET has been shown to quantify CXCR4 expression non-invasively. We, therefore, aimed to evaluate [68Ga]Ga-Pentixafor-PET/MRI for the non-invasive assessment of MALT lymphomas. Methods: We included 36 MALT lymphoma patients, who had not undergone previous systemic or radiation therapy, in our prospective, IRB-approved, proof-of-concept study. Involved anatomic regions were the orbit (n=14), stomach (n=10), lungs (n=5), and other sites (soft-tissues n=3; adrenal gland, tonsils, parotid gland, and urinary bladder n=1, respectively). MRI sequences included an axial 2-point Dixon T1 VIBE SPAIR 3D sequence for PET attenuation correction; a coronal T2 HASTE sequence; and an axial echo-planar imaging SPAIR-based diffusion-weighted sequence (DWI) obtained during free-breathing (b-values, 50 and 800), with corresponding ADC (apparent diffusion coefficient) maps. Results: In 33/36 patients, there were MALT lymphomas with an increased uptake of [68Ga]Ga-Pentixafor; all current lymphoma manifestations showed an increased uptake and, accordingly, were positive on the PET/MRI. The remaining three patients had undergone surgery for their orbital MALT lymphomas prior to PET/MRI. Mean SUVmax was 8.6 ± 4.7, mean SUVmean was 4.7 ± 1.8, and mean SUVpeak was 8.0 ± 4.2. The mean SUVmax of the liver was 1.8, and the mean tumor-to-liver ratio was 2.9 ± 2.0. There were no significant differences in SUVmax (P=0.22), SUVmean (P=0.53), SUVpeak (P=0.29), or SUVt/l (P=0.92) between the four anatomic regions (orbit, stomach, lungs, other). The mean tumor volume was 146 ± 499. Conclusions: Our results thus indicate that [68Ga]Ga-Pentixafor-PET is feasible for the assessment of MALT lymphomas, with a good tumor-to-background ratio in terms of radiotracer uptake.