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1.
Nucl Med Commun ; 45(7): 629-641, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38835183

ABSTRACT

OBJECTIVE: To investigate the relationship between intraprostatic 68Ga-prostate-specific membrane antigen (PSMA) uptake values and volumetric parameters derived from early pelvic and standard-time whole-body 68Ga-PSMA PET/computed tomography (CT) images in untreated prostate cancer (PCa) patients, and to assess the predictive significance of these data in relation to disease prognosis, comparing them with the Gleason score, clinical risk classification and the presence of metastatic disease detected in 68Ga-PSMA PET/CT imaging. METHODS: Eighty-one newly diagnosed PCa patients underwent early phase pelvic imaging at the 5th minute and standard time whole-body imaging at the 60th minute. Various threshold values were used in intraprostatic delineations to compute maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), intraprostatic PSMA tumor volume and intraprostatic total lesion PSMA uptake. Correlations between early and standard time measurements, as well as changes in SUV parameters over time, were examined. The association of these values with Gleason score, clinical risk status (National Comprehensive Cancer Network), and metastatic disease was explored. RESULTS: SUVmax measurements from both early and standard time images distinguished all three groups (clinical risk scores, Gleason score and metastatic group), with standard imaging demonstrating statistical superiority in receiver operating characteristic analyses. Strong correlations were observed between early and standard-time PET parameters. Changes in intraprostatic SUVmax and SUVmean values over time did not exhibit predictive value. CONCLUSION: Although intraprostatic PSMA PET parameters generally aligned at both early and standard times, parameters obtained from standard time images showed more robust correlations with clinical risk scores, Gleason score and metastasis status in newly diagnosed, untreated PCa patients.


Subject(s)
Edetic Acid , Gallium Isotopes , Gallium Radioisotopes , Oligopeptides , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Prostatic Neoplasms/metabolism , Aged , Middle Aged , Edetic Acid/analogs & derivatives , Tumor Burden , Time Factors , Aged, 80 and over
2.
Clin Nucl Med ; 49(7): e324-e326, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38689449

ABSTRACT

ABSTRACT: An 84-year-old man with prostate adenocarcinoma underwent 68 Ga-PSMA PET/CT due to PSA recurrence. Foci of 68 Ga-PSMA uptake were observed in bilateral adrenal glands. Adrenal MRI showed metastasis only in the left adrenal gland. Metastatic 68 Ga-PSMA uptake was also observed in the mediastinum and bone. Enzalutamide treatment was started. Follow-up 68 Ga-PSMA PET/CT scan showed regression in both adrenal gland metastases and other metastases.


Subject(s)
Adenocarcinoma , Adrenal Gland Neoplasms , Gallium Isotopes , Gallium Radioisotopes , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Aged, 80 and over , Adrenal Gland Neoplasms/diagnostic imaging , Adrenal Gland Neoplasms/secondary , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/secondary , Edetic Acid/analogs & derivatives , Oligopeptides
3.
Clin Nucl Med ; 49(7): e319-e320, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38689441

ABSTRACT

ABSTRACT: Finding of the prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer (PC) cells that have made it possible to evaluate the patients with PC with a single imaging method. 68 Ga-PSMA PET/CT is now part of the routine in patients with PC. After several years of clinical experience with PSMA tracers, the specificity is satisfactory; however, concerns about the specificity are raising day by day due to the newly laid out nonprostatic malignant and benign lesions with high PSMA expression. Herein, we present an incidental 68 Ga-PSMA uptake in an intramuscular granular cell tumor.


Subject(s)
Edetic Acid , Gallium Isotopes , Gallium Radioisotopes , Positron Emission Tomography Computed Tomography , Humans , Male , Edetic Acid/analogs & derivatives , Oligopeptides , Muscle Neoplasms/diagnostic imaging , Aged , Middle Aged
4.
Clin Nucl Med ; 49(7): e373-e374, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38693645

ABSTRACT

ABSTRACT: A 62-year-old man with de novo large volume metastatic prostate cancer to the bone, liver, and nodes status post multiple lines of therapy including external beam radiation to T12-L2 approximately 13 months prior underwent 68 Ga-PSMA PET/CT to determine eligibility for 177 Lu-PSMA therapy. 68 Ga-PSMA PET/CT demonstrated tracer-avid osseous and nodal lesions consistent with metastases. In addition, regional geographic tracer avidity was seen in the midline left hepatic lobe associated with capsular retraction and demonstrated no FDG avidity on subsequent imaging, probably inflammatory related to prior radiation to T12-L2.


