Ga-68 PSMA Research Articles

Molecular imaging of bone metastases using tumor-targeted tracers

Bone metastasis is a disastrous manifestation of most malignancies, especially in breast, prostate and lung cancers. Since asymptomatic bone metastases are not uncommon, early detection, precise assessment, and localization of them are very important. Various imaging modalities have been employed in the setting of diagnosis of bone metastasis, from plain radiography and bone scintigraphy to SPECT, SPECT/CT, PET/CT, MRI. However, each modality showed its own limitation providing accurate diagnostic performance. In this regard, various tumor-targeted radiotracers have been introduced for molecular imaging of bone metastases using modern hybrid modalities. In this article we review the strength of different cancer-specific radiopharmaceuticals in the detection of bone metastases. As shown in the literature, among various tumor-targeted tracers, 68Ga DOTA-conjugated-peptides, 68Ga PSMA, 18F DOPA, 18F galacto-RGD integrin, 18F FDG, 11C/18F acetate, 11C/18F choline, 111In octreotide, 123/131I MIBG, 99mTc MIBI, and 201Tl have acceptable capabilities in detecting bone metastases depending on the cancer type. However, different study designs and gold standards among reviewed articles should be taken into consideration.

Initial experience of Ga-68 prostate-specific membrane antigen positron emission tomography/computed tomography imaging in evaluation of biochemical recurrence in prostate cancer patients.

Gallium-68 labeled prostate-specific membrane antigen (Ga-68 PSMA) ligand (HBED-CC) is a novel tracer used for prostate cancer imaging. The aim of the study was to investigate the performance of Ga-68 PSMA positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrence (BCR) after definitive treatment. Scans of 96 consecutive patients were analyzed. Sixty-two patients received external beam radiotherapy, 34 underwent radical prostatectomy (RP), and 20 patients were on androgen deprivation therapy. Patients with prostate-specific antigen (PSA) level ≥>0.2 ng/mL following RP and PSA rise by 2 ng/mL or more above the nadir PSA following RT (Phoenix criteria) was considered as BCR, respectively. All patients underwent contrast-enhanced PET/CT after injection of 67–111 MBq Ga-68 PSMA ligand. Detection rates were correlated with serum PSA level. Detection rate for nodal metastases was compared with CT. Results of the scan were validated by using either biopsy or follow-up imaging or clinical follow-up. Seventy-four (77%) patients showed abnormal finding in Ga-68 PSMA PET/CT. The median serum PSA level of the population was 5.5 ng/ml (range 0.2–123 ng/ml). The median PSA of the positive scans was higher than that of the negative scans (6 vs. 1.7 ng/ml) and was statistically significant (P = 0.001 by Mann–Whitney U-test). In post-RP group, the detection rates were 23%, 50%, and 82% for PSA <1, 1–2, and >2 ng/ml, respectively. For post-RT, the detection was 86%, 85%, and 95% for PSA 2–5, 5.1–10, and >10 ng/ml, respectively. PSMA PET/CT revealed nodal metastases in 52 (54%) patients while CT showed pathological nodes only in 27 (28%) patients. Overall PSMA PET/CT revealed more number of nodes than CT (111 vs. 48 nodal station). PSMA PET/CT showed relapse in prostate/prostatic bed in 26 (27%) patients, nodal metastases in 50 (52%), skeletal metastases in 20 (21%), and other sites in 4 (4%) patients. Ga-68 PSMA PET/CT has high detection rate for localizing the site of recurrence in patients with biochemical failure and is superior to CT scan in the detection of nodal disease.

The use of molecular volumetric parameters for the evaluation of Lu-177 PSMA I&T therapy response and survival.

