Clinical Study Preliminary Clinical Experience of trans-1-Amino-3-(18)F-fluorocyclobutanecarboxylic Acid (anti-(18)F-FACBC) PET/CT Imaging in Prostate Cancer Patients

Background. In this retrospective analysis we assessed the role of [ 18 F]-FACBC-PET/CT in the prostatic cancer staging. Procedure. first [ 18 F]-FACBC-PET/CT images of 26 patients (68.1 ± 5.8 years) were analyzed. PET/CT findings were compared with PSA concentrations, with PSA doubling times (PDT), and with correlative imaging. Results. On 16 [ 18 F]-FACBC (53.3%) scans, 58 metabolically active lesions were found. 12 (20.7%) lesions corresponding to the local relapse were found in prostate/prostate bed and seminal vesicles, 9 (15.5%) lesions were located in regional lymph nodes, 10 (17.2%) were located in distal lymph nodes, and 26 (44.8%) metabolically active lesions were found in the skeleton. In one case, focal uptake was found in the brain, confirmed further on MRI as meningioma. The mean S-PSA level in patients with positive [ 18 F]-FACBC findings was 9.5 ± 16.9 g/L (0.54-69 g/L) and in patients with negative [ 18 F]-FACBC findings was 1.96 ± 1.87 g/L (0.11-5.9 g/L), but the difference was not statistically significant. However, the PSA doubling time (PDT) in patients with positive findings was significantly shorter than PDT in patients with negative findings: 3.25 ± 2.09 months (0.3-6 months) versus 31.2 ± 22.02 months (8-84 months), < 0.0001. There was a strong positive correlation between PSA value and number of metabolically active lesions ( = 0.74) and a negative correlation between PDT and number of metabolically active lesions ( = −0.56). There was a weak negative correlation between PDT and SUV max ( = −0.30). Conclusion. According to our preliminary clinical experience, [ 18 F]-FACBC-PET may play a role in in vivo restaging of an active prostate cancer, especially in patients with a short S-PSA doubling time

Single Center Experience with a 4-Week 177Lu-PSMA-617 Treatment Interval in Patients with Metastatic Castration-Resistant Prostate Cancer

Background: 177Lu-PSMA-617 is a promising theragnostic treatment for metastatic castration-resistant prostate cancer (mCRPC). However, both the optimal treatment dose and interval in mCRPC and the rate of identification of responders from non-responders among possible treatment candidates are unknown. Methods: 62 men with mCRPC who were treated with 177Lu-PSMA-617 during 1/2017–2/2019 were included in the study. Treatment responses, overall survival (OS) and progression free survival (PFS) were determined. The median follow-up time was 1.4 years (IQR 0.5–2.2). Tumor volume of metastases (MTV), SUVmax and tumor lesion activity (TLA) were quantitated from pre-treatment PSMA PET/CT images together with pre-treatment PSA. Results: An average of three treatment cycles (2–5) were given within a four-week interval. PFS was 4.9 months (2.4–9.6) and OS was 17.2 months (6–26.4). There were no major adverse events reported. A significant PSA response of >50% was found in 58.7% of patients, which was significantly associated with longer OS, p < 0.004. PSA response was not associated with staging PSMA-derived parameters. Conclusions: 177Lu-PSMA-617 treatment in four-week intervals was safe and effective. Almost 60% of patients had a significant PSA response, which was associated with better OS. Pre-treatment PSA kinetics or staging PSMA PET/CT-derived parameters were not helpful in identifying treatment responders from non-responders; better biomarkers are needed to aid in patient selection.© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).fi=vertaisarvioitu|en=peerReviewed

Immunological data from cancer patients treated with Ad5/3-E2F-Delta 24-GMCSF suggests utility for tumor immunotherapy

Oncolytic viruses that selectively replicate in tumor cells can be used for treatment of cancer. Accumulating data suggests that virus induced oncolysis can enhance anti-tumor immunity and break immune tolerance. To capitalize on the immunogenic nature of oncolysis, we generated a quadruple modified oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor (GMCSF). Ad5/3-E2F-Delta 24-GMCSF (CGTG-602) was engineered to contain a tumor specific E2F1 promoter driving an E1 gene deleted at the retinoblastoma protein binding site ("Delta 24"). The fiber features a knob from serotype 3 for enhanced gene delivery to tumor cells. The virus was tested preclinically in vitro and in vivo and then 13 patients with solid tumors refractory to standard therapies were treated. Treatments were well tolerated and frequent tumor-and adenovirus-specific T-cell immune responses were seen. Overall, with regard to tumor marker or radiological responses, signs of antitumor efficacy were seen in 9/12 evaluable patients (75%). The radiological disease control rate with positron emission tomography was 83% while the response rate (including minor responses) was 50%. Tumor biopsies indicated accumulation of immunological cells, especially T-cells, to tumors after treatment. RNA expression analyses of tumors indicated immunological activation and metabolic changes secondary to virus replication.Peer reviewe

Local treatment of a pleural mesothelioma tumor with ONCOS-102 induces a systemic antitumor CD8(+) T-cell response, prominent infiltration of CD8(+) lymphocytes and Th1 type polarization

Peer reviewe

Gene expression analysis of tumors demonstrates an induction of Th1 type immune response following intratumoral administration of ONCOS-102 in refractory solid tumor patients

2014-11-0

Phase I study with ONCOS-102 for the treatment of solid tumors - an evaluation of clinical response and exploratory analyses of immune markers

