Prostate-specific membrane antigen (PSMA)-ligand PET imaging provides unprecedented accuracy for whole-body staging of prostate cancer. As PSMA-ligand PET/CT is increasingly adopted in clinical ...trials and routine practice worldwide, a unified language for image reporting is urgently needed. We propose a molecular imaging TNM system (miTNM, version 1.0) as a standardized reporting framework for PSMA-ligand PET/CT or PET/MRI. miTNM is designed to organize findings in comprehensible categories to promote the exchange of information among physicians and institutions. Additionally, flowcharts integrating findings of PSMA-ligand PET and morphologic imaging have been designed to guide image interpretation. Specific applications, such as assessment of prognosis or impact on management, should be evaluated in future trials. miTNM is a living framework that evolves with clinical experience and scientific data.
Eighteen years ago, the EORTC PET criteria standardized for the first time response assessment by FDG PET. Response assessment by FDG PET has been further developed and refined by PERCIST (PET ...response criteria in solid tumors). This review describes the data underlying these two systems for assessing tumor response on FDG PET/CT. It also summarizes recent clinical studies that have compared EORTC criteria and PERCIST with each other as well as with the anatomically based “response criteria in solid tumors” (RECIST). These studies have shown that response assessment by EORTC criteria and PERCIST leads to very similar response classifications. In contrast, there are significant differences between response assessment by PERCIST and RECIST. Preliminary data also suggest that response assessment by PERCIST is better correlated with patient outcome and may be a better predictor for the effectiveness of new anti-cancer therapies than RECIST. If correct, this could have a significant impact on oncologic drug development. However, confirmation of the better predictive value of response assessment by PERCIST by data from randomized trials is still lacking.
Most anticancer drugs are effective only in subgroups of patients, and our current understanding of tumor biology does not allow us to predict accurately which patient will benefit from a specific ...therapeutic regimen. Various techniques have, therefore, been developed for monitoring tumor response to therapy, but measuring tumor shrinkage on CT represents the current standard. Although response assessment on CT has been refined over many years, fundamental limitations remain. Interobserver variability in tumor size measurements is still high because of difficulties in delineating tumor tissue from secondary changes in the surrounding tissues. Furthermore, CT is inaccurate in differentiating viable tumor from necrotic or fibrotic tissue. Consequently, the degree of response may be underestimated on CT. Conversely, if tumor shrinkage is short lived and followed by rapid tumor regrowth, CT may overestimate the beneficial effects of a treatment. Finally, CT is limited in characterizing responses in tumors that do not change in size during therapy. Because the growth rate of untreated human tumors varies tremendously, an unchanged tumor size after some weeks of therapy may represent a drug effect but may also indicate a slowly growing tumor that was not affected by the applied therapy. Molecular imaging with PET and the glucose analogue (18)F-FDG PET has been shown to improve response assessment in several tumor types. In malignant lymphoma, international criteria for monitoring response to therapy have recently been revised, and the (18)F-FDG signal now plays a central role in defining tumor response. In a variety of solid tumors, single-center studies have indicated that (18)F-FDG PET may provide earlier or more accurate assessment of tumor response than CT, suggesting that (18)F-FDG PET could play a significant role in personalizing the treatment of malignant tumors. However, generally accepted criteria for response assessment in solid tumors are missing, which makes it frequently impossible to compare the results of different studies. International guidelines and criteria for response assessment by (18)F-FDG PET in solid tumors are, therefore, eagerly awaited.
Beta-emitting Lu-177-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a new option for metastatic castration-resistant prostate cancer (mCRPC), but its antitumor effect ...can decrease over time.
To report the safety and activity of alpha-emitting Ac-225-PSMA-617 RLT in mCRPC that has progressed after Lu-177-PSMA.
Twenty-six patients were treated under a compassionate use protocol. The eligibility criteria included previous treatment with abiraterone or enzalutamide, previous taxane-based chemotherapy, progression after Lu-177-PSMA, and positive PSMA-ligand uptake. The median number of previous mCRPC regimens was 6. Ac-225-PSMA-617 was given every 8 wk until progression/intolerable side effects.
Prostate-specific antigen (PSA) decline, PSA progression-free survival (PSA-PFS), clinical progression-free survival (cPFS), overall survival (OS), and toxicity were measured.
Sixty-one cycles of Ac-225-PSMA-617 (median number of cycles 2; median activity 9 MBq) were administered. A PSA decline of ≥50% was achieved in 17/26 patients. The median PSA-PFS, cPFS, and OS periods were 3.5 (95% confidence interval CI 1.8–11.2), 4.1 (95% CI 3–14.8), and 7.7 (95% CI 4.5–12.1) mo, respectively. Liver metastases were associated with shorter PSA-PFS (median 1.9 vs 4.0 mo; p = 0.02), cPFS (median 1.8 vs 5.2 mo; p = 0.001), and OS (median 4.3 vs 10.4 mo; p = 0.01). Hematological grade 3/4 toxicities were anemia (35%), leucopenia (27%), and thrombocytopenia (19%). All patients experienced grade 1/2 xerostomia. Two and six patients stopped due to hematological toxicity and xerostomia, respectively. A limitation is the retrospective design.
Ac-225-PSMA-617 showed measurable antitumor effect after Lu-177-PSMA failure in late-stage mCRPC. Grade 3/4 hematological side effects were observed in up to one-third of patients, and xerostomia led to treatment halt in a relevant number of patients.
