Emre Demirci

Evaluation of PSMA PET/CT imaging using a 68Ga-HBED-CC ligand in patients with prostate cancer and the value of early pelvic imaging.

PurposeThe aim of the study was to evaluate the diagnostic value of the prostate-specific membrane antigen (PSMA) ligand 68Ga-HBED-CC (PSMA PET/CT) in patients with prostate cancer and evaluate the value of early imaging of the pelvis. Materials and methodsThe files of 28 patients were retrospectively evaluated. All patients had a histopatological confirmation of prostate cancer. PSMA PET/CT images were obtained at 5 and 60 min after injection from all patients. ResultsIntense pathologic radiotracer uptake was observed in 23 patients (77%) at the site of primary tumour. Lymph node metastases were detected in 10 patients (36%) and bone metastases were detected in seven patients (25%). Bone scan (n=25) results revealed metastatic bone lesions in four patients, equivocal results in nine patients and normal results in 12 patients. PSMA PET/CT confirmed bone metastases in all four patients. Pathologic radiotracer uptake in PSMA PET/CT scans was observed only in one patient among those who had equivocal bone scans. PSMA PET/CT showed additional bone lesions in two patients who had a normal bone scan. When we compared early and late pelvic images we found no difference in the number of lesions detected. The maximum standardized uptake value (SUVmax) for primary tumour, lymph nodes and bone metastases was significantly higher in late images. ConclusionPSMA PET/CT imaging seems to be a valuable imaging modality for evaluation of primary prostate cancer and it seems to have potential for the detection of lymph node and bone metastases. Early images 5 min p.i. can help to better distinguish between urinary bladder (before tracer accumulation occurs) and tumour lesions.

Normal distribution pattern and physiological variants of 68Ga-PSMA-11 PET/CT imaging.

Purpose68Ga-PSMA-11 is a novel PET tracer suggested to be used for imaging of advanced prostate cancer. In this study, we aimed to present a detailed biodistribution of 68Ga-PSMA-11, including physiological and benign variants of prostate-specific membrane antigen (PSMA) imaging. Materials and methodsWe carried out a retrospective analysis of 40 patients who underwent PSMA PET/computed tomography (CT) imaging and who had no evidence of residual or metastatic disease on the scans. In addition, 16 patients who underwent PSMA PET/CT imaging with any indication other than prostate cancer were included in the study to evaluate physiological uptake in the normal prostate gland. The median, minimum–maximum, and mean standardized uptake value (SUV) values were calculated for visceral organs, bone marrow and lymph nodes, and mucosal areas. Any physiological variants or benign lesions with 68Ga-PSMA-11 were also noted. Results68Ga-PSMA-11 uptake was noted in the kidneys, parotid and submandibular glands, duodenum, small intestines, spleen, liver, and lacrimal glands, and mucosal uptake in the nasopharynx, vocal cords, pancreas, stomach, mediastinal blood pool, thyroid gland, adrenal gland, rectum, vertebral bone marrow, and testes. Celiac ganglia showed slight 68Ga-PSMA-11 uptake in 24 of 40 patients without the presence of any other pathologic lymph nodes in abdominal and pelvic areas. Variable uptake of 68Ga-PSMA-11 was observed in calcified choroid plexus, a thyroid nodule, an adrenal nodule, axillary lymph nodes and celiac ganglia, occasional osteophytes, and gallbladder. The patient group with PSMA PET/CT for indications other than prostate cancer (n=16) showed a slight radiotracer uptake in normal prostate gland (SUVmax: 5.5±1.6, range: 3.5–8.3). ConclusionThis study shows normal distribution pattern, range of SUVs, and physiological variants of 68Ga-PSMA-11. In addition, several potential pitfalls were documented to prevent misinterpretations of the scan.

Evaluation and comparison of Ga-68 DOTA-TATE and Ga-68 DOTA-NOC PET/CT imaging in well-differentiated thyroid cancer.

