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Background A first-in-human study of [18F]-BF3-Cy3-ACUPA, a small-molecule imaging agent that can be unimolecularly both positron emitting and fluorescent, is conducted to determine its safety, biodistribution, radiation dosimetry, feasibility in tumor detection by preoperative positron emission tomography (PET), as well as its intraoperative fluorescence imaging utility in patients with prostate-specific membrane antigen positive (PSMA+) tumors. Methods Ten patients aged 66 ± 7 years received a 6.5 ± 3.2 mCi intravenous injection of [18F]-BF3-Cy3-ACUPA and underwent PET/computed tomography (CT) imaging. Radiation dosimetry of [18F]-BF3-Cy3-ACUPA, normal organ biodistribution, and tumor uptakes were examined. Two patients were prescheduled for radical prostatectomy (RP) with extended pelvic lymphadenectomy approximately 24 hours following [18F]-BF3-Cy3-ACUPA injection and imaging. Without reinjection, intraoperative fluorescence imaging was performed on freshly excised tissue during RP. Frozen sections of excised tissue during RP were submitted for confirmatory histopathology and multiphoton fluorescence and brightfield microscopy. Results Absorbed doses by organs including the kidneys and salivary glands were similar to 68Ga-PSMA-11 imaging. [18F]-BF3-Cy3-ACUPA physiologic radiotracer accumulation and urinary/biliary excretion closely resembled the distribution of other published PSMA tracers including [18F]-JK-PSMA-7, [18F]-PSMA-1007, [18F]-DCFPyL, and [18F]-DCFBC. 19F-BF3-Cy3-ACUPA was retained in PSMA+ cancer tissues in patients for at least 24 hours, allowing for intraoperative fluorescence assessment of the prostate and of the embedded prostate cancer without contrast reinjection. After 24 hours, the imaging agent mostly decayed or cleared from the blood pool. Preoperative PET and fluorescence imaging findings were confirmed with final histopathology and multiphoton microscopy. Conclusion Our first-in-human results demonstrate that [18F]-BF3-Cy3-ACUPA is safe and feasible in humans. Larger trials with this PET tracer are expected to further define its capabilities and its clinical role in the management of PSMA+ tumors, especially in prostate cancer.

PET imaging with F-18 DOPA (FDOPA) and Ga-68 DOTATATE (TATE) shows the most promising results to detect medullary thyroid cancer (MTC) recurrence. We performed this comparative study to detect the site of recurrent or metastatic disease in MTC patients with elevated serum calcitonin (Ctn) and/or carcinoembryonic antigen (CEA) levels. We studied 46 MTC patients (25 women, 21 men) with elevated Ctn and/or CEA levels during follow-up who had both FDOPA and TATE PET/CT scans for re-staging purposes. FDOPA PET imaging yielded an overall sensitivity of 86.8%, specificity of 100%, PPV of 100%, NPV of 61.5%, and accuracy of 89.1%, while TATE PET scan had the same values as 84.2%, 87.5%, 96.9%, 53.8%, and 84.6%, respectively, and there was no statistically significant difference between the two modalities with the exception of the specificity value that was higher for FDOPA imaging. In a subgroup of patients with overt Ctn or CEA elevation, sensitivity of FDOPA increased significantly, whereas TATE sensitivity did not change. FDOPA PET imaging was significantly superior in detecting liver and regional lymph node (LN) metastases, while TATE PET scan was significantly better in the skeletal metastases. Early FDOPA demonstrated 11 invisible lesions on late FDOPA. Both FDOPA and TATE PET/CT imaging are useful to localize recurrences in MTC patients. While TATE imaging is superior to reveal skeletal disease, FDOPA seems better in liver and regional LN metastases; therefore, the two modalities appear complementary in monitoring MTC patients with elevated serum Ctn and/or CEA levels.