The primary aim of this study was to evaluate the volumetric therapy response via Ga-68 PSMA I&T PET/CT in patients treated with Lu-177 PSMA I&T therapy. The secondary purpose was to determine the impact of volumetric parameter responses to overall survival. PSMA tumor volumes (PSMA-TV) and tumor lesion PSMA expressions (TL-PSMA) were calculated with a semi-automatic program on Ga-68 PSMA I&T PET/CT images that were obtained before and after Lu-177 PSMA I&T therapies with 19 patients. The median overall survival was compared with PSMA-TV, TL-PSMA, SUVmax, PSA, and alteration in PERCIST criteria. PSMA-TV values were decreased in 12 patients (63%), and TL-PSMA values were decreased in 15 patients (79%) following the therapy. The SUVmax and the PSA values were also decreased in 14 (74%) and 10 (53%) patients, respectively. The complete remission (CR) was observed in two patients (10%). The partial response (PR) and progressive disease were observed in 6 (32%) and 11 (58%) patients, respectively, according to PRECIST criteria. The survival rates were statistically significant in patients with a decrease in PSMA-TV and TL-PSMA values than patients without any decrease (p 0.001, p < 0.001, respectively). However, the survival rates did not differ in responders (PR or CR) and non-responders according to the PERCIST criteria (p 0.232). The survival rates did not also differ in responders and non-responders according to the SUVmax and PSA values (p 0.140, p 0.206, respectively). Molecular and volumetric parameters are beneficial in the assessment of Lu-177 PSMA I&T therapy response. Although the number of patients is small, TL-PSMA response, which includes both the tumor volume and PSMA expression in tumor, may be considered as the most valuable parameter for the evaluation of the therapy response and the prediction of survival rate.

Exceptions to the rule: Novel retrospective analysis of a single-center institution of the PSMA PET/CT modality.

e14625 Exceptions to the Rule: Using Pathology as a Gold Standard to Evaluate the Sensitivity of PSMA PET/CT Modality. Background: The experience with the novel Ga-68 PSMA PET/CT imaging and its limitations are described anecdotally in the literature. Cases of false-positive PSMA PET/CT of various benign and malignant etiologies are described in case reports. False-negative PSMA PET/CT results are significantly less well characterized. Our analysis is based on the UCLA Cancer Center experience with patients who underwent PSMA PET/CT and subsequent biopsy of target lesions. Methods: Of 44 evaluable patients, we found four patients with false negative results based on the 'Gold Standard' of pathologic biopsy. In this context, false negative is defined as PSMA PET/CT negative but proven to be PSMA-expressing adenocarcinoma of the prostate using biopsy of target lesions. Results: In our analysis, we found several stark patterns of these false-negative lesions. The vast majority were pulmonary in origin (75%). Their average size was subcentimeter (0.96 cm). The average Gleason Score at diagnosis was relatively high (8.25), while the initial PSA at diagnosis was relatively modest (4.3). A majority (75%) of these patients received radiation to the prostate. In terms of treatment: a majority were on Androgen-Deprivation Therapy (75%); Abiraterone (50%); had received prostatectomy (100%). The average age at diagnosis was 65. Conclusions: False-negative adenocarcinoma of the prostate that has been-biopsy proven to express PSMA has not been described in the literature. This is the first such instance that we can encountered. The implications of this finding are potentially far-reaching, since the lung remains the second most common site of metastasis in prostate cancer after the bone. The average sub-centimeter size of the target lesions that were biopsied suggests that the density of PSMA receptors may have a role in the detection on Ga-68 PSMA PET/CT and correlate with sensitivity.

Addition of docetaxel or abiraterone to androgen deprivation therapy in metastatic castration-naive prostate cancer in South Asian population.