Subject(s)
Inflammation , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Humans , Male , Middle Aged , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/pathology , Inflammation/diagnostic imaging , Liver/diagnostic imaging , Gallium Radioisotopes , Gallium Isotopes , Edetic Acid/analogs & derivatives , Oligopeptides , Glutamate Carboxypeptidase II/metabolism , Antigens, Surface
5.
Cancer Imaging ; 24(1): 57, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711135

ABSTRACT

BACKGROUND: PSMA PET/CT is a predictive and prognostic biomarker for determining response to [177Lu]Lu-PSMA-617 in patients with metastatic castration resistant prostate cancer (mCRPC). Thresholds defined to date may not be generalizable to newer image reconstruction algorithms. Bayesian penalized likelihood (BPL) reconstruction algorithm is a novel reconstruction algorithm that may improve contrast whilst preventing introduction of image noise. The aim of this study is to compare the quantitative parameters obtained using BPL and the Ordered Subset Expectation Maximization (OSEM) reconstruction algorithms. METHODS: Fifty consecutive patients with mCRPC who underwent [68Ga]Ga-PSMA-11 PET/CT using OSEM reconstruction to assess suitability for [177Lu]Lu-PSMA-617 therapy were selected. BPL algorithm was then used retrospectively to reconstruct the same PET raw data. Quantitative and volumetric measurements such as tumour standardised uptake value (SUV)max, SUVmean and Molecular Tumour Volume (MTV-PSMA) were calculated on both reconstruction methods. Results were compared (Bland-Altman, Pearson correlation coefficient) including subgroups with low and high-volume disease burdens (MTV-PSMA cut-off 40 mL). RESULTS: The SUVmax and SUVmean were higher, and MTV-PSMA was lower in the BPL reconstructed images compared to the OSEM group, with a mean difference of 8.4 (17.5%), 0.7 (8.2%) and - 21.5 mL (-3.4%), respectively. There was a strong correlation between the calculated SUVmax, SUVmean, and MTV-PSMA values in the OSEM and BPL reconstructed images (Pearson r values of 0.98, 0.99, and 1.0, respectively). No patients were reclassified from low to high volume disease or vice versa when switching from OSEM to BPL reconstruction. CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT quantitative and volumetric parameters produced by BPL and OSEM reconstruction methods are strongly correlated. Differences are proportional and small for SUVmean, which is used as a predictive biomarker. Our study suggests that both reconstruction methods are acceptable without clinical impact on quantitative or volumetric findings. For longitudinal comparison, committing to the same reconstruction method would be preferred to ensure consistency.


Subject(s)
Algorithms , Bayes Theorem , Gallium Isotopes , Gallium Radioisotopes , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms, Castration-Resistant , Humans , Male , Positron Emission Tomography Computed Tomography/methods , Prostatic Neoplasms, Castration-Resistant/diagnostic imaging , Prostatic Neoplasms, Castration-Resistant/pathology , Aged , Middle Aged , Retrospective Studies , Oligopeptides , Edetic Acid/analogs & derivatives , Whole Body Imaging/methods , Radiopharmaceuticals , Aged, 80 and over , Neoplasm Metastasis , Image Processing, Computer-Assisted/methods , Dipeptides/therapeutic use
6.
Nucl Med Rev Cent East Eur ; 27(0): 6-12, 2024.
Article in English | MEDLINE | ID: mdl-38680016

ABSTRACT

BACKGROUND: As in disease recurrence, providing clinicians with the exact extent of the disease at the time of initial diagnosis is key in the management and individual treatment of prostate cancer (PC) patients. Intending to examine the usefulness of gallium- 68 PSMA-11 positron emission tomography/computed tomography ([68Ga]Ga-PSMA-11 PET/CT) and to determine if there is a correlation between prostate-specific antigen (PSA) serum values, WHO/ISUP (World Health Organization/International Society of Urological Pathology's) grade group of the tumor and SUVmax (maximized standardized uptake value) values we retrospectively analyzed PET/CT studies performed for initial staging of the disease. PATIENTS AND METHODS: We retrospectively evaluated 34 studies of patients who underwent [68Ga]Ga-PSMA-11 PET/CT as part of the initial staging of prostate cancer. All patients had prostate cancer confirmed by histological assessment after biopsy and had Gleason score and PSA serum values obtained. The mean PSA value was 33.8 ± 40.9 nmol/L (range 2.2-232). RESULTS: Nineteen patients had extended disease (55.9%). The mean SUVmax in prostate lesions was 19.5 ± 12.6. The mean value of SUVmax of PET studies in the high-risk group was significantly higher than those of low risk (23.5 ± 13.2 and 10.6 ± 5.4, p < 0.05). A positive correlation was observed between the ISUP group and SUVmax value of prostate lesions (Pearson's r = 0.557, p < 0.01). A positive correlation was also found in the comparison between PSA values and SUVmax (Pearson's r = 0.34, p < 0.05). CONCLUSIONS: In our study, [68Ga]Ga-PSMA-11 PET/CT scans detected the extended disease in more than half of the patients. Locating disease beyond the prostate gland allowed better informed clinical decisions and modified treatment. A positive correlation was found between intraprostatic SUVmax values and the ISUP group of prostate cancer. High-risk patients had SUVmax values that were significantly higher than those of low-risk patients. The correlation between the Gleason score and SUVmax value can be explained by the increased intensity of PSMA expression as the tumor grade increases.


