First experience with whole-body magnetic resonance imaging using MET-RADS-P criteria for interim efficacy evaluation of ²²⁵Ac-PSMA radioligand therapy in metastatic castration-resistant prostate cancer

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BACKGROUND

Radioligand therapy (RLT) with radiopharmaceutical drugs targeting prostate-specific membrane antigen (PSMA) and labeled with therapeutic radionuclides is administered to patients with metastatic castration-resistant prostate cancer (mCRPC) upon neoplasm progression during or after previous systemic drug therapy [1]. The advantage of RLT with ²²⁵Ac-PSMA is the use of α-radiation from actinium-225 (²²⁵Ac), which provides a more potent effect on tumor cells compared to the β-radiation of lutetium-177 (¹⁷⁷Lu) used in the most studied RLT variant with ¹⁷⁷Lu-PSMA [2].

The RECIST 1.1 (Response Evaluation Criteria in Solid Tumours) and PCWG (Prostate Cancer Working Group) criteria, which involve assessing prostate-specific antigen (PSA) levels and tracking changes in skeletal and extra-skeletal lesions, are used to evaluate the therapeutic effect in mCRPC. In this case, it is recommended to examine skeletal lesions using radionuclide methods, and extra-skeletal ones using computed tomography (CT) and magnetic resonance imaging (MRI) [6]. Furthermore, several criteria for evaluating the response to RLT have been proposed based on the results of single-photon emission CT combined with X-ray CT [7], positron emission tomography combined with CT (PET/CT) using PSMA [8], and whole-body MRI (WB-MRI) with METastasis Reporting And Data System for Prostate Cancer (MET-RADS-P) criteria [9]. The latter evaluation system provides information on both skeletal and extra-skeletal neoplasm lesions; however, it has not yet been included in current clinical guidelines, as its effectiveness has not yet been confirmed by a sufficient number of clinical studies. In addition, questions remain unresolved regarding the comparability of results obtained using the MET-RADS-P system with other evaluation approaches, as well as the reliability and reproducibility of the system itself.

AIM

To evaluate the interim effectiveness of ²²⁵Ac-PSMA radioligand therapy using WB-MRI based on MET-RADS-P criteria in patients with metastatic castration-resistant prostate cancer. Additionally, the study sought to analyze the reproducibility of the method (intra-observer agreement) and compare the imaging results with the dynamics of prostate-specific antigen (PSA) levels.

METHODS

Study Design

A pilot prospective cohort study was conducted at a single center. The changes in metastatic lesions were monitored using WB-MRI in patients after a radiotherapy course, with outcomes assessed by the MET-RADS-P system. The consistency of integral response evaluations using MET-RADS-P criteria in relation to changes in PSA concentration was examined. Furthermore, the potential for obtaining supplementary information to clarify the nature of the integral response, based on its progression, was established.

This investigation preceded the execution of the clinical trial protocol for the medicinal product ²²⁵Ac-PSMA-617: "Single-center open-label non-randomized trial: assessment of the safety and therapeutic efficacy of the α-emitting radiopharmaceutical ²²⁵Ac-PSMA-617 during radionuclide therapy of metastatic castration-resistant prostate cancer", permit No. 530 issued to the A. Tsyb Medical Radiological Research Centre (MRRC) — a branch of the National Medical Research Radiological Centre, 07.10.24 by the Ministry of Health of the Russian Federation and aimed at determining the feasibility of using the diagnostic method under study to monitor treatment outcomes.

Our study aimed to assess the changes in metastatic lesions in patients with mCRPC after intravenous administration of ²²⁵Ac-PSMA at doses of 6 to 12 MBq. This was documented during two parallel WB-MRI sessions and PSA blood concentration measurements: before administration and at least one month later. The consistency of MET-RADS-P results for WB-MRI data in both initial and follow-up exams was assessed by having the same radiologist re-evaluate them with a gap of at least 6 months. The study design is illustrated in Fig. 1.

 

Fig. 1. Study design. RLT, radioligand therapy; ²²⁵Ac-PSMA, ²²⁵Ac-prostate-specific membrane antigen; MRI, magnetic resonance imaging; PSA, prostate-specific antigen; RP, radiopharmaceutical; METastasis Reporting and Data System for Prostate Cancer (MET-RADS-P), a system for reporting and classifying metastases in prostate cancer; Prostate Cancer Working Group (PSWG), an international expert group that developed standardized criteria for assessing disease progression and treatment response in metastatic and castration-resistant prostate cancer.

 

Study Setting

Treatment with ²²⁵Ac-PSMA and patient monitoring, including whole-body MRI and PSA testing, were conducted at the MRRC — a branch of the National Medical Research Radiological Centre.

