[18F]DCFPyL PET/CT for Imaging of Prostate Cancer

Prostate-specific membrane antigen (PSMA)-directed positron emission tomography (PET) has gained increasing interest for imaging of men affected by prostate cancer (PC). In recent years, 68Ga-labeled PSMA compounds have been widely utilized, although there is a trend towards increased utilization of 18F-labeled agents. Among others, [18F]DCFPyL (piflufolastat F 18, PYLARIFY) has been tested in multiple major trials, such as OSPREY and CONDOR, which provided robust evidence on the clinical utility of this compound for staging, restaging, and change in management. Recent explorative prospective trials have also utilized [18F]DCFPyL PET/CT for response assessment, e.g., in patients under abiraterone or enzalutamide, rendering this 18F-labeled PSMA radiotracer as an attractive biomarker for image-guided strategies in men with PC. After recent approval by the U.S. Food and Drug Administration, one may expect more widespread use, not only in the U.S., but also in Europe in the long term. In the present review, we will provide an overview of the current clinical utility of [18F]DCFPyL in various clinical settings for men with PC.

Resveratrol treatment does not reduce arterial inflammation in males at risk of type 2 diabetes: a randomized crossover trial

Purpose Resveratrol has shown promising anti-inflammatory effects in in vitro and animal studies. We aimed to investigate this effect on arterial inflammation in vivo. Methods This was an additional analysis of a double-blind randomized crossover trial which included eight male subjects with decreased insulin sensitivity who underwent an 18F-fluoroxyglucose (18F-FDG) PET/CT after 34 days of placebo and resveratrol treatment (150 mg/day). 18F-FDG uptake was analyzed in the carotid arteries and the aorta, adipose tissue regions, spleen, and bone marrow as measures for arterial and systemic inflammation. Maximum target-to-background ratios (TBRmax) were compared between resveratrol and placebo treatment with the non-parametric Wilcoxon signed-rank test. Median values are shown with their interquartile range. Results Arterial 18F-FDG uptake was non-significantly higher after resveratrol treatment (TBRmax all vessels 1.7 (1.6–1.7)) in comparison to placebo treatment (1.5 (1.4–1.6); p=0.050). Only in visceral adipose tissue, the increase in 18F-FDG uptake after resveratrol reached statistical significance (p=0.024). Furthermore, CRP-levels were not significantly affected by resveratrol treatment (p=0.091). Conclusions Resveratrol failed to attenuate arterial or systemic inflammation as measured with 18F-FDG PET in subjects at risk of developing type 2 diabetes. However, validation of these findings in larger human studies is needed.

Treatment outcome and identification of factors influencing overall survival after Lu-177-PSMA-617 radioligand therapy in metastatic prostate cancer

Objective To examine the clinical benefit of Lu-177-PSMA-617 radioligand therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods Between November 2014 and December 2018, a total of 56 consecutive patients (median age 69.5 years; range 55–84 years) with mCRPC were included in this retrospective analysis. Patients received between 1 and 4 therapy cycles with a mean activity of 6.8 GBq per cycle. Biochemical response was evaluated using Prostate Cancer Working Group Criteria 3 (PCWG 3). Survival was assessed using Kaplan-Meier estimates and Cox proportional hazards regression analysis. This retrospective study was approved by the local ethics committee. Results A total of 139 treatment cycles with Lu-177-PSMA-617 were performed. A decline of 50% or more of prostate-specific antigen (PSA) level occurred in 54% and a PSA decline of any amount in 65% of patients. The estimated median overall survival (OS) was 16 months, in the chemotherapy subgroup 14 months. A longer OS was associated with a PSA-decline ≥50%, more than 2 cycles of therapy, cumulative activity >15 GBq and an initial alkaline phosphatase ≤ 220 [U/l]. These identified predictors remained significant on uni- and multivariate Cox regression analysis. Moreover, 40% of the patients who were non-responders after the first therapy cycle turned into responders after the second one. Conclusion PSA-decline ≥50%, a cumulative activity >15 GBq and an initial alkaline phosphatase ≤ 220 [U/l] were identified as key predictors of prolonged OS in patients with mCRPC. In contrast rapid clinical deterioration mostly due to skeletal carcinomatosis resulted in early treatment failure.

Bestrahlungsplanung und Dosisverifikation für die kombinierte interne und externe Strahlentherapie (CIERT)