e16514 Background: Clinical trials have shown that addition of Docetaxel or Abiraterone to androgen deprivation therapy (ADT) achieves superior survival outcome in metastatic castration naive prostate cancer (mCNPC) in predominantly western population. We sought to evaluate treatment outcomes of adding Docetaxel or Abiraterone to ADT in South Asian population. Methods: 90 mCNPC patients who received treatment between January 2015 and June 2018 were prospectively followed. Diagnosis was established by TRUS guided prostate biopsy and staging was done by Ga68 PSMA PET CT scan in all patients. Patients who were unfit for combination therapy received ADT alone. Patients diagnosed before June 2017 &amp; fit to receive chemo-hormonal therapy, received ADT+Docetaxel. Patients diagnosed after June 2017 and fit to receive combination were offered ADT+Docetaxel or ADT+Abiraterone and therapy selected based on patient’s choice. Monthly clinical evaluation and PSA measurement was done. Outcome measures analyzed included PSA decline &gt; 90%, serological complete response (PSA &lt; 0.2 ng/ml) and progression to CRPC. 76 patients with atleast 6 months follow-up were included in outcome analysis. Results: Patients received ADT alone (N = 37) or ADT+Docetaxel (N = 31) or ADT+Abiraterone (N = 22). Median age was 72, 64 &amp; 70 years, median PSA was 88, 95 &amp; 38 ng/ml, Gleason score was ≥8 in 57%, 71% &amp; 77% patients in ADT alone, ADT+Docetaxel &amp; ADT+Abiraterone group, respectively. Bone &amp; visceral metastasis were present in 62% &amp; 24%, 74% &amp; 26%, 68% &amp; 23% patients in ADT alone, ADT+Docetaxel &amp; ADT+Abiraterone group, respectively. Outcome analysis in 76 evaluable patients is shown in Table. Conclusions: ADT+Docetaxel &amp; ADT+Abiraterone achieve deeper serological response and reduced progression to CRPC compared to ADT alone in metastatic castration naive prostate cancer patients with South Asian ethnicity. Longer follow up is required to comment on overall survival and also to determine which combination (ADT+Docetaxel or ADT+Abiraterone) is superior to other, if at all.[Table: see text]

The role of (68Ga)PSMA I&T in biochemical recurrence after radical prostatectomy: detection rate and the correlation between the level of PSA, Gleason score, and the SUVmax.

The aim of the study was to retrospectively evaluate the recurrence detection rate of Gallium-68-prostate-specific membrane antigen [(68Ga)PSMA] imaging and therapy (I&T) positron emission tomography/computed tomography (PET/CT) at different PSA levels, which enables early detection of patients with radical prostatectomy. We also aimed to compare Gleason scores, used drugs (LHRH analogs and antiandrogens), PSA levels with SUVmax values, and detection rates. This retrospective study included 107 patients who underwent radical prostatectomy and who underwent (68Ga)PSMA I&T PET/CT imaging between January 2015 and December 2018 for the early detection of recurrence. The PSA values, Gleason scores, treatments, lesions detected on (68Ga)PSMA I&T, and SUVmax values were recorded for all patients. Patients with a median PSA level of 1.22ng/mL were divided into seven groups according to the PSA values. The lowest lesion detection rate was found to be 7/16 patients (43.8%) when the PSA was < 0.2 ng/ml, and the highest lesion detection rate was found to be 33/33 patients (100%) when the PSA was > 3.5ng/ml. There was a positive correlation between PSA level and ppSUVmax (per patient SUVmax) value of the patients with lesions (p < 0.001 and r = 0.49). As the Gleason score increased, the lesion detection rates also increased and there was a significant correlation between these values (p < 0.001 and r = 0.360). A positive correlation was determined between the Gleason scores and ppSUVmax values in patients with lesions (p = 0.007 and r = 0.302). A statistically significant correlation was found between bicalutamide use and lesion detection on (68Ga)PSMA I&T (p < 0.001). A similar relationship was also determined in patients undergoing maximal androgen blockade (MAB) (p = 0.003). Patients determined with lesions on (68Ga)PSMA I&T and who were administered luteinizing hormone-releasing hormone (LHRH) agonists were found to have statistically significantly higher ppSUVmax values than those who were not administered LHRH agonists (p < 0.001). In binary logistic regression test, when PSA levels and Gleason scores were selected as continuous variables, both PSA levels and Gleason scores were demonstrated as significant covariates (p = 0.006 and p = 0.022) for lesion detection; by contrast, bicalutamide and MAB were not found as significant factors. In the present study, (68Ga)PSMA I&T was found to be quite successful in determining lesions in the biochemical recurrence, which is consistent with the findings of other I&T studies and studies conducted with different PSMA ligands. Thus, it can be considered that the use of (68Ga)PSMA I&T will become increasingly common.

Five-year trends of bone scan and prostate-specific membrane antigen positron emission tomography utilization in prostate cancer: A retrospective review in a private centre.