BackgroundSomatostatin receptor (Sstr) scintigraphy with radiolabelled somatostatin analogues has been used extensively for the diagnosis and therapy of Sstr-expressing tumours. It has been shown that well-differentiated thyroid cancer (WDTC) cells have a high expression of Sstr2, Sstr3 and Sstr5. Hence, WDTC cells could be an ideal target for the evaluation of lesion uptake of Ga-68 DOTA-1-NaI3-octreotide (DOTA-NOC), which has a high affinity not only to Sstr2 but also to Sstr3 and Sstr5. The aim of the present study was to evaluate the value of Ga-68 DOTA-NOC as a target for Sstr2-expressing, Sstr3-expressing and Sstr5-expressing tumours in WDTC patients and to compare the results with those of Ga-68 DOTA-TATE in the same patient population. MethodThirteen patients with WDTC were included in our study: nine with papillary thyroid cancer, three with Hurthle cell carcinoma and one with follicular thyroid carcinoma. All patients had elevated serum thyroglobulin levels and negative post-therapeutic I-131 whole-body scans, which were obtained after the last radioiodine treatment. All patients had undergone two consecutive PET imaging studies with Ga-68 DOTA-D-Phe1-Tyr3-octreotate (DOTA-TATE) and Ga-68 DOTA-NOC, respectively. All images were evaluated visually, and maximum standardized uptake values were calculated. ResultsBoth Ga-68 DOTA-TATE and Ga-68 DOTA-NOC PET images gave comparable results. Among the 13 patients, imaging with both Ga-68 DOTA-TATE and Ga-68 DOTA-NOC gave negative results in five (38%) patients and positive results in eight (62%) patients. A total of 45 lesions were identified on Ga-68 DOTA-TATE images and 42 on Ga-68 DOTA-NOC images; three lesions were missed. Lesion uptake was significantly higher on Ga-68 DOTA-TATE images. Maximum standardized uptake values of Ga-68 DOTA-TATE and Ga-68 DOTA-NOC were 12.9±9.1 and 6.3±4.1 (n=54, P<0.001), respectively. ConclusionOur study suggested that Ga-68 DOTA-TATE has a higher lesion uptake even in WDTC patients and may have potential advantage over Ga-68 DOTA-NOC.

The accuracy of 68Ga-PSMA PET/CT in primary lymph node staging in high-risk prostate cancer

PurposeTo assess the diagnostic accuracy of 68Ga-PSMA PET in predicting lymph node (LN) metastases in primary N staging in high-risk and very high-risk nonmetastatic prostate cancer in comparison with morphological imaging.MethodsThis was a multicentre trial of the Society of Urologic Oncology in Turkey in conjunction with the Nuclear Medicine Department of Cerrahpasa School of Medicine, Istanbul University. Patients were accrued from eight centres. Patients with high-risk and very high-risk disease scheduled to undergo surgical treatment with extended LN dissection between July 2014 and October 2015 were included. Either MRI or CT was used for morphological imaging. PSMA PET/CT was performed and evaluated at a single centre. Sensitivity, specificity and accuracy were calculated for the detection of lymphatic metastases by PSMA PET/CT and morphological imaging. Kappa values were calculated to evaluate the correlation between the numbers of LN metastases detected by PSMA PET/CT and by histopathology.ResultsData on 51 eligible patients are presented. The sensitivity, specificity and accuracy of PSMA PET in detecting LN metastases in the primary setting were 53%, 86% and 76%, and increased to 67%, 88% and 81% in the subgroup with of patients with ≥15 LN removed. Kappa values for the correlation between imaging and pathology were 0.41 for PSMA PET and 0.18 for morphological imaging.ConclusionsPSMA PET/CT is superior to morphological imaging for the detection of metastatic LNs in patients with primary prostate cancer. Surgical dissection remains the gold standard for precise lymphatic staging.

The role of PSMA PET/CT imaging in restaging of prostate cancer patients with low prostate-specific antigen levels.