Subject(s)
Edetic Acid , Gallium Isotopes , Gallium Radioisotopes , Neoplasm Staging , Oligopeptides , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Edetic Acid/analogs & derivatives , Aged , Middle Aged , Retrospective Studies , Aged, 80 and over , Prostate-Specific Antigen/blood
7.
Clin Nucl Med ; 49(7): e346-e350, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38687004

ABSTRACT

ABSTRACT: Metastatic prostate cancer to the appendicular skeleton is rare. We present an 86-year-old man with undiagnosed prostate cancer presenting with unilateral foot pain. CT and MRI demonstrated a sclerotic midfoot suggestive of an infiltrative process. In view of an elevated PSA, metastatic disease was suspected, and bone scan confirmed osteoblastically active pelvic and lower-limb skeletal lesions. Subsequent prostate biopsy confirmed prostate adenocarcinoma. Staging 68 Ga-PSMA PET/CT demonstrated PSMA-avid intraprostatic malignancy with pelvic and right lower-limb skeletal metastases. This is an unusual case of de novo 68 Ga-PSMA-avid metastatic prostate cancer with atypical lower-limb skeletal metastases presenting with foot pain.


Subject(s)
Bone Neoplasms , Edetic Acid , Gallium Isotopes , Gallium Radioisotopes , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Aged, 80 and over , Bone Neoplasms/secondary , Bone Neoplasms/diagnostic imaging , Edetic Acid/analogs & derivatives , Oligopeptides , Lower Extremity/diagnostic imaging , Multimodal Imaging
8.
Clin Nucl Med ; 49(7): e340-e345, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38598534

ABSTRACT

ABSTRACT: We present a case series of 5 patients diagnosed with schwannoma and 1 patient diagnosed with astrocytoma who underwent PSMA PET imaging for tumor detection. We retrospectively analyzed the records of 4 male and 2 female patients (mean age, 53.2 ± 13.2) who underwent PSMA PET imaging between March and September 2023. PET interpretation showed increased Ga-PSMA-11 accumulation in all patients with a mean SUV max of 3.11 ± 1.8. This series underscores PSMA PET's potential for CNS neoplasm detection.


Subject(s)
Central Nervous System Neoplasms , Gallium Isotopes , Positron-Emission Tomography , Humans , Male , Middle Aged , Female , Central Nervous System Neoplasms/diagnostic imaging , Glutamate Carboxypeptidase II/metabolism , Aged , Gallium Radioisotopes , Retrospective Studies , Adult , Edetic Acid/analogs & derivatives , Oligopeptides , Antigens, Surface/metabolism
9.
J Nucl Med ; 65(6): 904-908, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38637137

ABSTRACT

177Lu-PSMA therapy is an effective treatment in patients with metastatic castration-resistant prostate cancer. SUVmean is a valuable screening biomarker to assess the suitability for 177Lu-PSMA therapy but requires quantitative software. This study aims to develop a simple, clinically applicable prostate-specific membrane antigen PET/CT score that encompasses the elements of SUVmean without requiring additional quantification. Methods: Datasets from ethics-approved trials of patients with metastatic castration-resistant prostate cancer after androgen receptor signaling inhibition and taxane chemotherapy (or unfit for taxane), who were treated with 177Lu-PSMA-617 and 177Lu-PSMA I&T with a pretreatment screening with 68Ga-PSMA-11 PET/CT, and clinical outcome data, including a prostate-specific antigen (PSA) 50% response rate (PSA50), PSA progression-free survival (PSA-PFS), and overall survival (OS), were included. The screening 68Ga-PSMA-11 PET/CT of all participants was analyzed both semiquantitatively and visually. Semiquantitative analysis was used to derive the SUVmean Visual analysis of the 68Ga-PSMA-11 PET/CT images involved a binary visual heterogeneity assessment (homogeneous or heterogeneous), allocating a tumor SUVmax range (<15, 15-29, 30-49, 50-79, or ≥80). A 4-category score incorporating both heterogeneity and intensity of tumors (HIT) was then developed as a combination of heterogeneity and intensity (SUVmax range). The SUVmax was less than 15 for score 1, 15-79 with heterogeneous intensity for score 2, 15-79 with homogeneous intensity for score 3, and 80 or greater for score 4. This score was evaluated according to clinical outcomes (PSA50, PSA-PFS, and OS) and compared with SUVmean Results: Data from 139 participants were analyzed. In total, 75 (54%) patients achieved a PSA50 with a median PSA-PFS of 5.5 mo (95% CI, 4.1-6.0 mo) and an OS of 13.5 mo (95% CI, 11.1-17.9 mo). SUVmean was associated with PSA50 and survival outcomes when analyzed as a continuous variable or as quartiles. The PSA50 for HIT scores 1-4 was 0%, 39%, 65%, and 76%, respectively. The HIT score was strongly related to PSA-PFS and OS (log-rank test, P < 0.001 and P = 0.002). The median PSA-PFS for HIT scores 1-4 was 1.0, 4.1, 6.0, and 8.5, respectively, and the median OS was 7.6, 12.0, 18.5, and 16.9 mo, respectively. Cohen κ between readers for the HIT score was 0.71. Conclusion: A prostate-specific membrane antigen PET/CT score incorporating HIT derived from tools on a standard PET workstation is comparable with quantitative SUVmean as a prognostic tool following 177Lu-PSMA therapy.


