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Purpose: Radiolabeled PSMA-ligands play a major role in today's nuclear medicine. Since approval of [ 177 Lu]Lu-PSMA-617 for therapy of metastatic prostate cancer, availability of 177 Lu became bottleneck of supply due to the high demand. Recently, a theranostic PSMA-ligand, PSMA-GCK01, was developed which can be labeled either diagnostically with 99m Tc or therapeutically with 188 Re with both nuclides available from well-known generator systems. This novel tracer might aid to overcome aforementioned supply limitations. In this investigation, the biodistribution and general imaging characteristics of [ 99m Tc]Tc-PSMA-GCK01 were compared with the diagnostic reference compound [ 99m Tc]Tc-EDDA/HYNIC-iPSMA in patients with advanced stage prostate cancer. In addition, the binding of both ligands to PSMA was analyzed at the molecular level using molecular docking., Procedures: Two cohorts (n = 19 vs. n = 21) of patients with metastatic castration-resistant prostate cancer matched for age, tumor stage, and Gleason score underwent a planar gamma camera imaging with [ 99m Tc]Tc-EDDA/HYNIC-iPSMA or [ 99m Tc]Tc-PSMA-GCK01 prior to PSMA-ligand therapy for PSMA-phenotyping. The imaging data were retrospective analyzed for salivary gland, kidney, liver, soft tissue, and tumor uptake on a semi-automated ROI-analysis using HERMES Medical Solutions AB (HMS, Sweden)., Results: The data sets were semi-automated quantified on a ROI-based analysis. The tumor-to-background presented equal results of [ 99m Tc]Tc-PSMA-GCK01 compared to [ 99m Tc]Tc-EDDA/HYNIC-iPSMA. The physiological PSMA-positive organs like salivary gland presented also equal uptake in counts/MBq (salivary gland median 9.48 [ 99m Tc]Tc-PSMA-GCK01 vs. median 9.11 [ 99m Tc]Tc-EDDA/HYNIC-iPSMA), while liver-to-kidney ratio presented a slight shift to the liver parenchyma using [ 99m Tc]Tc-PSMA-GCK01 (0.83) compared to [ 99m Tc]Tc-EDDA/HYNIC-iPSMA (0.55) with no statistical significance. This is in agreement with the results from the docking study revealing only a minor difference in the docking scores for both ligands., Conclusions: The novel theranostic tracer [ 99m Tc]Tc/[ 188 Re]Re-PSMA-GCK01 demonstrates comparable general imaging characteristic with the reference compound [ 99m Tc]Tc-EDDA/HYNIC-iPSMA. These results pave the way for the PSMA-targeting imaging and theranostic agents for a broader, rather low-cost, generator applied radio-ligand therapy utilization., (© 2023. The Author(s).)

