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Purpose: The purpose of this study was to assess whether total-body [68 Ga]Ga-PSMA-11 PET/CT could improve the detection rate compared with conventional [68 Ga]Ga-PSMA-11 PET/CT in patients with biochemical recurrent prostate cancer. Methods: Two hundred biochemical recurrent prostate cancer patients with similar clinicopathological characteristics were included, of whom 100 patients underwent early total-body [68 Ga]Ga-PSMA-11 PET/CT and diuretic-delayed total-body [68 Ga]Ga-PSMA-11 PET/CT, and the other 100 patients received early conventional [68 Ga]Ga-PSMA-11 PET/CT and diuretic-delayed conventional [68 Ga]Ga-PSMA-11 PET/CT. The detection rates of total-body [68 Ga]Ga-PSMA-11 PET/CT and conventional [68 Ga]Ga-PSMA-11 PET/CT were compared using a chi-square test and stratified analysis. The image quality of total-body [68 Ga]Ga-PSMA PET/CT and conventional [68 Ga]Ga-PSMA-11 PET/CT was compared based on subjective scoring and objective parameters. Subjective scoring was conducted from background noise and lesion prominence using a 5-point scale. Objective parameters were evaluated by SUVmax, SUVmean, the standard deviation (SD) of SUV, and the signal-to-noise ratio (SNR) of liver and gluteus maximus. The SUVmax of the recurrent lesions was also measured. Results: The liver SD of the total-body [68 Ga]Ga-PSMA-11 PET/CT was significantly lower than that of conventional [68 Ga]Ga-PSMA-11 PET/CT, the SNR was significantly higher than that of conventional [68 Ga]Ga-PSMA-11 PET/CT, and the subjective evaluation was significantly better than that of conventional [68 Ga]Ga-PSMA-11 PET/CT. The detection rate of total-body [68 Ga]Ga-PSMA PET/CT for biochemical recurrence of prostate cancer was significantly higher than that of conventional [68 Ga]Ga-PSMA-11 PET/CT (91.0% vs. 74.0%, P = 0.003). Total-body [68 Ga]Ga-PSMA-11 PET/CT had better detection efficiency for patients with a Gleason score ≤ 8 or PSA ≤ 2 ng/ml. The advantages of diuretic-delayed total-body [68 Ga]Ga-PSMA-11 PET/CT were more obvious. Conclusion: Total-body [68 Ga]Ga-PSMA-11 PET/CT could significantly improve the detection rate compared with conventional [68 Ga]Ga-PSMA-11 PET/CT in patients with biochemical recurrent prostate cancer. [ABSTRACT FROM AUTHOR]

Background: [68Ga]Ga-FAPI-04 (gallium-68-labeled fibroblast activation protein inhibitor-04) PET/CT has been widely used in diagnosing malignant tumors. Total-body PET/CT has a long axial field of view and provides higher sensitivity compared to traditional PET/CT. However, whether the reduced injected dose of [68Ga]Ga-FAPI-04 could obtain qualified imaging has not been evaluated. Purpose: To explore the effect of half-dose [68Ga]Ga-FAPI-04 on image quality and tumor detectability in oncology patients. Methods: A total of twenty-seven patients with tumors or clinically suspected tumors were included, and all patients were scanned with total-body PET/CT after an injected dose of 0.84–1.14 MBq/kg [68Ga]Ga-FAPI-04. All patients obtained superior image quality with 300 s original acquisition time. Images were reconstructed using 180 s, 120 s, 60 s, 40 s, 30 s, 20 s scanning duration by ordered subset expectation maximization algorithm. The subjective image quality of all patients in each time group was scored using 5-point Likert scale. Mediastinal blood pool, liver, spleen, and muscle were analyzed as background using semi-quantitative parameters maximum standardized uptake values (SUVmax), mean standardized uptake values (SUVmean), standard deviation (SD), and signal to noise ratio (SNR). The lesion detection rate, SUVmax, and tumor-to-background ratio (TBR) were calculated for tumors confirmed by pathology. Results: The subjective image quality score decreased with the shortening of scanning time; however, both 180 s and 120 s images met the diagnostic requirements in terms of overall quality, lesion conspicuity, and image noise. The SUVmax of background increased with the reduction of scanning time, while the SUVmean was relatively stable. With the shortening of scanning time, the SD gradually increased, and the SNR gradually decreased, which was consistent with subjective image quality scores. In 180 s and 120 s images, all 11 primary lesions and 79 metastatic lesions were detected. The SUVmax of tumor focus showed an increasing trend as same as the background. Compared with 300 s, the TBR muscle had no statistical difference in 180 s and 120 s. Conclusions: Half-dose [68Ga]Ga-FAPI-04 in total-body PET/CT imaging can shorten the acquisition time to 120 s with acceptable subjective image quality and 100% tumor detection rate. Total-body PET/CT imaging with a half-dose [68Ga]Ga-FAPI-04 and reduced acquisition time can be used in radiation-sensitive and poor tolerant to prolong horizontal positioning and waiting time populations such as children and gravidas. [ABSTRACT FROM AUTHOR]