Subject(s)
Lutetium , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms, Castration-Resistant , Humans , Male , Lutetium/therapeutic use , Treatment Outcome , Aged , Prostatic Neoplasms, Castration-Resistant/diagnostic imaging , Prostatic Neoplasms, Castration-Resistant/radiotherapy , Middle Aged , Heterocyclic Compounds, 1-Ring/therapeutic use , Dipeptides/therapeutic use , Prostate-Specific Antigen , Edetic Acid/analogs & derivatives , Gallium Radioisotopes , Image Processing, Computer-Assisted , Gallium Isotopes
10.
J Nucl Med ; 65(6): 897-903, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38664016

ABSTRACT

Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors are both overexpressed in prostate cancer (PC) but may provide complementary information.68Ga-PSMA-R2 and 68Ga-NeoB (DOTA-p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-NH-CH[CH2-CH(CH3)2]2) are novel PET radiopharmaceuticals that were developed for theranostic use. In this phase II imaging study, we assessed the feasibility, safety, and diagnostic performance of 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI for detection of biochemically recurrent PC. Methods: We prospectively enrolled 27 men with suspected biochemically recurrent PC after initial treatment but noncontributory conventional imaging results (negative or equivocal findings on MRI, CT, and/or bone scan). Participants underwent 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI within 2 wk in noncontrolled order. The SUVmax of putative PC lesions was measured and compared with a composite reference standard (histopathology, follow-up imaging, prostate-specific antigen change). The SUVmax and SUVmean of background organs were measured. Vital signs were recorded before injection of the radiopharmaceuticals and after the scans. Adverse events were recorded up to 72 h after each scan. Results: The prostate-specific antigen level at enrollment was 3.5 ± 3.9 ng/mL (range, 0.3-13.5 ng/mL). 68Ga-NeoB PET/MRI detected 31 lesions in 18 patients (66.7%), whereas 68Ga-PSMA-R2 identified 20 lesions in 15 participants (55.6%). 68Ga-NeoB PET/MRI showed higher sensitivity (85.7% vs. 71.4%), accuracy (88.9% vs. 77.8%), and negative predictive value (66.7% vs. 50.0%) than 68Ga-PSMA-R2, whereas specificity and positive predictive value were equally high (100.0% for both). In 6 patients, 68Ga-NeoB PET/MRI identified 14 lesions that were false-negative on 68Ga-PSMA-R2 PET/MRI. The mean lesion SUVmax was 6.6 ± 3.2 (range, 2.9-13.2) for 68Ga-NeoB and 4.4 ± 1.5 (range, 2.6-8.8) for 68Ga-PSMA-R2 (P = 0.019). Overall lower uptake was noted in tumors and background organs for 68Ga-PSMA-R2. There were no significant changes in vital signs before and after the scans. No adverse events were reported in the 72-h period after scans. Conclusion: 68Ga-NeoB and 68Ga-PSMA-R2 are safe for diagnostic imaging. 68Ga-NeoB PET/MRI showed better diagnostic performance than 68Ga-PSMA-R2. 68Ga-PSMA-R2 showed overall lower uptake, equally in background organs and tumors, and might therefore not be an ideal theranostic compound. Further evaluation in larger cohorts is needed to confirm our preliminary data.


Subject(s)
Gallium Radioisotopes , Magnetic Resonance Imaging , Positron-Emission Tomography , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/metabolism , Aged , Prospective Studies , Positron-Emission Tomography/methods , Middle Aged , Gallium Isotopes , Oligopeptides , Recurrence , Neoplasm Recurrence, Local/diagnostic imaging , Aged, 80 and over , Radiopharmaceuticals , Edetic Acid/analogs & derivatives , Multimodal Imaging
11.
Nuklearmedizin ; 63(3): 199-206, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38580313