Ac-225-labeled prostate-specific membrane antigen (PSMA)-617 therapy showed substantial antitumor effect in late metastatic castration-resistant prostate cancer after Lu-177-PSMA failure. However, dry mouth is a common side effect that caused about a quarter of patients to stop therapy.
Ac-225-labeled prostate-specific membrane antigen (PSMA)-617 therapy showed substantial antitumor effect in late metastatic castration-resistant prostate cancer after Lu-177-PSMA. Grade 3/4 hematological toxicities were observed in up to 35% of patients and xerostomia occurred in all patients, resulting in treatment termination in up to one-quarter of patients. Visceral metastases are associated with a worse outcome.
Tumor cell metabolism imaging Plathow, Christian; Weber, Wolfgang A
The Journal of nuclear medicine (1978)
49 Suppl 2
Journal Article
Recenzirano
Odprti dostop
Molecular imaging of tumor metabolism has gained considerable interest, since preclinical studies have indicated a close relationship between the activation of various oncogenes and alterations of ...cellular metabolism. Furthermore, several clinical trials have shown that metabolic imaging can significantly impact patient management by improving tumor staging, restaging, radiation treatment planning, and monitoring of tumor response to therapy. In this review, we summarize recent data on the molecular mechanisms underlying the increased metabolic activity of cancer cells and discuss imaging techniques for studies of tumor glucose, lipid, and amino acid metabolism.
Our objective was to develop version 1.0 of a novel framework for response evaluation criteria in prostate-specific membrane antigen (PSMA) PET/CT (RECIP) and a composite response classification that ...combines responses by prostate-specific antigen (PSA) measurements and by RECIP 1.0 (PSA + RECIP).
This was an international multicenter, retrospective study. One hundred twenty-four men with metastatic castration-specific prostate cancer (mCRPC) who underwent
Lu-PSMA therapy and received PSMA PET/CT at baseline and at an interim time point of 12 wk were included. Pairs of baseline interim PET/CT scans were interpreted by consensus among 3 masked readers for appearance of new lesions. Tumor lesions were segmented, and total PSMA-positive tumor volume (PSMA-VOL) was obtained. Appearance of new lesions and changes in PSMA-VOL were combined to develop RECIP 1.0, which included classifications of complete response (RECIP-CR: absence of any PSMA-ligand uptake on interim PET/CT), partial response (RECIP-PR: decline ≥ 30% in PSMA-VOL and no appearance of new lesions), progressive disease (RECIP-PD: increase ≥ 20% in PSMA-VOL and appearance of new lesions), and stable disease (RECIP-SD: any condition but RECIP-PR or RECIP-PD). Changes in PSA levels at 12 wk by Prostate Cancer Working Group Criteria 3 were recorded. PSA + RECIP results were defined as response (PSA decline ≥ 50% or RECIP-PR/CR) or progression (PSA increase ≥ 25% or RECIP-PD). The study's primary outcome measure was the prognostic value of RECIP 1.0 for overall survival (OS). The secondary outcome measure was the prognostic accuracy (C-index) of PSA + RECIP versus PSA responses.
Patients with RECIP-PD (
= 39; 8.3 mo) had a shorter OS than patients with stable disease (RECIP-SD) (
= 47; 13.1 mo;
< 0.001) or RECIP-PR (
= 38; 21.7 mo;
< 0.001). In identifying responders and progressors, PSA + RECIP had C-indices superior to those of PSA only: 0.65 versus 0.62 (
= 0.028) and 0.66 versus 0.63 (
= 0.044), respectively.
PSMA PET/CT by RECIP 1.0 is prognostic for OS and can be used as a response biomarker to monitor early efficacy of
Lu-PSMA in men with mCRPC. PSA + RECIP may be used as a novel composite endpoint in mCRPC clinical trial design.
Targeting and inhibiting DNA repair pathways is a powerful strategy of controlling malignant growth. One such strategy includes the inhibition of PARP1, a central element in the intracellular DNA ...damage response. To determine and visualize the expression and intercellular distribution of PARP1 in vivo, and to monitor the pharmacokinetics of PARP1 targeted therapeutics, fluorescent small probes were developed. To date, however, it is unclear how these probes behave in a more realistic clinical setting, where DNA damage has been induced through one or more prior lines of therapy. Here, we use one such imaging agent, PARPi-FL, in tissues both with and without prior DNA damage, and investigate its value as a probe for PARP1 imaging. We show that PARP1 expression in oral cancer is high, and that the uptake of PARPi-FL is selective, irrespective of whether cells were exposed to irradiation or not. We also show that PARPi-FL uptake increases in response to DNA damage, and that this increase is reflected in higher enzyme expression. Our findings provide a framework for measuring exposure of cells to external beam radiation, and could help to elucidate the effects of such treatments non-invasively in mouse models of cancer.
Positron emission tomography (PET) allows noninvasive, quantitative studies of various biologic processes in the tumor tissue. By using PET, investigators can study the pharmacokinetics of anticancer ...drugs, identify various therapeutic targets and monitor the inhibition of these targets during therapy. Furthermore, PET provides various markers to assess tumor response early in the course of therapy. A significant number of studies have now shown that changes in tumor glucose utilization during the first weeks of chemotherapy are significantly correlated with patient outcome. These data suggest that PET may be used as a sensitive test to assess the activity of new cytotoxic agents in phase II studies. Furthermore, early identification of nonresponding tumors provides the opportunity to adjust treatment regimens according to the individual chemosensitivity of the tumor tissue. However, further prospective and randomized validation of PET is still required before PET controlled chemotherapy can be used in clinical practice.
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