The aim of the study was to estimate the radiation-absorbed doses and to study the in vivo and in vitro stability as well as pharmacokinetic characteristics of lutetium-177 (Lu-177) prostate-specific membrane antigen (PSMA)-617.For this purpose, 7 patients who underwent Lu-177-PSMA therapy were included into the study. The injected Lu-177-PSMA-617 activity ranged from 3.6 to 7.4 GBq with a mean of 5.2±1.8 GBq. The stability of radiotracer in saline was calculated up to 48 h. The stability was also calculated in blood and urine samples. Post-therapeutic dosimetry was performed based on whole body and single photon emission computed tomography/computed tomography (SPECT/CT) scans on dual-headed SPECT/CT system.The radiochemical yield of Lu-177-PSMA-617 was99%. It remained stable in saline up to 48 h. Analyses of the blood and urine samples showed a single radioactivity peak even at 24 hours after injection. Half-life of the distribution and elimination phases were calculated to be 0.16±0.09 and 10.8±2.5 hours, respectively. The mean excretion rate was 56.5±8.8% ranging from 41.5% to 65.4% at 24 h. Highest radiation estimated doses were calculated for parotid glands and kidneys (1.90±1.19 and 0.82±0.25 Gy/GBq respectively). Radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p0.05) (0.030±0.008 Gy/GBq).Lu-177-PSMA-617 is a highly stable compound both in vitro and in vivo. Lu-177-PSMA-617 therapy seems to be a safe method for the treatment of castration-resistant prostate cancer patients. The fractionation regime that enables the longest duration of tumor control and/or survival will have to be developed in further studies.Amaç: Çalışmanın amaçları lutesyum-177 (Lu-177) prostat-spesifik membran antijen (PSMA)-617 tedavisinde absorbe edilen dozları hesaplamak, radyofarmasötiğin in vivo ve in vitro kararlılığını araştırmak ve farmakokinetik özelliklerini değerlendirmektir. Yöntem: Bu amaçla 7 hasta çalışmaya dahil edilmiştir. Hastalara 3,6 ila 7,4 GBq arasında değişen dozlarda ortalama 5,2±1,8 GBq Lu-177-PSMA-617 tedavi amacıyla verildi. Radyofarmasötiğin kararlılığı 48 saat süre ile serum fizyolojik içerisinde bekletilerek hesaplandı. Kararlılık ayrıca kan ve idrar örneklerinden de hesaplandı. Tedavi sonrası radyasyon dozu hesaplaması tüm vücut tek foton emisyon bilgisayarlı tomografi/bilgisayarlı tomografi görüntülerinden yapıldı. Bulgular: Lu-177-PSMA-617’nin radyokimyasal verimliliği%99 olarak bulundu. Serum fizyolojik içerisinde 48 saat bozulmadan kaldı. Kan ve idrar örneklerinde yapılan yüksek performanslı sıvı kromotografisi ölçümlerinde 24 saat sonra bile tek bir zirve verdi. Dağılım ve eliminasyon fazlarının yarılanma zamanları sırasıyla 0,16±0,09 ve 10,8±2,5 saat olarak hesaplandı. Ortalama 24 saat ekskresyon hızı %56,5±8,8 olarak bulundu ve ekskresyon hızı %41,5’den %65,4’e kadar değişim gösterdi. Hesaplanan en yüksek radyasyon dozu parotis bezleri ve böbrekler için bulundu ve sırasıyla 1,90±1,19 and 0,82±0,25 Gy/GBq idi. Kemik iliğine verilen radyasyon dozu böbrekler ve parotis beziyle karşılaştırıldığında istatistiksel olarak çok düşüktü (p0,05) (0,030±0,008 Gy/GBq). Sonuç: Lu-177-PSMA-617 in vivo ve in vitro şartlarda oldukça kararlı bir bileşik olarak gözükmektedir. Lu-177-PSMA-617 tedavisi kastrasyona dirençli prostat kanseri hastalarında kullanılabilecek oldukça güvenli bir radyofarmasötik olarak gözükmektedir. Hastalarda en uzun tümör kontrolü sağlayan fraksiyone tedavi yöntemi ileri çalışmalarla geliştirilmelidir.

Besli, Lebriz Uslu/0000-0003-1868-3957; Akgun, Elife/0000-0001-5625-9749; Karayel, Emre/0000-0001-8114-2315; Kabasakal, Levent/0000-0002-4050-1972; SAGER, MUHAMMET SAIT/0000-0003-2013-5845; Pehlivanoglu, Huseyin/0000-0003-4833-0976; Sonmezoglu, Kerim/0000-0003-1215-5184 WOS:000523561000013 PubMed ID: 31997599 Objective: Our aim was to assess the diagnostic performance of F-18 fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) in detecting hyperfunctioning parathyroid tissue (HPT) in patients with elevated parathyroid hormone levels with negative or inconclusive conventional imaging results and to compare the findings with those obtained using technetium-99m sestamibi (MIBI) scintigraphy and neck ultrasonography (US). Materials and Methods: Images of 105 patients with hyperparathyroidism who underwent FCH PET/CT, dual-phase MIBI parathyroid scintigraphy (median interval: 42 days), and neck US were retrospectively analyzed. The gold standard was histopathological findings for 81 patients who underwent parathyroidectomy and clinical follow-up findings in the remaining 24 patients. Sensitivities, positive predictive values (PPVs), and accuracies were calculated for all imaging modalities. Results: Among the 81 patients who underwent parathyroidectomy, either parathyroid adenoma (n = 64), hyperplasia (n = 9), neoplasia (n = 4), or both parathyroid adenoma and hyperplasia (n = 1) were detected, except 3 patients who did not show HPT. Of the 24 (23%) patients who were followed-up without operation, 22 (92%) showed persistent hyperparathyroidism. FCH PET/CT showed significantly higher sensitivity than MIBI scintigraphy and US in detection of HPT (p < 0.01). Sensitivity, PPV, and accuracy of FCH PET/CT were 94.1% (95/101), 97.9% (95/97), and 92.4% (97/105), respectively. The corresponding values for MIBI scintigraphy and US were 45.1% (46/102), 97.9% (46/47), and 45.7% (48/105) and 44.1% (45/102), 93.8% (45/48), and 42.9% (45/105), respectively. Among the 35 patients showing negative MIBI scintigraphy and neck US findings, 30 (86%) showed positive results on FCH PET/CT. FCH PET/CT could demonstrate ectopic locations of HPT in 11 patients whereas MIBI and US showed positive findings in only 6 and 3 patients, respectively. Conclusion: FCH PET/CT is an effective imaging modality for detection of HPT with the highest sensitivity among the available imaging techniques. Therefore, FCH PET/CT can be recommended especially for patients who show negative or inconclusive results on conventional imaging. Istanbul University Scientific Research Projects (BAP)Istanbul University [24412] This research was supported by Istanbul University Scientific Research Projects (BAP) (Project number: 24412).