Active Lumbar Spondylodiscitis on [68Ga]Ga-PSMA-11 PET/CT Mimicking Bone Metastasis

We report a [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) scan of a 71-year-old man with metastatic castration-resistant prostate cancer (mCRPC) and concomitant active lumbar spondylodiscitis, both PSMA-positive on a PET/CT scan. This interesting image should advise colleagues to consider spondylodiscitis as a differential diagnosis of PSMA-positive findings in the spine, particularly if intervertebral space and soft tissue are involved

Genetic polymorphism and drug interactions: their importance in the treatment of pain

Résumé: Objectif: Evaluer ľimpact de certains polymorphismes génétiques sur la variabilité de réponse aux analgésiques. Sources: Revue systématique par recherche informatisée structurée dans la base Medline (1966-2004), mots clés : pharmacogénétique, polymorphisme, cytochrome P450 (CYP), glycoprotéine P (P-gp), douleur, antalgiques, opiacés, morphine, codéine, tramadol, anti-inflammatoires non stéroïdiens (AINS). Sélection ďarticles de langue anglaise et française. Bibliographies ďarticles pertinents également sélectionnées. Constatations principales: La plupart des analgésiques sont métabolisés via les isoenzymes du CYP soumis à un polymorphisme génétique. Les AINS sont métabolisés par le CYP2C9; les opioïdes qualifiés de " faibles ” (codéine, tramadol), antidépresseurs et dextrométhorphane par le CYP2D6 et certains opioïdes "forts” (buprénorphine, méthadone ou fentanyl) par le CYP3A4/5. Après administration de doses usuelles, une toxicité médicamenteuse ou, au contraire, une inefficacité thérapeutique peut survenir en fonction du polymorphisme et de la substance. Les interactions médicamenteuses, en mimant les défauts génétiques du fait de ľexistence ďinhibiteurs et ďinducteurs des CYP, participent également à la variabilité de réponse aux analgésiques. Certains opioïdes sont substrats de la P-gp, transporteur transmembranaire également soumis à un polymorphisme génétique. La P-gp ne pourrait toutefois jouer chez ľhomme qu'un röle modulateur mineur sur les effets centraux de la morphine, de la méthadone et du fentanyl. Conclusion: La pharmacogénétique devrait dans un avenir proche permettre ďoptimaliser la thérapeutique en individualisant ľapproche analgésique médicamenteuse et en améliorant la sécurité ďemploi et ľefficacité de nombreux analgésiques. Ľutilité clinique de ces approches individualisées devra être démontrée par des études et des analyses pharmacoéconomiques appropriée

Systemic Mastocytosis Treatment with Midostaurin: [18F]FDG PET/CT as a Potential Monitoring Tool for Therapy Outcome

We report the case of a 68-year-old patient with diagnosed systemic mastocytosis and histopathologically confirmed manifestations in the stomach and intestinal tract who underwent 18FFluorodeoxyglucose ([18F]FDG) positron-emission tomography/computed tomography (PET/CT) pre- and post-6-month therapy with midostaurin, an established tyrosine kinase inhibitor. Posttherapeutic [18F]FDG PET/CT showed decreased multifocal tracer uptake in the known lesions in the gastrointestinal tract, which was consistent with relief of the patient’s symptoms and decrease in serum tryptase level. [18F]FDG PET/CT may thus be considered a potential method for monitoring the outcome of midostaurin therapy in systemic mastocytosis

Histologically Confirmed Testicular Metastasis Revealed by [89Zr]Zr-PSMA-617 PET/CT in a Patient with Biochemical Recurrence of Prostate Cancer and Negative Conventional PSMA PET/CT Imaging

We present an interesting image of a testicular metastasis from prostate cancer revealed by [ 89Zr]Zr-PSMA-617 PET/CT imaging in a 70-year-old man with biochemical recurrence and negative conventional [68Ga]Ga-PSMA-11 PET/CT imaging. This case should encourage the consideration of [ 89Zr]Zr-PSMA-617 PET/CT if conventional PSMA PET/CT imaging had failed to localize biochemical recurrence, and may remind colleagues of this rare but potential metastatic localization in this setting

