Optimization of PET protocol and interrater reliability of 18F-PSMA-11 imaging of prostate cancer

Background Several scan parameters for PET imaging with F-18-PSMA-11 such as dosage, acquisition time and scan duration were evaluated to determine the most appropriate scan protocol, as well as the effect of furosemide administration on lesion visualization. Forty-four patients were randomly assigned to a dosage group (2.0 +/- 0.2 or 4.0 +/- 0.4 MBq/kg F-18-PSMA-11). All patients received a full-body PET/CT 1 h and 3 h after radiotracer injection with a scan duration of 3 min/bed position. For comparison of the scan duration, images were reconstructed for 1.5 and 3 min/bed position. Patients were intravenously administered 0.5 mg/kg furosemide with a maximum dose of 40 mg. To evaluate the furosemide effect, 22 additional patients were recruited and received one full-body PET/CT 1 h after administration of 2.0 +/- 0.2 MBq/kg F-18-PSMA-11 with a scan duration of 3 min/bed position. To this group, no furosemide was administered. Images were scored on image quality using a 7-point scale and each suspicious lesion was described. To assess interrater reliability, two nuclear physicians scored all scans independently and described all observed suspicious lesions. Results The 4 MBq/kg group received for all reconstructed images (60 min p.i., 1.5 and 3 min/bed position and 180 min p.i., 1.5 and 3 min/bed position) the highest median image quality score compared to the 2 MBq/kg group (p values < 0.01). When comparing all reconstructed images, the highest image quality score was given to images at 60 min p.i., 3 min/bed position for both dosage groups (score 5 and 6 for 2 and 4 MBq/kg, respectively). The addition of furosemide administration decreased the interference score with one point (p = 0.01106) and facilitated the evaluation of lesions in proximity to the ureters. The interrater reliability for the comparison of each lesion separately after more than 40 F-18-PSMA-11 scan readings showed an increasing kappa value from 0.78 (95% CI, 0.65-0.92) to 0.94 (95% CI, 0.87-1). Conclusion Although the results indicate an administered activity of 4.0 +/- 0.4 MBq/kg, preference will be given to 2.0 +/- 0.2 MBq/kg due to the small difference in absolute score (max 1 point) and the ALARA principle. For evaluation of lesions in proximity to the ureters, the co-administration of a diuretic can be useful. The increase of the kappa value from 0.78 to 0.94 suggests a learning curve in the interpretation of F-18-PSMA-11 images

Automated radiosynthesis of Al[18F]PSMA-11 for large scale routine use.

Objectives: We report a reproducible automated radiosynthesis for large scale batch production of clinical grade Al[F-18]PSMA-11. Methods: A SynthraFCHOL module was optimized to synthesize Al[F-18]PSMA-11 by Al[F-18]-chelation. Results Al[F-18]PSMA-11 was synthesized within 35 min in a yield of 21 +/- 3% (24.0 +/- 6.0 GBq) and a radiochemical purity > 95%. Batches were stable for 4 h and conform the European Pharmacopeia guidelines. Conclusions: The automated synthesis of Al[F-18]PSMA-11 allows for large scale production and distribution of Al [F-18]PSMA-11

Immunoscintigraphy in axial spondyloarthritis : a new imaging modality for sacroiliac inflammation

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Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice

