Background: A remarkable therapeutic efficacy has been demonstrated with ²²⁵Ac-prostate-specific membrane antigen (PSMA)-617 in heavily pre-treated metastatic castration-resistant prostate cancer (mCRPC) patients. We report our experience with ²²⁵Ac-PSMA-617 therapy in chemotherapy-naïve patients with advanced metastatic prostate carcinoma. Methods: Seventeen patients with advanced prostate cancer were selected for treatment with ²²⁵Ac-PSMA-617 in 2-month intervals, with initial activity of 8 MBq, then de-escalation to 7 MBq, 6 MBq or 4 MBq in cases of good response. In one patient, activity was escalated to 13 MBq in the third cycle. Fourteen patients had three treatment cycles administered, while in three patients treatment was discontinued after two cycles due to good response. Six out of 17 patients received additional treatments after the third cycle. Prostate-specific antigen (PSA) was measured every 4 weeks for PSA response assessment. ⁶⁸Ga-PSMA-PET/CT was used for functional response assessment before each subsequent treatment cycle. Serial full blood count, renal function test, and liver function were obtained to determine treatment-related side effects. Results: Good antitumor activity assessed by serum PSA level and ⁶⁸Ga-PSMA-PET/CT was seen in 16/17 patients. In 14/17 patients, PSA decline ≥90% was seen after treatment, including seven patients with undetectable serum PSA following two (2/7) or three cycles (5/7) cycles of ²²⁵Ac-PSMA-617. Fifteen of 17 patients had a > 50% decline in lesions avidity for tracer on ⁶⁸Ga-PSMA-PET/CT including 11 patients with complete resolution (PET-negative and either stable sclerosis on CT for bone or resolution of lymph node metastases) of all metastatic lesions. Grade 1/2 xerostomia was seen in all patients, and none was severe enough to lead to discontinuation of treatment. One patient had with extensive bone marrow metastases and a background anemia developed a grade 3 anemia while another patient with solitary kidney and pre-treatment grade 3 renal failure developed grade 4 renal toxicity following treatment. The group presented with significant palliation of bone pain and reduced toxicity to salivary glands due to de-escalation. Conclusions: ²²⁵Ac-PSMA-617 RLT of chemotherapy-naïve patients with advanced metastatic prostate carcinoma led to a ≥ 90% decline in serum PSA in 82% of patients including 41% of patients with undetectable serum PSA who remained in remission 12 months after therapy. The remarkable therapeutic efficacy reported in this study could be achieved with reduced toxicity to salivary glands due to de-escalation of administered activities in subsequent treatment cycles. This necessitates further exploration for informing clinical practice and clinical trial design.

Background: Metastatic prostate carcinoma over-expresses the prostate specific membrane antigen (PSMA) making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience in a series of 73 castrate resistant prostate carcinoma patients treated with ²²⁵Ac-PSMA-617, identifying variables predictive for overall and progression free survival following ²²⁵Ac-PSMA-617 treatment. Methods: ²²⁵Ac-PSMA-617 was administered to patients with mCRPC who had exhausted available therapy options for their disease. Full blood count, glomerular filtration rate and liver function test were obtained at baseline and on follow-up for evaluation of toxicity. ⁶⁸Ga-PSMA PET/CT was obtained at baseline, prior to every treatment cycle and on follow-up for patients’ selection for treatment, to determine the activity of treatment agent to be adminsitered and for response assessment. Serial (prostate specific antigen) PSA was obatianed for PSA response assessment. Results: Seventy-three men (mean age=69 years, range:45-85) with mCRPC were treated with 210 cycles of ²²⁵Ac-PSMA-617. In 70% of patients, a PSA decline of ≥50% was obtained while 83% of patients had any PSA decline. In 29% of patients, all lesions on ⁶⁸Ga-PSMA-PET resolved in response to treatment. During follow-up, 23 patients experienced disease progression while 13 patients died from their disease. The estimated median progression free survival (PFS) and overall survival (OS) were 15.2 months (95% CI: 13.1 – 17.4) and 18 months (95% CI: 16.2 – 19.9) respectively. On univariate analyses factors such as baseline PSA, any PSA decline, PSA decline ≥50%, prior chemotherapy, prior radiation therapy, baseline hemoglobin level were associated with longer PFS and OS (all p 50% proved significantly associated with OS and PFS in multivariate analysis following treatment with ²²⁵Ac-PSMA-617. Furthermore, previous ¹⁷⁷Lu-PSMA treatment was negatively associated with PFS in both uni- and multivariate analysis.