Strongly Radioiodine-Positive Pancreatic Adenocarcinoma Mimicking Metastasis of Differentiated Thyroid Cancer

We present an interesting image of a strikingly intense radioiodine accumulation of a histologically proven pancreatic adenocarcinoma mimicking metastasis of differentiated thyroid cancer in a 63-year-old woman with recurrence of papillary thyroid carcinoma undergoing radioiodine therapy. This interesting image should draw attention to considering pancreatic adenocarcinoma in radioiodine-positive pancreatic lesions

PSMA-Positive Follicular Thyroid Carcinoma Incidentally Detected by [68Ga]Ga-PSMA-11 PET/CT: Correlation with Immunohistology Confirms Neovascular PSMA-Expression

We present an interesting image of an intense PSMA-positive follicular thyroid carci noma incidentally detected by [68Ga]Ga-PSMA-11 PET/CT in a 76-year-old man with biochemical recurrence of prostate cancer. Immunohistochemical staining demonstrated PSMA expression in the endothelial cells of tumor tissue. This interesting image should remind colleagues to consider malignant thyroid neoplasia in PSMA-positive thyroid lesions

Addition of Standard Enzalutamide Medication Shows Synergistic Effects on Response to [177Lu]Lu-PSMA-617 Radioligand Therapy in mCRPC Patients with Imminent Treatment Failure—Preliminary Evidence of Pilot Experience

Well-received strong efficacy of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) does not prevent patients from either early or eventual disease progression under this treatment. In this study, we investigated co-medication with enzalutamide as a potential re-sensitizer for PSMA-RLT in patients with imminent treatment failure on standard 177Lu-based PSMA-RLT. Ten mCRPC patients who exhibited an insufficient response to conventional [177Lu]Lu PSMA-617 RLT received oral medication of enzalutamide 160 mg/d as an adjunct to continued PSMA RLT. Prostate-specific antigen (PSA) and standard toxicity screening lab work-up were performed to assess the treatment efficacy and safety in these individuals. The mean PSA increase under PSMA-RLT before starting the re-sensitizing procedure was 22.4 ± 26.5%. After the introduction of enzalutamide medication, all patients experienced a PSA decrease, –43.4 ± 20.0% and –48.2 ± 39.0%, after one and two cycles of enzalutamide-augmented PSMA-RLT, respectively. A total of 70% of patients (7/10) experienced partial remission, with a median best PSA response of –62%. Moreover, 5/6 enzalutamide-naïve patients and 2/4 patients who had previously failed enzalutamide exhibited a partial remission. There was no relevant enzalutamide-induced toxicity observed in this small cohort. This pilot experience suggests the synergistic potential of adding enzalutamide to PSMA-RLT derived from the intra-individual comparison of 177Lu-based PSMA-RLT ± enzalutamide

A Structure-Activity Relationship Study of Bimodal BODIPY-Labeled PSMA-Targeting Bioconjugates

The aim of this study was to identify a high-affinity BODIPY peptidomimetic that targets the prostate-specific membrane antigen (PSMA) as a potential bimodal imaging probe for prostate cancer. For the structure-activity study, several BODIPY (difluoroboron dipyrromethene) derivatives with varying spacers between the BODIPY dye and the PSMA Glu-CO-Lys binding motif were prepared. Corresponding affinities were determined by competitive binding assays in PSMA-positive LNCaP cells. One compound was identified with comparable affinity (IC50=21.5±0.1 nM) to Glu-CO-Lys-Ahx-HBED-CC (PSMA-11) (IC50=18.4±0.2 nM). Radiolabeling was achieved by Lewis-acid-mediated 19F/18F exchange in moderate molar activities (∼0.7 MBq nmol−1) and high radiochemical purities (>99 %) with mean radiochemical yields of 20–30 %. Cell internalization of the 18F-labeled high-affinity conjugate was demonstrated in LNCaP cells showing gradual increasing PSMA-mediated internalization over time. By fluorescence microscopy, localization of the high-affinity BODIPY-PSMA conjugate was found in the cell membrane at early time points and also in subcellular compartments at later time points. In summary, a high-affinity BODIPY-PSMA conjugate has been identified as a suitable candidate for the development of PSMA-specific dual-imaging agents