In the last 5years, there has been a significant focus on the use of positron emission tomography (PET) for primary and secondary staging of prostate cancer. In this study, we aim to describe the trends of use between Gallium-68 prostate-specific membrane antigen ligand (Ga-68 PSMA) PET/computed tomography (PSMA PET/CT) and nuclear medicine bone scan (NMBS) for prostate cancer staging in the first institution in Australia to offer both modalities. We evaluated trends in prostate cancer staging/restaging imaging modalities at our facility between the time period January 2013-April 2018. Imaging logs were filtered to identify NMBS and PSMA PET/CT scans done within the time period for prostate cancer. Sub-analysis was undertaken (i) to investigate the number of patients who were imaged using both modalities, (ii) to compare the age of the patients in the NMBS group and the PSMA PET/CT group and (iii) to compare the use of PSMA PET/CT for pre-treatment staging compared to the detection of recurrence or metastatic disease (secondary staging). A total of 3144 examinations were performed in the time period reviewed, with 546 NMBS and 2598 PSMA PET/CT scans performed. In the 6months after PSMA PET/CT was introduced, there was a 45.7% decrease in the number of NMBS performed and 95.3% decrease across the duration of the study. In the PSMA PET/CT cohort, 1569 examinations were performed for pre-treatment staging and 1029 performed for secondary staging. There was a significant difference in the proportion of PSMA PET/CT conducted for pre-treatment staging compared with secondary staging when comparing the first and final 500 examinations (P<0.05). After the introduction of PSMA PET/CT there was a marked decline in the use of NMBS for prostate cancer staging. This finding is of note as it occurred before there was clinical data or guidelines supporting the use of PSMA PET/CT for prostate cancer imaging.

554 - Could 68Ga-PSMA PET/CT play a role in primary prostate cancer localisation? A single institution comparative analysis of 68Ga PSMA PET/CT, multiparametric MRI and prostate biopsy

554 - Could 68Ga-PSMA PET/CT play a role in primary prostate cancer localisation? A single institution comparative analysis of 68Ga PSMA PET/CT, multiparametric MRI and prostate biopsy

Lu-177 PSMA I&amp;T Therapy for Prostate Cancer; Treatment Response, Treatment Toxicity, and Survival Results

Purpose: This study aims to evaluate the serum PSA response, Ga-68 PSMA PET/CT response, hematological/nephrological toxicity and survival results of patients with castration-resistant metastatic prostate cancer who are receiving Lu-177 PSMA therapy.Methods: The data of 57 patients with a mean age of 68 years who were treated with Lu-177 PSMA I&T were retrospectively reviewed. Secondary toxicity to treatment was determined using the criteria of the Common Toxicity Criteria for Adverse Events v5.0. The Kaplan Meier method was used for survival and progression-free survival analysis.Results: Forty percent of patients’ serum PSA values’ showed >25% regression after the first cycle of treatment. Serum PSA values were stable/regressed in 75% of the patients. While 2/57 patients showed grade 3 anemia, none showed grade 3 leukopenia or thrombocytopenia. One of 57 patient showed transient nephrotoxicity. Hematological and nephrological toxicity were not observed after treatment of eight cycles, and the serum PSA values of the patients were decreased by 97%. The mean survival time was 11.6 months in all patients, and 17.2 months in patients with serum PSA response. Progression-free survival was an average of 9.9 months.Conclusion: Providing a stable or regressed disease via single cycle treatment in 75% of patients with progression despite the treatments improving survival is an indicator of the success of the therapy. The low rate of hematological and nephrological toxicity in patients none of the patients that received eight cycles suggests that the treatment is reliable. Survival was longer in patients with serum PSA response after treatment

Utility of Prostate Specific Membrane Antigen Expression in Pancreatic Lesions to Differentiating Inflammatory and Malignant Masses by Using Ga-68 PSMA PET/CT: Exploring a New Diagnostic Avenue

Utility of Prostate Specific Membrane Antigen Expression in Pancreatic Lesions to Differentiating Inflammatory and Malignant Masses by Using Ga-68 PSMA PET/CT: Exploring a New Diagnostic Avenue

The Emergence of Theranostics in the Philippines: Overcoming Challenges and Bringing Hope.