Background: In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications., Objective: We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa., Design, Setting, and Participants: The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting., Outcome Measurements and Statistical Analysis: Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores., Results and Limitations: After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [ 177 Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [ 223 Ra]RaCl 2 remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both [ 18F ]FDG and PSMA PET prior to [ 177 Lu]Lu-PSMA therapy., Conclusions: There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community., Patient Summary: There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Metastatic prostate carcinoma overexpresses prostate-specific membrane antigen (PSMA), making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience with a series of 73 castration-resistant prostate carcinoma patients treated with 225 Ac-PSMA-617, identifying variables predictive for overall survival (OS) and progression-free survival (PFS) after 225 Ac-PSMA-617 treatment. Methods: 225 Ac-PSMA-617 was administered to patients who had metastatic castration-resistant prostate carcinoma and who had exhausted available therapy options for their disease. Full blood count, glomerular filtration rate, and liver function test were obtained at baseline and on follow-up for evaluation of toxicity. 68 Ga-PSMA PET/CT was obtained at baseline, before every treatment cycle, and on follow-up for selection of patients for treatment, to determine the activity of the treatment agent to be administered, and for response assessment. Serial prostate-specific antigen (PSA) was obtained for PSA response assessment. Results: Seventy-three men (mean age, 69 y; range, 45-85 y) with metastatic castration-resistant prostate carcinoma were treated with 210 cycles of 225 Ac-PSMA-617. In 70% of patients, a PSA decline of greater than or equal to 50% was obtained; 82% of patients had any PSA decline. In 29% of patients, all lesions on 68 Ga-PSMA PET resolved in response to treatment. During follow-up, 23 patients experienced disease progression, whereas 13 patients died from their disease. The estimated median PFS and OS were 15.2 mo (95% CI, 13.1-17.4) and 18 mo (95% CI, 16.2-19.9), respectively. In univariate analyses, factors such as baseline PSA, any PSA decline, PSA decline of greater than or equal to 50%, prior chemotherapy, prior radiation therapy, and baseline hemoglobin level were associated with longer PFS and OS (all P s < 0.05). In multivariate analyses, there was a negative association between prior 177 Lu-PSMA therapy and PFS, and a positive association between PSA decline of greater or equal to 50% and PFS. Only a PSA decline of greater than or equal to 50% remained significantly associated with OS on multivariate analyses. Xerostomia was seen in 85% of patients but was not severe enough to warrant discontinuing treatment. Anemia was seen in 27 patients; no patients had grade IV bone marrow toxicity. Renal failure of grade III or IV was seen in 5 patients with baseline renal impairment. Conclusion: In this study, a PSA decline of greater than or equal to 50% after treatment with 225 Ac-PSMA-617 was proven by multivariate analyses to be significantly associated with OS and PFS. Furthermore, previous 177 Lu-PSMA treatment was negatively associated with PFS in both univariate and multivariate analyses., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

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 [ 68 Ga]Ga 3+ -radiolabelling and positron emission tomography/computed tomography (PET) imaging of PSMA expression in vivo. We herein report the formulation of [ 68 Ga]Ga-PSMA-617 into a ME ≤40 nm including its evaluation for improved cellular toxicity and in vivo biodistribution. The [ 68 Ga]Ga-PSMA-617-ME was tested in vitro for its cytotoxicity to HEK293 and PC3 cells. [ 68 Ga]Ga-PSMA-617-ME was administered intravenously in BALB/c mice followed by microPET/computed tomography (CT) imaging and ex vivo biodistribution determination. [ 68 Ga]Ga-PSMA-617-ME indicated negligible cellular toxicity at different concentrations. A statistically higher tolerance towards the [ 68 Ga]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 [ 68 Ga]Ga-PSMA-617 into ME was successfully demonstrated and resulted in a stable nontoxic formulation as evaluated by in vitro and in vivo means., (© 2019 John Wiley & Sons, Ltd.)