ABSTRACT

AIM: This study aimed to assess the impact of 68Ga-PSMA PET/CT on radiation treatment (RT) planning in prostate cancer patients with salvage (sRT) or definitive (dRT) radiotherapy. METHODS: 38 patients (27 sRT, median PSA 0.79 ng/ml (range 0.06-12.1); 11 dRT, median PSA 4.35 ng/ml (range 1.55-55.5) underwent 68Ga-PSMA PET/CT before RT. Influence of 68Ga-PSMA PET/CT on the extent of planning target volume (PTV) and addition of PET-based boosts were assessed. Median follow up was 12 months (range 3-24). RESULTS: 68Ga-PSMA PET/CT showed positive findings in 23/38 patients (8/23: local recurrence (LR), 11/23: nodal metastasis, 1/23: LR and nodal, 2/23: solitary bone metastasis, 1/23: oligometastatic nodal/ bone metastases). In sRT primary PTV was changed in 16/27 patients extending the PTV to the lymphatic drainage (10/16), PSMA-positive LR (3/16), bone metastases (2/16) and both nodal/bone metastases (1/16). PET-based increase of primary PTV was 116%. PET-based boosts were administered in 19/27 patients (8/19: local, 10/19: nodal, 1/19: both), median boost volume was 31.3 cm3 (range 17.2-80.2) (local) and 19.7 cm3 (range 3.0-109.3) (nodal). PTV was changed in 1/11 (9%) of dRT patients (extension of primary PTV to the lymphatic drainage (RT volume of 644.5 cm3), additional nodal boost (volume of 2.7 cm3, 23.1 Gy)). All patients showed biochemical response (mean PSA decrease 88.8 +/- 14.0%). Nadir PSA was reached 10 months (range 1-17) after end of RT (median 0.07 ng/ml, range 0.002-3.96). Within a median 12 months follow-up (range 3-22/8-24 in sRT/dRT), median PSA was 0.05 ng/ml (range 0.002-8.5) (sRT) and 0.26 ng/ml (range 0.02-2.68) (dRT). CONCLUSIONS: 68Ga-PSMA PET/CT influenced sRT planning in almost 63% and dRT in 9% of patients by change of PTV and additional boosts.


Subject(s)
Edetic Acid , Gallium Isotopes , Gallium Radioisotopes , Oligopeptides , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Radiotherapy Planning, Computer-Assisted , Humans , Male , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Aged , Radiotherapy Planning, Computer-Assisted/methods , Middle Aged , Edetic Acid/analogs & derivatives , Aged, 80 and over , Radiopharmaceuticals/therapeutic use , Treatment Outcome
12.
Int J Mol Sci ; 25(8)2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38673932

ABSTRACT

Platinum-containing chemotherapeutic drugs are efficacious in many forms of cancer but are dose-restricted by serious side effects, of which peripheral neuropathy induced by oxidative-nitrosative-stress-mediated chain reactions is most disturbing. Recently, hope has been raised regarding the catalytic antioxidants mangafodipir (MnDPDP) and calmangafodipir [Ca4Mn(DPDP)5; PledOx®], which by mimicking mitochondrial manganese superoxide dismutase (MnSOD) may be expected to overcome oxaliplatin-associated chemotherapy-induced peripheral neuropathy (CIPN). Unfortunately, two recent phase III studies (POLAR A and M trials) applying Ca4Mn(DPDP)5 in colorectal cancer (CRC) patients receiving multiple cycles of FOLFOX6 (5-FU + oxaliplatin) failed to demonstrate efficacy. Instead of an anticipated 50% reduction in the incidence of CIPN in patients co-treated with Ca4Mn(DPDP)5, a statistically significant increase of about 50% was seen. The current article deals with confusing differences between early and positive findings with MnDPDP in comparison to the recent findings with Ca4Mn(DPDP)5. The POLAR failure may also reveal important mechanisms behind oxaliplatin-associated CIPN itself. Thus, exacerbated neurotoxicity in patients receiving Ca4Mn(DPDP)5 may be explained by redox interactions between Pt2+ and Mn2+ and subtle oxidative-nitrosative chain reactions. In peripheral sensory nerves, Pt2+ presumably leads to oxidation of the Mn2+ from Ca4Mn(DPDP)5 as well as from Mn2+ in MnSOD and other endogenous sources. Thereafter, Mn3+ may be oxidized by peroxynitrite (ONOO-) into Mn4+, which drives site-specific nitration of tyrosine (Tyr) 34 in the MnSOD enzyme. Conformational changes of MnSOD then lead to the closure of the superoxide (O2•-) access channel. A similar metal-driven nitration of Tyr74 in cytochrome c will cause an irreversible disruption of electron transport. Altogether, these events may uncover important steps in the mechanism behind Pt2+-associated CIPN. There is little doubt that the efficacy of MnDPDP and its therapeutic improved counterpart Ca4Mn(DPDP)5 mainly depends on their MnSOD-mimetic activity when it comes to their potential use as rescue medicines during, e.g., acute myocardial infarction. However, pharmacokinetic considerations suggest that the efficacy of MnDPDP on Pt2+-associated neurotoxicity depends on another action of this drug. Electron paramagnetic resonance (EPR) studies have demonstrated that Pt2+ outcompetes Mn2+ and endogenous Zn2+ in binding to fodipir (DPDP), hence suggesting that the previously reported protective efficacy of MnDPDP against CIPN is a result of chelation and elimination of Pt2+ by DPDP, which in turn suggests that Mn2+ is unnecessary for efficacy when it comes to oxaliplatin-associated CIPN.