Introduction Prostate-specific membrane antigen (PSMA) is increasingly being recognized as a novel target for the PET imaging of prostate cancer (PCa) and 68Ga-DKFZ-11 (68Ga-PSMA) has been suggested as a novel tracer for detection of PCa relapses and metastases. The aim of this study was to evaluate the diagnostic value of PSMA PET/CT in the diagnosis of recurrent PCa with low prostate-specific antigen (PSA) levels. Patients and methods We carried out a retrospective analysis of patients who underwent PSMA PET/CT from November 2013 to December 2014 in our department. Among these patients, 50 out of 178 who had increasing PSA levels (<5 ng/ml) and did not have known metastasis were included in this study. Results Patients had an average PSA of 1.41 ng/ml. A total of 29 patients (58%) showed at least one positive lesion. PET positivity rates of 31% (n=4), 54% (n=13), and 88% (n=14) were observed in patients with a PSA level of less than 0.2, 0.2–2, and 2–5 ng/ml, respectively. A positive correlation was observed between positivity rate and Gleason scores and blood PSA levels. Verification was performed in 46 patients, with biopsy (n=3) and follow-up, and conventional imaging studies at the time of the PET/CT or during follow-up with a mean period of 10.6±3.3 months and ranged from 3.8 to 16.4 months. According to patient-based analysis of 46 cases, 57% of patients had true positive, 24% of patients had true negative, 2% of patients had false positive, an 18% of patients had false-negative findings. A sensitivity of 76.47% (95% confidence interval: 58.83–89.25%) and a specificity of 91.67% (95% confidence interval: 61.52–99.79%) were found. Conclusion PET/CT with 68Ga-PSMA is a valuable tool for assessing recurrence of PCa with a high sensitivity in patients who have PSA levels between 0.2 and 5 ng/ml. In addition, this study suggests that PSMA PET/CT can be used in patients with very low (<0.2 ng/ml) but increasing PSA levels, which, in many cases, may influence further clinical management.

Comparison of Ga-68 DOTA-TATE and Ga-68 DOTA-LAN PET/CT imaging in the same patient group with neuroendocrine tumours: preliminary results.

Introduction Recent studies have suggested that PET imaging with Ga-68-labelled DOTA-somatostatin analogues such as octreotide and octreotate is useful in diagnosing neuroendocrine tumours (NETs) and has superior value over both computed tomography and planar and SPECT somatostatin receptor scintigraphy. Purpose The aim of the present study was to evaluate the role of Ga-68 DOTA-lanreotide (Ga-68-DOTA-LAN) in patients with somatostatin receptor (sst)-expressing tumours and to compare the results of Ga-68 DOTA-D-Phe1-Tyr3-octreotate (Ga-68-DOTA-TATE) in the same patient population. Materials and methods Twelve patients with NETs who were referred to our department for somatostatin receptor scintigraphy were included in the study. There were four patients with well-differentiated neuroendocrine tumour (WDNET) grade 1, two patients with WDNET grade 2, and three patients with poorly differentiated neuroendocrine carcinoma (PDNEC) grade 3. There was also one patient with medullary thyroid cancer, one patient with meningioma and one patient with MEN-1. All patients underwent two consecutive PET imaging studies with Ga-68-DOTA-TATE and Ga-68 DOTA-LAN. All images were evaluated visually, and maximum standardized uptake value was calculated for quantitative evaluation. Results On visual examination of maximum intensity projection images, GA-68 DOTA-LAN was seen to have high background activity and high bone marrow uptake. Both tracers defined 67 lesions. Ga-68 DOTA-TATE images revealed 63 (94%) clearly defined lesions, missing four lesions. In contrast, Ga-68 DOTA-LAN images defined only 23 (44%) lesions, missing 44 (56%) lesions. Thirty-two bone lesions were detected on Ga-68-DOTA-TATE images. Among them, only 11 (34%) were positive on Ga-68 DOTA-LAN images, whereas 21 (66%) were negative. When we evaluated liver, mediastinum and gastrointestinal tract lesions, Ga-68 DOTA-LAN was seen to be positive for 12 (34%) lesions and negative for 23 (66%) lesions. Conclusion Although the results are preliminary, the image quality obtained by Ga-68-DOTA-TATE seems to be superior to that obtained by Ga-68 DOTA-LAN. With its significantly higher lesion uptake and higher ability to detect lesions, Ga-68-DOTA-TATE seems to be a better radioligand compared with Ga-68-DOTA-LAN for the diagnosis of NETs.