Medical managements are becoming personalized while diseases are being understood at the molecular level. Nuclear medicine is one of the fields actively contributing to this development. In particular, theranostics, a combinatorial term for therapy and diagnostics, enables accurate imaging and subsequent targeted radionuclide treatment. Due to its high impact in healthcare, many countries have begun to offer Ga-68 PET/CT scans and Lu-177 therapies. The Philippines has followed suit through the initiative of this author and able support of the administration and staff of St. Luke's Medical Center. The Ga-68 DOTATATE and PSMA PET/CT scans became officially available in January 2018 while the first peptide receptor radionuclide therapy for neuroendocrine tumor and first PSMA radioligand therapy for prostate cancer occurred in May and June 2018, respectively. Amidst past, present, and future challenges, theranostics has emerged in the Philippines, offering hope to cancer patients in the country.

Possible Role of Ga-68 PSMA PET/CT in Evaluation of Systemic Treatment Response in Patients with Metastatic Prostate Cancer

Possible Role of Ga-68 PSMA PET/CT in Evaluation of Systemic Treatment Response in Patients with Metastatic Prostate Cancer

The role of molecular imaging (PET-CT) in the diagnostic and treatment pf prostate cancer

Prostate cancer is the most frequent cancer type in men in industrialized countries. In case of biochemical recurrent disease of prostate cancer is molecular imaging with PET-CT or PET-MRI avery promising modality for the detection of local recurrence, lymph node involvement or distant metastasis. Of the so far implemented radiopharmaceuticals the radioactive labeled PSMA ligands (i. e. Ga-68 PSMA) have prevailed. There are also in the meanwhile treatment approaches with PSMA ligands (i. e. Lu-177 PSMA) in case of metastatic disease.

Biopsy-Proven Brain Metastases from Prostate Adenocarcinoma on 68Ga PSMA PET/CT: Case Series and Review of the Literature

Biopsy-Proven Brain Metastases from Prostate Adenocarcinoma on 68Ga PSMA PET/CT: Case Series and Review of the Literature

Imaging modalities in synchronous oligometastatic prostate cancer

PurposeAlong with a number of other malignancies, the term “oligometastatic” prostate cancer has recently emerged. It represents an attempt to define a subtype of cancer with a limited metastatic load that might perform more favorably than a distinctly disseminated disease, or even one that may be managed in a potentially curative way. Since there is currently a knowledge gap of what imaging modalities should be utilized to classify patients as having this type of tumor, we aimed to shed light on the role of conventional and marker-based imaging in the setting of synchronous oligometastatic prostate cancer as well as summarize the available evidence for its clinical application.MethodsA literature search on December 15th 2017 was conducted using the Pubmed database.ResultsFunctional imaging techniques like 68Ga PSMA. 68Ga PSMA PET-CT has currently been shown the best detection rates for the assessment of nodal, bone and visceral metastases, especially for smaller lesions at low PSA levels.ConclusionsFunctional imaging helps detect low-burden disease metastatic patients. However, these imaging modalities are not available in every center and thus clinicians may be prone to prescribe systemic treatment rather than referring patients for cytoreductive treatments. We hope that the ongoing prospective trials will help guide clinicians in making a more personalized management of synchronous metastatic patients.

Could 68-Ga PSMA PET/CT become a new tool in the decision-making strategy of prostate cancer patients with biochemical recurrence of PSA after radical prostatectomy? A preliminary, monocentric series.

To evaluate the impact of gallium68PSMA-11 (HBED-CC)-PET/CT on decision-making strategy of patients with relapsing prostate cancer (PC) presenting a second biochemical relapse after radical prostatectomy (RP) and salvage RT or salvage androgen deprivation therapy (ADT). 40 patients were retrospectively analyzed. All of them had received prostatectomy. Thirteen out of 40 were addressed to gallium68PSMA-11 (HBED-CC)-PET/CT for a biochemical relapse after RP, 14/40 after a salvage RT and 13/40 after salvage or adjuvant ADT. The PSA level ranged between 0.1 and 1.62ng/ml (median value: 0.51ng/ml). We studied the impact on the decision-making process of a multidisciplinary tumor board of additional data obtained from gallium68PSMA-11 (HBED-CC)-PET/CT. Thirty-one out of 40 evaluated patients showed positive findings at gallium68PSMA-11 (HBED-CC)-PET/CT (77.5%). Of them, five were positive in the prostatic bed, nine in the pelvic nodes, twelve in nodes outside the pelvis and eight at bone level. Nine patients presented two different sites of relapse (22.5%). Gallium68PSMA-11 (HBED-CC)-PET/CT data changed the therapeutic approach in 28 patients (70%). Gallium68PSMA-11 (HBED-CC)-PET/CT can be a useful tool in the restaging of post-RP, RT or ADT patients presenting biochemical relapse of PC and it could change the decision-making process in up of 70% of these patients. Prospective, larger series are needed to establish the correct role of this very promising tool in the staging and therapeutic approach of PC patients.