Subject(s)
Antineoplastic Agents , Manganese , Oxaliplatin , Peripheral Nervous System Diseases , Platinum , Humans , Antineoplastic Agents/adverse effects , Edetic Acid/analogs & derivatives , Manganese/adverse effects , Nitrosative Stress/drug effects , Oxaliplatin/adverse effects , Oxaliplatin/pharmacology , Oxidative Stress/drug effects , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/metabolism , Platinum/adverse effects , Pyridoxal Phosphate/analogs & derivatives , Pyridoxal Phosphate/pharmacology , Pyridoxal Phosphate/metabolism , Superoxide Dismutase/metabolism , Clinical Trials, Phase III as Topic
13.
Hell J Nucl Med ; 27(1): 16-26, 2024.
Article in English | MEDLINE | ID: mdl-38629815

ABSTRACT

OBJECTIVE: Recently, gallium-68-prostate-specific membrane antigen-11 (68Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) has become a key imaging method in prostate carcinoma staging and biochemical progression, with varying sensitivities in different studies (from 40% to 80%). After four years of experience with 68Ga-PSMA-11 PET/CT, we found that it is possible to detect lesions with increased PSMA expression in patients with undetectable prostate specific antigen (PSA) levels after radical prostatectomy. The key questions we wanted to answer were as follows: if those lesions were malignant and could the early detection of those malignant lesions have a role in patient management? We aimed to identify and follow up PSMA-positive findings for a period of 4 years in patients with prostate cancer after radical prostatectomy and undetectable PSA values at the time of the examination. We also explored false-positive lesions in detail. SUBJECTS AND METHODS: The study included all patients who underwent radical prostatectomy and had undetectable PSA values <0.05ng/mL and who underwent 68Ga-PSMA-11 PET/CT between July 2019 and December 2019. We performed 220 studies and found 40 patients with these characteristics; these patients were included in this study. All of them were followed up until July 2023. Any finding with increased radiopharmaceutical accumulation above the background activity in the respective area was considered a false positive. Prostate-specific membrane antigen accumulation in established lesions was assessed semi-quantitatively by the maximum standardized uptake value (SUVmax) and qualitatively by the four-point visual scale proposed in the E-PSMA recommendations. RESULTS: We found 15/40 (37.5%) patients with PSMA-positive findings. These were predominantly bone changes without a corresponding CT abnormality or discrete cystic or osteoblastic lesions with above-background increased PSMA expression. The mean SUVmax of these non-specific lesions was 3.02 (SD 2.86). After 3.5-4 years of follow-up, biochemical progression was found in only two of the patients.The great sensitivity of the method nowadays is a powerful engine for the development of new therapeutic options. On the other side, the lower specificity due to false positive findings, if misinterpreted, might lead to switching to a higher stage, with the planned radical treatment replaced by palliative treatment. CONCLUSION: The presence of 68Ga-PSMA-11 PET/CT-positive findings in patients after radical prostatectomy and an undetectable PSA had a low predictive value for future progression. The interpretation of 68Ga-PSMA-11 PET/CT should always include a complex assessment of the clinical setting-the risk group, PSA value and degree of PSMA accumulation in the lesions. In these situations, further clarification of PSMA-positive findings is appropriate before deciding to change treatment.


Subject(s)
Positron Emission Tomography Computed Tomography , Prostate-Specific Antigen , Prostatectomy , Prostatic Neoplasms , Aged , Humans , Male , Middle Aged , Edetic Acid/analogs & derivatives , False Positive Reactions , Gallium Isotopes , Gallium Radioisotopes , Oligopeptides , Prognosis , Prostate-Specific Antigen/blood , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , Prostatic Neoplasms/metabolism
14.
Clin Nucl Med ; 49(6): 587-588, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38557426

ABSTRACT

ABSTRACT: Prostate carcinoma (PC) is the second most common malignant tumor in males globally. The metastatic spread of PC usually involves the pelvic and abdominal lymph nodes and the skeletal system. Cutaneous metastases are exceedingly uncommon and typically manifest themselves late in the disease course, considered as ominous sign with limited treatment options and a poor prognosis. We describe a patient wherein 68 Ga-PSMA-11 PET/CT detected multiple uncommon metastatic sites in the cutaneous region of the scrotum, penis, and thigh, as well as in the subcutaneous region of anterior abdominal wall, and in bilateral adrenal glands. These findings served as a theranostic tool for selecting 177 Lu-PSMA-617 treatment for these extremely rare metastatic sites.