Peer reviewe

Radium-223-Dichloride in Castration Resistant Metastatic Prostate Cancer—Preliminary Results of the Response Evaluation Using F-18-Fluoride PET/CT

The purpose of this study was to evaluate the outcome after Radium-223-dichloride (223RaCl2) treatment of patients with skeletal metastases of castration resistant prostate cancer using whole-body 18F-Fluoride PET/CT. Sodium 18F-fluoride [18F]-NaF PET/CT was performed prior the treatment of 223RaCl2, after the first cycle and after the sixth cycle. The skeletal metastases were analyzed quantitatively using modified PET response evaluation PERCIST criteria. The patients were also analyzed for S-PSA. All ten patients responded in [18F]-NaF scans after 6 cycles, but interim analysis after the 1st cycle did not give additional information about the outcome. The S-PSA decrease correlated with [18F]-NaF response, only 1 patient demonstrated progressive disease, i.e., &gt;25% increase in S-PSA values during 223RaCl2. Our results (although preliminary) suggest that 18F-Fluoride PET/CT is useful in the follow-up of castration resistant prostate cancer with skeletal metastases

Evaluation of Alpha-Therapy with Radium-223-Dichloride in Castration Resistant Metastatic Prostate Cancer—the Role of Gamma Scintigraphy in Dosimetry and Pharmacokinetics

Radium-223-dichloride (223RaCl2) is a new bone-seeking calcium analogue alpha-emitter, which has obtained marketing authorization for the treatment skeletal metastases of hormone-refractory prostate cancer. The current treatment regimen is based on six consecutive doses of 223RaCl2 at 4 week intervals and the administered activity dose, 50 kBq/kg per cycle is based on patient weight. We analyzed two patients using quantitative serial gamma imaging to estimate dosimetry in tumors and see possible pharmacokinetic differences in the treatment cycles. The lesions were rather well visualized in gamma scintigraphy in spite of low gamma activity (&lt;1.1% gamma radiation) at 0, 7 and 28 days using 30–60 min acquisition times. Both our patients analyzed in serial gamma imagings, had two lesions in the gamma imaging field, the mean counts of the relative intensity varied from 27.8 to 36.5 (patient 1), and from 37.4 to 82.2 (patient 2). The half-lives varied from 1.8 days to 4.5 days during the six cycles (patient 1), and from 1.5 days to 3.6 days (patient 2), respectively. In the lesion half-lives calculated from the imaging the maximum difference between the treatment cycles in the same lesion was 2.0-fold (1.8 vs. 3.6). Of these patients, patient 1 demonstrated a serum PSA response, whereas there was no PSA response in patient 2. From our data, there were maximally up to 4.0-fold differences (62.1 vs. 246.6 ) between the relative absorbed radiation doses between patients as calculated from the quantitative standardized imaging to be delivered in only two lesions, and in the same lesion the maximum difference in the cycles was up to 2.3-fold (107.4 vs. 246.6). Our recommendation based on statistical simulation analysis, is serial measurement at days 0–8 at least 3 times, this improve the accuracy significantly to study the lesion activities, half-lives or calculated relative absorbed radiation doses as calculated from the imaging. Both our patients had originally two metastatic sites in the imaging field; the former patient demonstrated a serum PSA response and the latter demonstrated no PSA response. In these two patients there was no significant difference in the lesion activities, half-lives or calculated relative absorbed radiation doses as calculated from the quantitative imaging. Our results, although preliminary, suggest that dose monitoring can be included as a part of this treatment modality. On the other hand, from the absorbed radiation doses, the response cannot be predicted because with very similar doses, only the former patient responded

Preliminary Clinical Experience of trans-1-Amino-3-(18)F-fluorocyclobutanecarboxylic Acid (anti-(18)F-FACBC) PET/CT Imaging in Prostate Cancer Patients

Background. In this retrospective analysis we assessed the role of [18F]-FACBC-PET/CT in the prostatic cancer staging. Procedure. 30 first [18F]-FACBC-PET/CT images of 26 patients (68.1 ± 5.8 years) were analyzed. PET/CT findings were compared with PSA concentrations, with PSA doubling times (PDT), and with correlative imaging. Results. On 16 [18F]-FACBC (53.3%) scans, 58 metabolically active lesions were found. 12 (20.7%) lesions corresponding to the local relapse were found in prostate/prostate bed and seminal vesicles, 9 (15.5%) lesions were located in regional lymph nodes, 10 (17.2%) were located in distal lymph nodes, and 26 (44.8%) metabolically active lesions were found in the skeleton. In one case, focal uptake was found in the brain, confirmed further on MRI as meningioma. The mean S-PSA level in patients with positive [18F]-FACBC findings was 9.5 ± 16.9 μg/L (0.54–69 μg/L) and in patients with negative [18F]-FACBC findings was 1.96 ± 1.87 μg/L (0.11–5.9 μg/L), but the difference was not statistically significant. However, the PSA doubling time (PDT) in patients with positive findings was significantly shorter than PDT in patients with negative findings: 3.25 ± 2.09 months (0.3–6 months) versus 31.2 ± 22.02 months (8–84 months), P<0.0001. There was a strong positive correlation between PSA value and number of metabolically active lesions (R=0.74) and a negative correlation between PDT and number of metabolically active lesions (R=-0.56). There was a weak negative correlation between PDT and SUVmax⁡ (R=-0.30). Conclusion. According to our preliminary clinical experience, [18F]-FACBC-PET may play a role in in vivo restaging of an active prostate cancer, especially in patients with a short S-PSA doubling time