The introduction of 18 F-labeled prostate-specific membrane antigen (PSMA)-targeted PET/CT tracers, first 18 F-DCFPyL (2-(3-{1-carboxy-5-[(6- 18 F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) and more recently 18 F-PSMA-1007 (((3 S, 10 S, 14 S )-1-(4-((( S )-4-carboxy-2-(( S )-4-carboxy-2-(6- 18 F-fluoronicotinamido)butanamido)butanamido)methyl)phenyl)-3-(naphthalen-2-ylmethyl)-1,4,12-trioxo-2,5,11,13-tetraazahexadecane-10,14,16-tricarboxylic acid)), have demonstrated promising results for the diagnostic workup of prostate cancer. This clinical study presents an intraindividual comparison to evaluate tracer-specific characteristics of 18 F-DCFPyL versus 18 F-PSMA-1007. Methods: Twelve prostate cancer patients, drug-naïve or before surgery, received similar activities of about 250 MBq of 18 F-DCFPyL and 18 F-PSMA-1007 48 h apart and were imaged 2 h after injection on the same PET/CT scanner using the same reconstruction algorithm. Normal-organ biodistribution and tumor uptake were quantified using SUV max Results: PSMA-positive lesions were detected in 12 of 12 prostate cancer patients. Both tracers, 18 F-DCFPyL and 18 F-PSMA-1007, detected the same lesions. No statistical significance could be observed when comparing the SUV max of 18 F-DCFPyL and 18 F-PSMA-1007 for local tumor, lymph node metastases, and bone metastases. With regard to normal organs, 18 F-DCFPyL had statistically significant higher uptake in kidneys, urinary bladder, and lacrimal gland. Vice versa, significantly higher uptake of 18 F-PSMA-1007 in muscle, submandibular and sublingual gland, spleen, pancreas, liver, and gallbladder was observed. Conclusion: Excellent imaging quality was achieved with both 18 F-DCFPyL and 18 F-PSMA-1007, resulting in identical clinical findings for the evaluated routine situations. Nonurinary excretion of 18 F-PSMA-1007 might present some advantage with regard to delineation of local recurrence or pelvic lymph node metastasis in selected patients; the lower hepatic background might favor 18 F-DCFPyL in late stages, when rare cases of liver metastases can occur., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: To compare the diagnostic accuracy of Ga-prostate-specific membrane antigen (PSMA)-HBED-CC PET/computed tomography (CT) imaging for the detection of androgen-dependent recurrent prostate carcinoma (ADPC) in Black South Africans (BSAs) versus White South Africans (WSAs) with increasing serum prostate-specific antigen (PSA) values below or equal to 10 ng/ml., Patients and Methods: A total of 61 patients with ADPC were prospectively included in the study (mean age: 66.7 years): 38 WSAs and 23 BSAs. Ga-PSMA-HBED-CC PET/CT imaging results obtained were related to serum PSA levels and to ethnicity., Results: A total of 41 (67%) patients had a positive Ga-PSMA-HBED-CC scan result. Ga-PSMA-HBED-CC PET/CT positivity was significantly higher in patients with PSA values more than 2 ng/ml [32/38 (84%) patients] when compared with patients with PSA values less than 0.5 ng/ml [6/11 (55%) patients] or PSA values of 0.5-2 ng/ml [3/12 (25%) patients] (P=0.0001). Mean PSA values proved not significantly different in patients presenting with extrapelvic involvement when compared with those with intrapelvic involvement or between patients who presented with bone involvement versus those who did not on Ga-PSMA-HBED-CC PET/CT) (P≥0.147). Age, Gleason-scores, median PSA values, the frequency of a positive scan result, the frequency of bone involvement, and extrapelvic involvement proved similar in WSAs and BSAs (P≥0.417)., Conclusion: Ga-PSMA-HBED-CC PET/CT imaging identified a recurrence in 67% of the patients under study. Higher PSA levels were associated with Ga-PSMA-HBED-CC PET/CT positivity and the detection rate. Imaging results obtained proved similar in BSAs and WSAs, suggesting that the tumor burden and growth rate of ADPC are similar in both races.

We report a case of a 65-year-old man with prostate cancer; his treatment history included radical prostatectomy followed by radiation therapy and subsequent androgen deprivation therapy for more than 5 years. He currently presented with a history of rising prostate-specific antigen and complained of jaw aches. Ga-prostate-specific membrane antigen PET/CT study performed for suspected biochemical recurrence demonstrated vertebral lesions and lesion in his jaw. Subsequent biopsy of jaw lesion demonstrated prostate cancer metastases.