Zusammenfassung Ziel Die kombinierte interne und externe Radiotherapie (CIERT) mittels offenen Radionukliden und externer Bestrahlung ermöglicht die Ausnutzung der Vorteile beider Bestrahlungsansätze. Hierzu zählen steile Dosisgradienten und eine geringe Normalgewebstoxizität durch die Bestrahlung mit offenen Radionukliden sowie die homogene Dosisdeposition innerhalb des Tumors durch externe Bestrahlung. Für eine kombinierte Bestrahlungsplanung soll eine Infrastruktur zur Berücksichtigung der Dosisbeiträge aus beiden Modalitäten geschaffen werden. Anschließend soll die physikalische Verifikation der Dosisverteilung messtechnisch mittels OSL-Detektoren erfolgen. Methode Die interne Bestrahlung erfolgte durch Re-188 in einem Zylinderphantom mit drei zylindrischen Einsätzen. Nach Akquisition von SPECT-Aufnahmen wurde die interne Dosis mittels der Software STRATOS berechnet und als DICOM-RT-Datensatz exportiert. Mittels der Planungssoftware Pinnacle wurde diese Dosisverteilung als Vorbestrahlung berücksichtigt und die externe Bestrahlung mit 6 MV Photonen geplant. Die Messung der Dosisbeiträge erfolgte mittels OSL-Detektoren aus Berylliumoxid für die kombinierte Bestrahlung und für beide Modalitäten getrennt. Ergebnisse Die geplante Kombinationsbestrahlung mit 1 Gy, 2 Gy und 4 Gy konnte innerhalb der Messunsicherheit der Detektoren sowohl für die getrennten als auch die kombinierte interne und externe Bestrahlung verifiziert werden. Das mittlere Ansprechvermögen der Detektoren bei der internen Bestrahlung mit Re-188 betrug dabei (88,6 ± 2,4) % gegenüber der Kalibrierung mit 200 kV Röntgenstrahlen, wogegen das Ansprechvermögen für 6 MV Photonen bei (146,0 ± 4,9) % lag. Schlussfolgerung Es wurde ein Ablaufschema für die Bestrahlungsplanung bei der kombinierten internen und externen Radiotherapie entwickelt und erfolgreich getestet. Messtechnisch konnte die Dosisverifikation mittels OSL-Detektoren erfolgreich umgesetzt werden, so dass die physikalisch-technischen Grundlagen für die Dosimetrie bei Kombinationsbestrahlungen gelegt sind.

Diagnostic Value of Bone SPECT/CT Using 99mTc-Methylene Diphosphonate in Patients with Unspecified Chest Wall Pain

Purpose We investigated the diagnostic performance of single photon emission computed tomography (SPECT)/computed tomography (CT) as a combination of functional and anatomic imaging, in patients with unspecified chest wall pain. Methods Fifty-two patients with unspecified chest wall pain and no history of recent major traumatic events or cardiac disease were included. The number and location of radioactive chest wall lesions were evaluated on both planar images and SPECT/CT. The clinical diagnosis was made based on all of the clinical and imaging data and follow-up information. Results Chest wall diseases were diagnosed in 42 patients (80.8 %). SPECT/CT showed abnormal findings in 35 (67.3 %) patients with positive predictive value (PPV) of 97.1 %. SPECT/CT revealed 56 % more lesions than planar bone scan (P = 0.002) and most of the abnormal radioactive lesions (94.6 %) showed combined morphological changes on the matched CT component. When comparing between age subgroups (< 60 y vs. ≥ 60 y), the prevalence of chest wall disease and diagnosis rate of fracture was significantly higher in the older age group. On SPECT/CT, the older age group showed higher frequency of having abnormal finding (95.8 % vs. 42.9 %, P < 0.001) and significantly more lesions were detected (a total of 189 vs. 32, P = 0.003). Conclusion SPECT/CT showed good diagnostic performance and proved to have higher sensitivity, detecting 56 % more lesions than planar bone scan. A negative result could be helpful for excluding pathologic chest wall disease. SPECT/CT might be recommended for integration in to the diagnostic workup in patients with unspecified chest wall pain, especially in patients ≥ 60 y of age, considering the high disease prevalence and the high frequency of positive results.

Dose estimates of occupational radiation exposure during radioguided surgery of Tc-99m-PSMA-labeled lymph nodes in recurrent prostate cancer

Aim [99mTc]Tc-PSMA-based radioguided surgery (TPRS) represents a curative approach for localized relapse of prostate cancer. For its simplified regulatory permission, the radiation protection authorities require a 99mTc- activity below the exemption limit of 10 MBq at the time of surgery. Our aim was to determine the optimal amount of radioactivity (OAR) to comply with that limit and to estimate the maximum number of TPRS procedures per year and surgeon without triggering the full monitoring obligations. Methods In this retrospective study, a dose rate meter was calibrated using measurements on phantoms and from recently injected (1 min p. i.) patients to determine the activity in the patient from measured dose rates. The effective half-life of 99mTc-PSMA-I&S in patients was determined from repeated dose rate measurements to estimate dose parameters of relevance for radiation protection. External exposures of the surgeons were measured with personal dosimeters calibrated in Hp(10). The surgeon’s finger dose Hp(0.07) is estimated from radioactivity measured in resected lymph nodes. Potenzial incorporations were estimated for an activity of 10 MBq. Results From the first 6 subsequent patients, an effective half-life of 4.15 h was observed. Assuming an operation time 24 h p. i., the OAR was 550 MBq. Operations lasting in average 2 h in a distance of 0.25 m to the patient imply a body dose for surgeons of 4.16 µSv per procedure. Based on these estimates, the surgeon’s Hp(10) is less than 1 mSv per year with up to 241 operations per year. Hp(0.07) and potential incorporation of activity do not lead to further limitations. Summary All radiation protection regulations are met with adherence to OAR recommended here without triggering the full monitoring obligations from radiation protection regulations.