EP-1544: Ga-68 PSMA PET/CT in postoperative Prostate Cancer patients

EP-1544: Ga-68 PSMA PET/CT in postoperative Prostate Cancer patients

EP-1566: Metabolic response assessment using Ga68 PSMA PETCT in HR organ confined Prostate cancer post IGIMRT

EP-1566: Metabolic response assessment using Ga68 PSMA PETCT in HR organ confined Prostate cancer post IGIMRT

Prospective, multinational comparison of magnetic resonance imaging (mp-MRI and WB–MRI) F-18 fluorocholine (FCH) and Ga-68 PSMA in high risk men being considered for salvage radiation treatment for biochemical failure post radical prostatectomy

Prospective, multinational comparison of magnetic resonance imaging (mp-MRI and WB–MRI) F-18 fluorocholine (FCH) and Ga-68 PSMA in high risk men being considered for salvage radiation treatment for biochemical failure post radical prostatectomy

68Ga PSMA-11 PET with CT urography protocol in the initial staging and biochemical relapse of prostate cancer

Background68Ga-labelled prostate specific membrane antigen (PSMA) ligand PET/CT is a promising modality in primary staging (PS) and biochemical relapse (BCR) of prostate cancer (PC). However, pelvic nodes or local recurrences can be difficult to differentiate from radioactive urine. CT urography (CT-U) is an established method, which allows assessment of urological malignancies. The study presents a novel protocol of 68Ga-PSMA-11 PET/CT-U in PS and BCR of PC.MethodsA retrospective review of PSMA PET/CT-U preformed on 57 consecutive patients with prostate cancer. Fifty mL of IV contrast was administered 10 min (range 8–15) before the CT component of a combined PET/CT study, acquired approximately 60 min (range 40–85) after administration of 166 MBq (range 91–246) of 68Ga-PSMA-11. PET and PET/CT-U were reviewed by two nuclear medicine physicians and CT-U by a radiologist. First, PET images were reviewed independently followed by PET/CT-U images. Foci of activity which could not unequivocally be assessed as disease or urinary activity were recorded. PET/CT-U was considered of potential benefit in final interpretation when the equivocal focal activity in PET images corresponded to opacified ureter, bladder, prostate bed, seminal vesicles, or urethra. Student’s T test and Pearson’s correlation coefficient was used for assessment of variables including lymph node size and standardized uptake value.ResultsOverall 50 PSMA PET/CT-U studies were performed for BCR and 7 for PS. Median PSA with BCR and PS were 2.0 ± 11.4 ng/ml (0.06–57.3 ng/ml) and 18 ± 35.3 ng/ml (6.8–100 ng/ml), respectively. The median Gleason-score for both groups was 7 (range 6–10). In BCR group, PSMA PET was reported positive in 36 (72%) patients, CT-U in 11(22%) patients and PET/CT-U in 33 (66%) patients. In PS group, PSMA PET detected the primary site in all seven patients, of which one patient with metastatic nodal disease had negative CT finding. Of 40 equivocal foci (27/57 patients) on PET, 11 foci (10/57 patients, 17.5%) were localized to enhanced urine on PET/CT-U, hence considered of potential benefit in interpretation. Of those, 3 foci (3 patients) were solitary sites of activity on PSMA imaging including two local and one nodal site and 4 foci (3 patients) were in different nodal fields.ConclusionsPET/CT-U protocol is a practical approach and may assist in interpretation of 68Ga-PSMA-11 imaging by delineation of the contrast opacified genitourinary system and matching focal PSMA activity with urinary contrast.