Introduction: The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [¹⁷⁷Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the “617 trial”) to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with ¹⁷⁷Lu-PSMA-617. Materials and methods: The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [¹⁷⁷Lu]Lu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated. Results: The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS. Conclusion: In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [¹⁷⁷Lu]Lu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0–1 is associated with a longer OS.

In recent years, Copper-64 (T1/2 = 12.7 h) in the chemical form of copper dichloride ([64Cu]CuCl2) has been identified as a potential agent for PET imaging and radionuclide therapy targeting the human copper transporter 1, which is overexpressed in a variety of cancer cells. Limited human biodistribution and radiation dosimetry data is available for this tracer. The aim of this research was to determine the biodistribution and estimate the radiation dosimetry of [64Cu]CuCl2, using whole-body (WB) PET scans in healthy volunteers. Six healthy volunteers were included in this study (3 women and 3 men, mean age ± SD, 54.3 ± 8.6 years; mean weight ± SD, 77.2 ± 12.4 kg). After intravenous injection of the tracer (4.0 MBq/kg), three consecutive WB emission scans were acquired at 5, 30, and 60 min after injection. Additional scans were acquired at 5, 9, and 24 h post-injection. Low-dose CT scan without contrast was used for anatomic localization and attenuation correction. OLINDA/EXM software was used to calculate human radiation doses using the reference adult model. The highest uptake was in the liver, followed by lower and upper large intestine walls, and pancreas, in descending order. Urinary excretion was negligible. The critical organ was liver with a mean absorbed dose of 310 ± 67 μGy/MBq for men and 421 ± 56 μGy/MBq for women, while the mean WB effective doses were 51.2 ± 3.0 and 61.8 ± 5.2 μSv/MBq for men and women, respectively. To the best of our knowledge, this is the first report on biodistribution and radiation dosimetry of [64Cu]CuCl2 in healthy volunteers. Measured absorbed doses and effective doses are higher than previously reported doses estimated with biodistribution data from patients with prostate cancer, a difference that could be explained not just due to altered biodistribution in cancer patients compared to healthy volunteers but most likely due to the differences in the analysis technique and assumptions in the dose calculation.

Introduction: Thyroid cancer is the main endocrine neoplasia worldwide, for which ¹³¹I therapy is the cornerstone treatment. One of the main problems of follow up in patients with this type of cancer, is the need for thyroglobulin stimulation, not to mention the poor availability of ¹²³I or ¹²⁴I, to perform studies with a higher degree of sensitivity. Prostatic Specific Membrane Antigen (PSMA) PET/CT has demonstrated to be quite useful in a diversified number of neoplasms, on behalf of its capacity of evaluating the extent of type II carboxypeptidase expression in vascular endothelium. The end point of this article is to assess whether this novel image method possesses applicability in thyroid neoplasms follow up, for diagnostic and potentially therapeutic purposes.Methods: We retrospectively evaluated well differentiated metastatic thyroid cancer patients, who underwent a post therapeutic ¹³¹I dose whole body scan (WBS) and complementary SPECT/CT, as well as ⁶⁸Ga-PSMA–11 PET/CT.Results: Ten patients with differentiated thyroid cancer were included, of whom 80% were women and 20% men, mean age was 58 years old (± 11.6). Sixty-four metastatic lesions were analyzed, 67.19% had papillary histology and 32.81% were follicular type, the most affected site of metastases was bone in 57.81%, followed by lung 17.19%, lymph nodes 7.81%, postoperative thyroid bed 4.69%, brain 4.69% and others 7.81%. ⁶⁸Ga PSMA-11 PET/CT detected 64/64 lesions, all of them also identified by computed tomography (CT), whereas ¹³¹I SPECT/CT detected 55/64 lesions. Discrepant lesions were localized in lung 44.4%, brain 22.2%, postoperative thyroid bed 11.1%, lymph nodes 11.1% and bone 11.1%. The degree of correspondence among observers was outstanding for both radiotracers, but close upon perfect for PSMA-11 (κ = 0.98; 95% CI, 0.80 – 0.91), as opposed to ¹³¹ I (κ = 0.86; 95% CI, 0.71 – 0.76).Conclusions: ⁶⁸Ga-PSMA PET/CT showed an utterly superior capability for metastatic lesion detection when compared to ¹³¹I SPECT/CT. These findings suggest that PSMA PET/CT could possibly and precociously identify radioiodine refractoriness. PSMA uptake values not only expedite diagnosis, but also award it the ability to be used for therapeutic intents.

Fibroblast activation protein (FAP) is highly expressed on the cancer-associated fibroblasts (CAF) of the tumor stroma. Recently, we reported the preclinical evaluation and clinical biokinetics of a novel ^99mTc-labeled FAP inhibitor radioligand ([^99mTc]Tc-iFAP). This research aimed to evaluate [^99mTc]Tc-iFAP for the tumor stroma imaging of six different cancerous entities and analyze them from the perspective of stromal heterogeneity. [^99mTc]Tc-iFAP was prepared from freeze-dried kits with a radiochemical purity of 98 ± 1%. The study included thirty-two patients diagnosed with glioma (n = 5); adrenal cortex neuroendocrine tumor (n = 1); and breast (n = 21), lung (n = 2), colorectal (n = 1) and cervical (n = 3) cancer. Patients with glioma had been evaluated with a previous cranial MRI scan and the rest of the patients had been involved in a [¹⁸F]FDG PET/CT study. All oncological diagnoses were corroborated histopathologically. The patients underwent SPECT/CT brain imaging (glioma) or thoracoabdominal imaging 1 h after [^99mTc]Tc-iFAP administration (i.v., 735 ± 63 MBq). The total lesions (n = 111) were divided into three categories: primary tumors (PT), lymph node metastases (LNm), and distant metastases (Dm). [^99mTc]Tc-iFAP brain imaging was positive in four high-grade WHO III–IV gliomas and negative in one treatment-naive low-grade glioma. Both [^99mTc]Tc-iFAP and [¹⁸F]FDG detected 26 (100%) PT, although the number of positive LNm and Dm was significantly higher with [¹⁸F]FDG [82 (96%)], in comparison to [^99mTc]Tc-iFAP imaging (35 (41%)). Peritoneal carcinomatosis lesions in a patient with recurrent colorectal cancer were only visualized with [^99mTc]Tc-iFAP. In patients with breast cancer, a significant positive correlation was demonstrated among [^99mTc]Tc-iFAP uptake values (Bq/cm³) of PT and the molecular subtype, being higher for subtypes HER2+ and Luminal B HER2-enriched. Four different CAF subpopulations have previously been described for LNm of breast cancer (from CAF-S1 to CAF-S4). The only subpopulation that expresses FAP is CAF-S1, which is preferentially detected in aggressive subtypes (HER2 and triple-negative), confirming that FAP+ is a marker for poor disease prognosis. The results of this pilot clinical research show that [^99mTc]Tc-iFAP SPECT imaging is a promising tool in the prognostic assessment of some solid tumors, particularly breast cancer.