Subject(s)
Adrenal Gland Neoplasms , Gallium Isotopes , Gallium Radioisotopes , Lutetium , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Skin Neoplasms , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Adrenal Gland Neoplasms/diagnostic imaging , Adrenal Gland Neoplasms/secondary , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/pathology , Heterocyclic Compounds, 1-Ring/therapeutic use , Edetic Acid/analogs & derivatives , Disease Progression , Radioisotopes/therapeutic use , Dipeptides/therapeutic use , Aged , Oligopeptides , Subcutaneous Tissue/diagnostic imaging , Subcutaneous Tissue/pathology , Precision Medicine
15.
J Emerg Manag ; 22(1): 45-52, 2024.
Article in English | MEDLINE | ID: mdl-38533699

ABSTRACT

BACKGROUND: A business continuity plan (BCP) facilitates the performance of primary functions during emergencies or other situations that can disrupt normal operations. If risk management is done analytically, a business impact analysis (BIA), according to ISO 22301 certification, makes it possible to define the best strategy for supporting the company's assets and image, optimizing the operational efficiency of service recovery and redesigning spaces for health. Since 2015, our healthcare company has embarked on a certification process for all sectors and activities through the implementation and development of diagnostic and therapeutic paths for operational diagnos-tic-therapeutic-assistance pathways (PDTAs). PDTA processes are all certified by the ISO 9001:2015 management system hospital. Our hospital is the first healthcare company to have obtained ISO 22301:2019 certification concerning PDTA processes, offering patients the highest standards of quality and safety of care in emergency medical services. METHODS: The formal BCP process includes several steps prior to the creation of a BCP: create a BCP team, conduct a BIA, determine the continuity plan by using the results of the analyses, and conduct training and exercises to educate staff and improve the BCP. RESULTS: From the BIA analysis, the team identified the time-employee PDTAs in company paths under emergency and urgency: acute ST-elevation myocardial infarction (STEMI), TRAUMA, and STROKE, providing for a planning path that took advantage of the duration of approximately 12 months. This path included the creation of structural procedures, the redefinition and updating of the PDTA in the light of the BCP, the preparation of exercises aimed at guaranteeing the business continuity objectives, and, finally, the awareness of our stakeholders regarding its correct application. CONCLUSIONS: With a business continuity management (BCM) system, companies take preventative measures to ensure they can start operations again quickly in an emergency. An exhaustive BIA in a hospital company reveals the effects when processes fail, how critical each process is for the company, and the amount of time required to get up and running again, thus providing the organization with important information for risk management. The measures for handling risks derived from this analysis are incorporated into a BCM system where the emergency plans are defined, too, so that business operations continue even in the event of an emergency.


Subject(s)
Disaster Planning , Edetic Acid/analogs & derivatives , Emergency Medical Services , Humans , Commerce , Hospitals
16.
J Med Chem ; 67(6): 4793-4803, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38450559

ABSTRACT

Bone metastasis in cancer patients is a major disease advancement for various types of cancer. Previously, [68Ga]Ga-HBED-CC-bisphosphonate ([68Ga]Ga-P15-041) showed excellent bone uptake and efficient detection of bone metastasis in patients. To accommodate different α- or ß--emitting metals for radionuclide therapy, a novel DOTA-HBED-CC-bisphosphonate (P15-073, 1) was prepared and the corresponding [68Ga]Ga-1 and [177Lu]Lu-1 were successfully synthesized in high yields and purity. Gallium-68 conjugation to HBED-CC at room temperature and lutetium-177 conjugation to DOTA at 95 °C were verified in model compounds through secondary mass confirmation. These bisphosphonates, [68Ga]Ga-1 and [177Lu]Lu-1, displayed high binding affinity to hydroxyapatite in vitro. After an iv injection, it showed excellent uptake in the spine of normal mice, and micro-PET/CT imaging of nude mice model of bone metastasis showed high bone uptake in tumor tissue. The results indicated that [68Ga]Ga/[177Lu]Lu-1 holds promise as a theranostic radioligand agent for managing cancer bone metastases.


Subject(s)
Bone Neoplasms , Edetic Acid/analogs & derivatives , Gallium Radioisotopes , Heterocyclic Compounds, 1-Ring , Humans , Mice , Animals , Positron Emission Tomography Computed Tomography , Diphosphonates/therapeutic use , Precision Medicine , Mice, Nude , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/drug therapy
17.
Clin Nucl Med ; 49(6): e274-e275, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38537177

ABSTRACT

ABSTRACT: A 76-year-old man undergoing hormone therapy for prostate cancer was referred for 68 Ga-PSMA-11-PET (PSMA PET) due to persistently detectable PSA level. No PSMA-positive tumor lesions were detected, so a delayed phase imaging was performed, which revealed focal PSMA uptake in the right seminal vesicle together with contrast accumulation on excretory phase contrast-enhanced CT. These findings were finally determined to be secondary to urinary reflux as a consequence of a prostatic enucleation he had undergone 5 months earlier following an episode of acute urinary retention.