Study Duration

The study was conducted from January 2023 to July 2024. An interim evaluation of RLT effectiveness using MET-RADS-P criteria for WB-MRI results and PCWG criteria for PSA levels 1–2 months after a cycle of ²²⁵Ac-PSMA RLT served as a checkpoint.

Eligibility Criteria

Inclusion criteria:

• Patients with morphologically confirmed prostate cancer, exhibiting castration resistance and distant metastases verified through instrumental and laboratory methods, who meet the selection criteria for RLT with ²²⁵Ac-PSMA.
• The presence in the medical documentation of a signed informed voluntary consent for the use of medical data for scientific purposes.

Non-inclusion criteria:

• General contraindications for MRI (claustrophobia, presence of a pacemaker, etc.);
• Presence of a diagnosed malignant disease at the time of inclusion in the investigation, except for prostate cancer.

Exclusion criteria:

• Termination of patient observation;
• The emergence of pathological conditions included in the list of contraindications for MRI.

Study Outcomes

Main study outcome

The main outcome of the study was the integrated response evaluation based on MET-RADS-P criteria for WB-MRI following one course of RLT with ²²⁵Ac-PSMA, encompassing unidirectional (response/stabilization/progression) and discordant tumor response patterns (with and without progression).

Additional outcome

Additional outcomes encompassed the evaluation of treatment response across specific anatomical regions and metastatic sites, determining intra-expert agreement on MET-RADS-P results, and assessing biochemical response to RLT based on PSA concentration dynamics in line with PCWG eligibility criteria.

Intervention

Whole-body magnetic resonance imaging

WB-MRI was conducted on a 1.5 T MRI scanner (Philips Ingenia, Netherlands) with the patient lying supine, utilizing two body receive coils with a craniocaudal length of 70 cm each, along with a head coil simultaneously.

The scan included contiguous blocks of axial images:

• diffusion-weighted imaging (DWI) from the vertex to the mid-thigh, performed using the Diffusion-Weighted Imaging with Background Suppression (DWIBS) pulse sequence with the following parameters: Time Repetition (TR) — 6520 ms; Time Echo (TE) — 64 ms; Field of View (FOV) — 400 mm; section thickness — 5 mm; number of averages — 4; b-values — 0, 50, 500, 800 s/mm². Apparent diffusion coefficient (ADC) maps were constructed based on these [9];
• T1-weighted images (WI) using the Spin Echo (SE) pulse sequence with the following parameters: TR — 412 ms; TE — 4 ms; FOV — 300 mm; section thickness — 5 mm;
• T2-WI using the Fast Spin Echo (FSE) pulse sequence with the following parameters: TR — 4851 ms; TE — 100 ms; FOV — 400 mm; section thickness — 5 mm.

Additionally, axial/coronal images were obtained using the Short Tau Inversion Recovery (STIR) pulse sequence with the following parameters: TR — 13,761ms; TE — 70 ms; FOV — 400 mm; section thickness — 5 mm. Sagittal images of the vertebrae were obtained using a similar pulse sequence with the following parameters: TR — 2500 ms; TE — 70 ms; FOV — 300 mm; section thickness — 4 mm.

The outcome based on WB-MRI data was evaluated following MET-RADS-P guidelines by comparing baseline and follow-up studies across 13 anatomical regions using the probabilistic Response Assessment Categories (RAC) criterion, where:

• RAC 1 — most likely response to treatment;
• RAC 2 — likely response to treatment;
• RAC 3 — stabilization;
• RAC 4 — likely progression;
• RAC 5 — most likely progression [8, 10].

Furthermore, for each anatomical region, the primary (dominant) RAC category (the most frequent) and the secondary category (the second most frequent) were determined.

Assessment of the patient's integral response to treatment, taking into account all anatomical regions according to the MET-RADS-P system, included both unidirectional (positive/negative) and inconsistent (discordant) responses. Unidirectional changes were characterized by the presence of primary and secondary patterns in all anatomical regions corresponding either only to treatment response (RAC 1–2), only to stabilization (RAC 3), or only to progression (RAC 4–5). A representative magnetic resonance pattern of these response variants is presented in Figs. 2 and 3. An inconsistent response included different results in one or more anatomical regions, for example:

• In one anatomical region, the majority of lesions were categorized as RAC 1–2 (primary pattern), while individual lesions were RAC 3–5 (secondary pattern);
• In one anatomical region, the primary response pattern corresponded to the RAC 1–2 category, and in another region — RAC 3–5.