Upregulation of PSMA Expression by Enzalutamide in Patients with Advanced mCRPC

In this study, we investigated upregulation of prostate-specific membrane antigen (PSMA) by enzalutamide in a cohort (n = 30) of patients with advanced metastatic castration-resistant prostate cancer (mCRPC). Patients were examined by [68Ga]Ga-PSMA-11 PET/CT pre- and post-enzalutamide medication (mean 13 ± 7 days). Imaging results were compared based on quantification of wholebody PSMA tumor burden: total lesion PSMA (TLP) and normalized TLP values to liver (TLP-LR) and to parotid gland (TLP-PR). In addition, lesion-based analyses were performed. The median (mean) increases in TLP, TLP-LR and TLP-PR after enzalutamide medication were 10.1% (20.2%), 29.5% (34.8%) and 27.6% (24.4%), respectively. These increases were statistically significant (p = 0.002, p < 0.001, and p < 0.001), while prostate-specific antigen (PSA) serum values did not change significantly (p = 0.483). The increase was independent of prior patient exposure to enzalutamide. SUVmax increased substantially (>10%) in 49.6% of target lesions. The relative change was significantly higher in the subgroup of lesions with SUVmax < 10 (p < 0.001). In conclusion, short-term enzalutamide medication significantly increases PSMA expression in patients with mCRPC, irrespective of prior enzalutamide exposure. The relative PSMA upregulation effect seems to be more pronounced in lesions with only moderate baseline PSMA expression. Enzalutamide may provide a potential enhancer medication for PSMA-targeted radioligand therapy

Detection efficacy of [89Zr]Zr-PSMA-617 PET/CT in [68Ga]Ga-PSMA-11 PET/CT-negative biochemical recurrence of prostate cancer

Rationale In patients with biochemical recurrence of prostate cancer (BCR), preliminary data suggest that prostate-specifc membrane antigen (PSMA) ligand radiotracers labeled with zirconium-89 (89Zr; half-life ~ 78.41 h), which allow imaging≥24 h post-injection, detect suspicious lesions that are missed when using tracers incorporating short-lived radionuclides. Materials and methods To confrm [ 89Zr]Zr-PSMA-617 positron emission tomography/computed tomography (PET/CT) detection efcacy regarding such lesions, and compare quality of 1-h, 24-h, and 48-h [ 89Zr]Zr-PSMA-617 scans, we retrospectively analyzed visual fndings and PET variables refecting lesional [ 89Zr]Zr-PSMA-617 uptake and lesion-to-background ratio. The cohort comprised 23 men with BCR post-prostatectomy, median (minimum–maximum) prostate-specifc antigen (PSA) 0.54 (0.11–2.50) ng/mL, and negative [ 68Ga]Ga-PSMA-11 scans 40±28 d earlier. Primary endpoints were percentages of patients with, and classifcations of, suspicious lesions. Results Altogether, 18/23 patients (78%) had 36 suspicious lesions (minimum–maximum per patient: 1–4) on both 24-h and 48-h scans (n=33 lesions) or only 48-h scans (n=3 lesions). Only one lesion appeared on a 1-h scan. Lesions putatively represented local recurrence in 11 cases, and nodal or bone metastasis in 21 or 4 cases, respectively; 1/1 lesion was histologically confrmed as a nodal metastasis. In all 15 patients given radiotherapy based on [ 89Zr]Zr-PSMA-617 PET/CT, PSA values decreased after this treatment. Comparison of PET variables in 24-h vs 48-h scans suggested no clear superiority of either regarding radiotracer uptake, but improved lesion-to-background ratio at 48 h. Conclusions In men with BCR and low PSA, [ 89Zr]Zr-PSMA-617 PET/CT seems efective in fnding prostate malignancy not seen on [ 68Ga]Ga-PSMA-11 PET/CT. The higher detection rates and lesion-to-background ratios of 48-h scans versus 24-h scans suggest that imaging at the later time may be preferable. Prospective study of [ 89Zr]Zr-PSMA-617 PET/CT is warranted