Introduction: The introduction of ¹⁸F-labelled prostate-specific membrane antigen (PSMA) targeted positron emission tomography/computed-tomography (PET/CT) tracers, firstly ¹⁸F-DCFPyL and more recently ¹⁸F-PSMA-1007, have demonstrated promising results for the diagnostic workup of prostate cancer (PCa). This clinical study presents an intra-individual comparison to evaluate tracer-specific characteristics of ¹⁸F-DCFPyL versus ¹⁸F-PSMA-1007. Methods: Twelve prostate cancer patients, drug naive or prior to surgery, received similar activities of about 250 MBq ¹⁸F-DCFPyL and ¹⁸F-PSMA-1007 48 h apart and were imaged 2 h p.i. in the same PET/CT-scanner using the same reconstruction-algorithm. Normal organ biodistribution and tumor uptakes were quantified using SUV_max. Results: PSMA-positive lesions were detected in twelve out of twelve PCa patients. Both tracers, ¹⁸F-DCFPyL and ¹⁸F-PSMA-1007, detected the identical lesions. No statistical significance could be observed when comparing the SUV_max of ¹⁸F-DCFPyL and ¹⁸F-PSMA-1007 for local tumor, lymph node metastases and bone metastases. With regard to normal organs, ¹⁸F-DCFPyL presented statistically significant higher uptake in kidneys, urinary bladder and lacrimal gland. Vice versa, significantly higher uptake of ¹⁸F-PSMA-1007 in muscle, submandibular and sublingual gland, spleen, pancreas, liver and gallbladder was observed. Conclusion: Excellent imaging quality was achieved with both ¹⁸F-DCFPyL and ¹⁸F-PSMA-1007 resulting in identical clinical findings for the evaluated routine situations. Non-urinary excretion of ¹⁸F-PSMA-1007 might present some advantage with regard to delineation of local recurrence or pelvic lymph-node metastasis in selective patients; the lower hepatic background might favor ¹⁸F-DCFPyL in very late stages when rare cases of liver metastases can occur.

Introduction Inflammation forms an important core of the aetiopathogenic process involved in many diseases affecting the heart and the blood vessels. These diseases include infections as well as inflammatory non-infectious cardiovascular conditions. The common feature of this is invasion of the heart or blood vessel by inflammatory cells. F-18 2-fluoro 2-deoxy-D glucose (FDG) is an analogue of glucose and like glucose it is taken up by activated inflammatory cells that accumulate at the site of infection. This has formed the basis of the use of F-18 FDG PET/CT in the non-invasive evaluation of human inflammatory diseases. Sources of data This review is based on the published academic articles as well as our clinical experience. Areas of agreement F-18 FDG PET/CT is a useful imaging modality in the evaluation of cardiovascular inflammatory disorders. Accumulation and distribution of F-18 FDG at the site of inflammation/infection corresponds to severity of the inflammation/infection and extent of involvement. Areas of controversy Most studies evaluating utility of F-18 FDG PET/CT in imaging cardiovascular inflammation are small observational studies hence are potentially prone to bias. Growing points Being a hybrid metabolic and morphologic imaging technique, F-18 FDG PET/CT offers combined advantage of complementary anatomic and metabolic information in disease process. This makes it a useful modality in the diagnosis, determination of extent of disease, prognostication as well as treatment monitoring. Areas timely for developing research Larger prospective studies are needed to validate the superiority of F-18 FDG PET/CT imaging over conventional anatomic imaging modalities.