Subject(s)
Antigens, Surface , Gallium Isotopes , Gallium Radioisotopes , Positron-Emission Tomography , Seminal Vesicles , Humans , Male , Aged , Seminal Vesicles/diagnostic imaging , Edetic Acid/analogs & derivatives , Prostatic Neoplasms/diagnostic imaging , Oligopeptides , Glutamate Carboxypeptidase II/metabolism
18.
Reprod Biol Endocrinol ; 22(1): 30, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38491531

ABSTRACT

BACKGROUND: It is generally beneficial and recommended that dichorionic triamniotic (DCTA) triplet pregnancies be reduced to monochorionic (MC) twin or singleton pregnancies after assisted reproductive technology (ART). However, some infertile couples still have a firm desire to retain twins. For this reason, the best foetal reduction strategies need to be available for infertile couples and clinicians. Given that data on the elective reduction of DCTA triplet pregnancies to twin pregnancies are scarce, we investigated the outcomes of elective reduction of DCTA triplet pregnancies through the retrospective analysis of previous data. METHOD: Patients with DCTA triplet pregnancies who underwent elective foetal reduction between January 2012 and June 2020 were recruited. A total of 67 eligible patients with DCTA triplet pregnancies were divided into two groups: a DCTA-to-dichorionic diamniotic (DCDA) twin group (n = 38) and a DCTA-to-monochorionic diamniotic (MCDA) twin group (n = 29); the basic clinical data of the two groups were collected for comparison. RESULTS: Compared with the DCDA-to-MCDA twin group, the DCTA-to-DCDA twin group had lower rates of complete miscarriage (7.89% versus 31.03%, p = 0.014), early complete miscarriage (5.26% versus 24.14%, p = 0.034), late preterm birth (25.71% versus 65.00%, p = 0.009) and very low birth weight (0 versus 11.11%, p = 0.025). In addition, the DCTA-to-DCDA twin group had higher rates of full-term delivery (65.71% versus 25.00%, p = 0.005), survival (92.11% versus 68.97%, p = 0.023), and taking the babies home (92.11% versus 68.97%, p = 0.023) than did the DCTA-to-MCDA twin group. In terms of neonatal outcomes, a significantly greater gestational age (38.06 ± 2.39 versus 36.28 ± 2.30, p = 0.009), average birth weight (3020.77 ± 497.33 versus 2401.39 ± 570.48, p < 0.001), weight of twins (2746.47 ± 339.64 versus 2251.56 ± 391.26, p < 0.001), weight of the larger neonate (2832.94 ± 320.58 versus 2376.25 ± 349.95, p < 0.001) and weight of the smaller neonate (2660.00 ± 345.34 versus 2126.88 ± 400.93, p < 0.001) was observed in the DCTA-to-DCDA twin group compared to the DCTA-to-MCDA twin group. CONCLUSION: The DCTA-to-DCDA twin group had better pregnancy and neonatal outcomes than the DCTA-to-MCDA twin group. This reduction approach may be beneficial for patients with dichorionic triamniotic triplet pregnancies who have a strong desire to have DCDA twins.


Subject(s)
Abortion, Spontaneous , Edetic Acid/analogs & derivatives , Pregnancy, Triplet , Premature Birth , Pregnancy , Infant , Female , Infant, Newborn , Humans , Retrospective Studies , Pregnancy Reduction, Multifetal , Pregnancy, Twin , Reproductive Techniques, Assisted , Pregnancy Outcome
19.
Clin Nucl Med ; 49(6): 582-583, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38389216

ABSTRACT

ABSTRACT: Leptomeningeal carcinomatosis in prostate cancer is extremely rare. Because of the low overall penetration of drugs into the brain and the prolonged survival of castration-resistant prostate cancer (CRPC) patients, a special attention should be paid to the appearance of neurological symptoms in long-term CRPC survivors. A patient suffering from a CRPC with bone metastases underwent 4 cycles of 177 Lu-PSMA (prostate-specific membrane antigen)-617. Starting from the third cycle, he reported an increasing feeling of a permanent hangover. A 68 Ga-PSMA-11 brain PET/MRI was carried out after the fourth cycle. It revealed intraparenchymatous brain metastases with intense uptake and evidences of leptomeningeal carcinomatosis.


Subject(s)
Gallium Isotopes , Gallium Radioisotopes , Lutetium , Magnetic Resonance Imaging , Positron-Emission Tomography , Prostate-Specific Antigen , Humans , Male , Dipeptides , Heterocyclic Compounds, 1-Ring , Multimodal Imaging , Edetic Acid/analogs & derivatives , Aged , Prostatic Neoplasms, Castration-Resistant/diagnostic imaging , Radioisotopes , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/secondary , Brain/diagnostic imaging
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