Purpose: Rucaparib, an FDA-approved PARP inhibitor, is used as a single agent in maintenance therapy to provide promising treatment efficacy with an acceptable safety profile in various types of BRCA-mutated cancers. However, not all patients receive the same benefit from rucaparib-maintenance therapy. A predictive biomarker to help with patient selection for rucaparib treatment and predict clinical benefit is therefore warranted. With this aim, we developed [18F]rucaparib, an 18F-labelled isotopologue of rucaparib, and employed it as a PARP-targeting agent for cancer imaging with PET. Here, we report the in vitro and in vivo evaluation of [18F]rucaparib in human pancreatic cancer models. Method: We incorporated the positron-emitting 18F isotope into rucaparib, enabling its use as a PET imaging agent. [18F]rucaparib binds to the DNA damage repair enzyme, PARP, allowing direct visualisation and measurement of PARP in cancerous models before and after PARP inhibition or other genotoxic cancer therapies, providing critical information for cancer diagnosis and therapy. Proof-of-concept evaluations were determined in pancreatic cancer models. Results: Uptake of [18F]rucaparib was found to be mainly dependent on PARP1 expression. Induction of DNA damage increased PARP expression, thereby increasing uptake of [18F]rucaparib. In vivo studies revealed relatively fast blood clearance of [18F]rucaparib in PSN1 tumour-bearing mice, with a tumour uptake of 5.5 ± 0.5%ID/g (1 h after i.v. administration). In vitro and in vivo studies showed significant reduction of [18F]rucaparib uptake by addition of different PARP inhibitors, indicating PARP-selective binding. Conclusion: Taken together, we demonstrate the potential of [18F]rucaparib as a non-invasive PARP-targeting imaging agent for pancreatic cancers. [ABSTRACT FROM AUTHOR]

Radioligand therapy (RLT) is an expanding field that has shown great potential in the fight against cancer. Radionuclides that can be carried by selective ligands such as antibodies, peptides, and small molecules targeting cancerous cells have demonstrated a clear improvement in the move towards precision medicine. Poly (ADP-ribose) polymerase (PARP) is a family of enzymes involved in DNA damage repair signalling pathway, with PARP inhibitors olaparib, talazoparib, niraparib, veliparib, and rucaparib having FDA approval for cancer therapy in routine clinical use. Based on our previous work with the radiolabelled PARP inhibitor [18F]rucaparib, we replaced the fluorine-18 moiety, used for PET imaging, with iodine-123, a radionuclide used for SPECT imaging and Auger electron therapy, resulting in 8-[123I]iodo-5-(4-((methylamino)methyl)phenyl)-2,3,4,6-tetrahydro-1H-azepino[5,4,3- cd ]indol-1-one, ([123I] GD1), as a potential radiopharmaceutical for RLT. [123I] GD1 was synthesized via copper-mediated radioiodination from a selected boronic esters precursor. In vitro uptake, retention, blocking, and effects on clonogenic survival with [123I] GD1 treatment were tested in a panel of cancer cell lines. Enzymatic inhibition of PARP by GD1 was also tested in a cell-free system. The biodistribution of [123I] GD1 was investigated by SPECT/CT in mice following intravenous administration. Cell-free enzymatic inhibition and in vitro blocking experiments confirmed a modest ability of GD1 to inhibit PARP-1, IC 50 = 239 nM. In vitro uptake of [123I] GD1 in different cell lines was dose dependent, and radiolabelled compound was retained in cells for >2 h. Significantly reduced clonogenic survival was observed in vitro after exposure of cells for 1 h with as low as 50 kBq of [123I] GD1. The biodistribution of [123I] GD1 was further characterized in vivo showing both renal and hepatobiliary clearance pathways with a biphasic blood clearance. We present the development of a new theragnostic agent based on the rucaparib scaffold and its evaluation in in vitro and in vivo models. The data reported show that [123I] GD1 may have potential to be used as a theragnostic agent. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to evaluate the diagnostic performance and image quality of total-body positron emission tomography/computed tomography (PET/CT) imaging using a half-dose of [68 Ga]Ga-prostate specific membrane antigen ([68 Ga]Ga-PSMA) radiotracer, compared to conventional short axial field-of-view PET/CT imaging using a full dose of [68 Ga]Ga-PSMA. Methods: This retrospective study enrolled 52 patients with biochemical recurrent (BCR) prostate cancer after radical prostatectomy who underwent total-body PET/CT with a half-dose (0.9–1.1 MBq/kg) of [68 Ga]Ga-PSMA. These patients were matched by baseline characteristics to another 52 BCR patients after prostatectomy who underwent conventional PET/CT with a full dose (1.8–2.2 MBq/kg) of [68 Ga]Ga-PSMA. The half-dose group was further divided into 5-min (G5) and 2-min (G2) acquisition subgroups. Image quality was assessed through subjective analysis using a 5-point scale and objective measurements of standard uptake value maximum (SUVmax), standard uptake value mean (SUVmean), background variation (BV) of the liver, blood pool, and parotid glands. Additionally, SUVmax and tumor-to-background ratio (TBR) were calculated for lesions. Results: No significant difference in subjective image quality was found between the G2 and full-dose groups (p > 0.05). PET/CT image quality was significantly higher for the G5 versus G2 (p < 0.001) and full-dose groups (p < 0.001). TBR did not differ between the G2 and full-dose groups (4.23 ± 5.21 vs 4.22 ± 3.97, p = 0.99). Liver BV was significantly lower for G2 versus full-dose groups (0.16 ± 0.03 vs 0.20 ± 0.05, p < 0.001). Conclusions: Total-body PET/CT with a half-dose [68 Ga]Ga-PSMA yields image quality superior or comparable to that of conventional PET/CT. The utilization of total-body [68 Ga]Ga-PSMA PET/CT meets the diagnostic demands of BCR patients, particularly those who exhibit reduced tolerance to prolonged horizontal positioning and scan durations, while simultaneously reducing radiation exposure for the subjects. [ABSTRACT FROM AUTHOR]