Recently, a 18F-labeled derivative of the widely used 68Ga-PSMA-11 was developed for PET imaging of prostate cancer. Although 18F-PSMA-11 has already been evaluated in a Phase I and Phase II clinical trial, preclinical evaluation of this radiotracer is important for further understanding its dynamic behavior. Saturation binding experiments were conducted by incubation of LNCaP cells with 18F-PSMA-11 or 68Ga-PSMA-11 for 1 h, followed by determination of the specific and aspecific binding. Mice bearing LNCaP or PC-3 xenografts each received ± 3.7 MBq 18F-PSMA-11 and 68Ga-PSMA-11 followed by dynamic acquisition of 2.5 h as well as ± 15 MBq 18F-FDG followed by static acquisition at 1 h post injection (p.i.). Uptake was evaluated by comparison of uptake parameters (SUVmean, SUVmax, TBRmean and TBRmax). Mice underwent ex vivo biodistribution where 18F-PSMA-11 activity was measures in excretory organs (kidneys, bladder and liver) as well as bone fragments (femur, humerus, sternum and skull) to evaluate bone uptake. The dissociation constant (Kd) of 18F-PSMA-11 and 68Ga-PSMA-11 was 2.95 ± 0.87 nM and 0.49 ± 0.20 nM, respectively. Uptake parameters were significantly higher in LNCaP compared to PC-3 xenografts for both 18F-PSMA-11 and 68Ga-PSMA-11, while no difference was found for 18F-FDG uptake (except for SUVmax). Tumor uptake of 18F-PSMA-11 showed a similar trend over time as 68Ga-PSMA-11, although all uptake parameter curves of the latter were considerably lower. When comparing early (60 min p.i.) to delayed (150 min p.i.) imaging for both radiotracers individually, TBRmean and TBRmax were significantly higher at the later timepoint, as well as the SUVmax of 68Ga-PSMA-11. The highest %ID/g was determined in the kidneys (94.0 ± 13.6%ID/g 1 h p.i.) and the bladder (6.48 ± 2.18%ID/g 1 h p.i.). No significant increase in bone uptake was seen between 1 and 2 h p.i. Both radiotracers showed high affinity for the PSMA receptor. Over time, all uptake parameters were higher for 18F-PSMA-11 compared to 68Ga-PSMA-11. Delayed imaging with the latter may improve tumor visualization, while no additional benefits could be found for late 18F-PSMA-11 imaging. Ex vivo biodistribution demonstrated fast renal clearance of 18F-PSMA-11 as well as no significant increase in bone uptake

Neuroendocrine tumor with diarrhea : not always the usual suspects : a case report of metastatic calcitoninoma with literature review

We describe a case of a 59-year-old man without relevant past medical history, presenting with chronic diarrhea and weight loss. Extensive laboratory analysis, stool cultures and gastro- and ileocolonoscopy could not identify a diagnosis. Abdominal imaging revealed a mass in the uncinate process of the pancreas with mesenteric adenopathies and liver metastases. Fine needle aspiration was compatible with a pancreatic neuroendocrine tumor with low proliferative capacity (Ki-67 <1%). Immunohistochemical staining was positive for calcitonin and serum calcitonin levels were clearly elevated. Surprisingly, (18)FDG PET-CT scan was positive, but no tracer uptake was seen on (68)Gallium-DOTATOC PET-CT scan. Treatment with somatostatin analogues was not successful, but long-term tumor control could be obtained with Everolimus. However, no significant effect was seen on stool frequency despite additional treatment with multiple symptomatic therapies, liver-directed therapy with radio- and chemoembolization and additional external radiotherapy to the primary pancreatic tumor. Ondansetron, eventually, seems to be the only therapy, until now, causing a decrease in stool frequency. Functioning pancreatic calcitoninomas are considered to be a rare disease entity with few literature on optimal (nuclear) imaging and treatment. We discuss molecular insights regarding these aspects that can be of great interest to nuclear medicine physicians, pathologists, endocrinologists and gastroenterologists

Parathyroid adenoma mimicking a malignant lymph node on F-18-choline PET-CT

Prostate carcinoma is the most common cancer in men. After local therapy, disease recurs in many patients. A choline PET/CT is indicated in case of biochemical relapse of prostate carcinoma to determine the site of recurrence (local and/or distant) and to help select the next line of therapy. Choline PET-CT is also known to show an elevated uptake in hyperfunctioning parathyroid adenoma. This case report shows the difficulty to distinguish between both entities if they occur simultaneously in an oncologic patient