Assessment of early therapy response with 18F-FLT PET in glioblastoma multiforme.

Early therapy response assessment in glioblastoma multiforme remains a challenge. Evaluation by MRI relies on changes in tumor contrast enhancement or size, which are usually not visible at early therapy response assessment times. In addition, MRI may not be reliable for early therapy response assessment if only molecular changes have occurred. PET with F-FLT, a tracer associated with cellular proliferation, has been proposed as a potential method of early therapy response assessment and is an area of active research. We present a case where early response assessment with F-FLT PET was associated with a favorable 1-year follow-up outcome.

Lu-177-PSMA-617 Prostate-Specific Membrane Antigen Inhibitor Therapy in Patients with Castration-Resistant Prostate Cancer: Stability, Bio-distribution and Dosimetry

Objective: 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. Methods: 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. Results: The radiochemical yield of Lu-177-PSMA-617 was >99%. 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 (p<0.05) (0.030±0.008 Gy/GBq). Conclusion: 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.

Preclinical Evaluation of 18F-ML-10 to Determine Timing of Apoptotic Response to Chemotherapy in Solid Tumors:

Purpose: We investigated 2-(5-fluoro-pentyl)-2-methyl-malonic acid (18F-ML-10) positron emission tomography (PET) imaging of apoptosis posttherapy to determine optimal timing for predicting chemotherapy response in a mouse head/neck xenograft cancer model. Procedures: BALB/c nude mice (4-8 weeks old) were implanted with UM-SCC-22B tumors. The treatment group received 2 doses of doxorubicin (10 mg/kg, days 0, 2). Small animal 18F-ML-10 PET/computed tomography was performed before and on days 1, 3, and 7 postchemotherapy. Using regions of interest around tumors, 18F-ML-10 uptake change was measured as %ID/g and uptake relative to liver. Terminal Uridine Nick-End Labeling (TUNEL) immunohistochemistry assay was performed using tumor samples of baseline and on days 1, 3, and 7 posttreatment. Results: Treated mice demonstrated increased 18F-ML-10 uptake compared to baseline and controls, and 10 of 13 mice showed tumor volume decreases. All control mice showed tumor volume increases. Tumor-to-liver (T/L) ratios from the control group mice did not show significant change from baseline (P > .05); however, T/L ratios of the treatment group showed significant 18F-ML-10 uptake differences from baseline compared to days 3 and 7 posttreatment (P < .05), but no significant difference at 1 day posttreatment. Conclusion: 2-(5-Fluoro-pentyl)-2-methyl-malonic acid PET imaging has the potential for early assessment of treatment-induced apoptosis. Timing and image analysis strategies may require optimization, depending on the type of tumor and cancer treatment.

ESTIMATION OF THE ORGAN ABSORBED DOSES AND EFFECTIVE DOSE FROM 68Ga-PSMA-11 PET SCAN†

68Ga-PSMA-11 PET/CT has been proven to have high clinical value for imaging of prostate cancer and rapidly gained popularity. In this study, we aimed to investigate absorbed doses of 68Ga-PSMA-11. Seven patients (mean age = 66.9 ± 6.6 years, range: 57-79 years) were enrolled in the study. Whole body PET images were acquired with multiple time points. MIRD method, NUKFIT and OLINDA/EXM software were used for dosimetry calculations. Kidneys, bladder wall, salivary and lacrimal glands received the highest absorbed dose. Estimated absorbed doses to these organs after injection of 150 MBq 68Ga-PSMA-11 were 37.0, 12.6, 14.4 and 6.3 mSv, respectively. Effective dose from PET scanning with 150 MBq injected 68Ga-PSMA-11 was 2.5 mSv. In conclusion, 68Ga-PSMA-11 has a favorable dosimetry profile similar to the 68Ga labeled octreotide analogs, which are used safely in routine clinical practices for many years. No adverse effects were reported. The kidneys were the dose-limiting organs.