Purpose: The incidence of prostate cancer is 60% higher and the mortality rate is two- to three-times greater in black versus white men. We report on differences in 68 Ga-PSMA-11 PET/CT imaging findings in 77 black South-African (BSAs) and 18 white South-African (WSAs) treatment-naïve primary prostate carcinoma (PPC) patients., Methods: 68 Ga-PSMA-11 PET/CT imaging findings were compared to histological, biochemical and morphological imaging data. Patients were grouped into three Gleason grade groups (GG), GG 1 (scores 3 + 3 and 3 + 4), GG2 (scores 4 + 3 and 4 + 4) and GG3 (scores 9 and 10), and the PSA difference among the groups was determined. Inter-racial difference in SUVmax of the primary tumor as well as its correlation with serum PSA were also determined., Results: Ninety-three out of 95 PPC where readily identified on 68 Ga-PSMA-11 PET/CT imaging. Median PPC SUVmax and serum PSA values proved significantly higher (p = 0.033 and p = 0.003) in GG3 patients (median 16.4 and 180 ng/ml) when compared to GG1 patients (median 9.6 and 25.1 ng/ml) or GG2 patients (median 8.8 and 46.2 ng/ml). SUVmax significantly correlated with serum PSA-values (r = 0.377 (p = 0.0001)). Age, frequency of lymph node involvement and distant metastases, and GGs (p ≥ 0.153) were similar in BSAs and WSAs, both median serum PSA-values as well as SUVmax values proved significantly higher in BSAs when compared to WSAs, respectively, 81.6 ng/ml versus 14.5 ng/ml (p = 0.0001) and 11.9 versus 4.38 (p = 0.004). Moreover, Gleason-score normalized median SUVmax values proved 2.5 times higher in BSAs when compared to WSAs (p = 0.005)., Conclusion: SUVmax values proved significantly related to GG and to be significantly higher in BSAs when compared to WSAs. Also, SUVmax significantly correlated with serum PSA values, which was significantly higher in BSAs when compared with WSAs.

The objective of this study was to assess the impact of 68 Ga-prostate-specific membrane antigen ( 68 Ga-PSMA) PET/CT on the management of prostate cancer in patients with biochemical recurrence (BCR). Methods: Documented management plans before and after 68 Ga-PSMA PET/CT in 100 patients with BCR were retrospectively reviewed, and changes in plans were recorded. Results: Management changed after 68 Ga-PSMA PET/CT in 39 patients (39%). The management changes occurred in 23 (33.8%) of 68 patients with radical prostatectomy and 16 (50%) of 32 patients previously treated with radical radiotherapy. Positive scan results ( P < 0.001) and higher prostate-specific antigen (PSA) levels ( P = 0.024) were associated with management changes. No significant association with management change was found for Gleason grade, stage, presence of metastatic disease, PSA velocity, or PSA doubling time. Conclusion: 68 Ga-PSMA PET/CT altered management in 39% of patients with BCR, and changes occurred more often in patients with radical radiotherapy treatment, positive 68 Ga-PSMA scan results, and higher PSA levels., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

We describe the finding of a metastatic superscan detected by Ga-PSMA PET/CT imaging. A 63-year-old man with metastatic prostate carcinoma underwent Ga-PSMA PET/CT imaging for staging and evaluation of the most appropriate therapeutic option. Images demonstrated diffuse and extensive skeletal uptake in the axial and appendicular skeleton, corresponding to the typical red marrow distribution. Intense soft tissue uptake was also seen in the prostate and multiple pelvic and abdominal lymph nodes.

Prostate-specific membrane antigen (PSMA), a type II glycoprotein, is highly expressed in almost all prostate cancers. By playing such a universal role in the disease, PSMA provides a target for diagnostic imaging of prostate cancer using positron emission tomography/computed tomography (PET/CT). The PSMA-targeting ligand Glu-NH-CO-NH-Lys-(Ahx)-HBED-CC (DKFZ-PSMA-11) has superior imaging properties and allows for highly-specific complexation of the generator-based radioisotope Gallium-68 ((68)Ga). However, only module-based radiolabeling procedures are currently available. This study intended to develop a single vial kit solution to radiolabel buffered DKFZ-PSMA-11 with (68)Ga. A (68)Ge/(68)Ga-generator was utilized to yield (68)GaCl3 and major aspects of the kit development were assessed, such as radiolabeling performance, quality assurance, and stability. The final product was injected into patients with prostate cancer for PET/CT imaging and the kit performance was evaluated on the basis of the expected biodistribution, lesion detection, and dose optimization. Kits containing 5 nmol DKFZ-PSMA-11 showed rapid, quantitative (68)Ga-complexation and all quality measurements met the release criteria for human application. The increased precursor content did not compromise the ability of (68)Ga-DKFZ-PSMA-11 PET/CT to detect primary prostate cancer and its advanced lymphatic- and metastatic lesions. The (68)Ga-DKFZ-PSMA-11 kit is a robust, ready-to-use diagnostic agent in prostate cancer with high diagnostic performance.