 

Fig. 2. Representative magnetic resonance imaging of the response to radiation-based therapy. A 64-year-old patient with metastatic castration-resistant prostate cancer with multiple bone lesions. Whole-body magnetic resonance imaging results at the level of the target lesion in the right pelvic bone (red arrows) before the start (a, b, c) and 2 months after one course of radioligand therapy (d, e, f). There are no changes in the lesion on STIR images (a, d) and diffusion-weighted images (b, e); on apparent diffusion coefficient maps (c, f), a signal increase is noted with an increase in its numerical value from 0.67 × 10⁻³ to 1.6 × 10⁻³ mm²/s, which corresponds to the most likely response to treatment (RAC 1). A decrease in prostate-specific antigen concentration from 468 to 51 ng/mL was noted.

 

Fig. 3. Representative magnetic resonance imaging of progression. A 71-year-old patient with metastatic castration-resistant prostate cancer with multiple bone lesions. Whole-body magnetic resonance imaging results before the start (a, c, e) and 1 month after one cycle of radioligand therapy (b, d, f): T1-weighted images at the level of the proximal femur (a, b) and pelvic bones (c, d); maximum intensity projection reconstruction of diffusion-weighted images of the chest. Areas with an increase in the size and number of metastatic foci, along with the emergence of confluent lesions, are marked by red arrows. An increase in prostate-specific antigen concentration from 103 to 212 ng/mL was noted.

 

In the case of a discordant response, the following variants were identified:

• Discordant response without progression (DRWP): RAC 1–2 + RAC 3;
• Discordant response with progression (DRP): RAC 1–3 + RAC 4–5.

Determination of prostate-specific antigen

The examination of blood PSA (total) concentration was performed using a standard technique by chemiluminescent immunoassay of blood serum; the detection limits were 0.008–10100 ng/mL.

PCWG criteria were used to evaluate the response to RLT with ²²⁵Ac-PSMA. Progression was defined as an increase in PSA concentration of 25% or more, as well as an absolute increase of 2 ng/mL or more compared to the nadir. Complete or partial response corresponded to a decrease in PSA concentration of 50% or more and 2 ng/mL or more. Stabilization was defined as a change in PSA concentration ranging from a decrease of less than 50% to an increase of less than 25%, with an absolute change of less than 2 ng/mL [4, 5].

Ethics Approval

The present study was approved by the Ethics Committee of the A. Tsyb Medical Radiological Research Centre — a branch of the National Medical Research Radiological Centre (minutes No. 760 dated 18.01.2023). Signing an informed consent for this investigation was not required, as all patients receiving ²²⁵Ac-PSMA RLT at this center sign a voluntary informed consent for the use of medical data for research purposes. All data used in the study were anonymized.

Statistical Analysis

Descriptive statistics were used to describe and compare the integral assessments of treatment outcomes according to MET-RADS-P criteria for WB-MRI and PCWG criteria for PSA concentration, using the STATISTICA® software package, version 10.0 (StatSoft Inc, USA).

The reproducibility of the MET-RADS-P system results (intra-reader agreement) was assessed using Cohen's kappa coefficient for the primary and secondary patterns in each anatomical region and for the overall evaluation per patient. Consent was interpreted as:

• low (K 0.01–0.20);
• satisfactory (K 0.21–0.40);
• moderate (K 0.41–0.60);
• substantial (K 0.61–0.80);
• excellent/superior (K 0.81–1.00) [11].

The level of significance was set as p < 0.05.

RESULTS

Study Sample Formation

The examination initially included 24 patients who met the eligibility criteria and underwent baseline WB-MRI. Four were later removed from the study for not completing the follow-up WB-MRI.

Examination Characteristics

The patients' prior treatments involved different local and systemic approaches targeting the prostate tumor and metastases, leading to the development of castration resistance in all patients 6–72 months before starting RLT with ²²⁵Ac-PSMA. Detailed information on patients who completed the study is presented in Table 1.

 

Table 1. Clinical data of the patient cohort involved in the study for radioligand therapy with ²²⁵Ac-PSMA

Patients	Prior treatment	Term of clinical recommendations, months	Dose, MBq	Time between first injection and repeated MRI, days	PSA concentration before therapy, ng/mL	PSA concentration after 1 course of therapy, ng/mL1
Patient 1	Hormone therapy; chemotherapy	84	12	30	179	53
Patient 2	Hormone therapy	12	9	34	55	25
Patient 3	Prostatectomy; external beam radiation therapy; chemotherapy; radionuclide therapy (177Lu, 223Ra)	66	9	32	267	134
Patient 4	External beam radiation therapy; hormone therapy; radionuclide therapy (153Sa)	24	6	31	8.7	2.47
Patient 5	Prostatectomy; hormone therapy; chemotherapy	60	12	56	468	51
Patient 6	Hormone therapy; chemotherapy; external beam radiation therapy	12	10	56	642	140
Patient 7	Chemotherapy; hormone therapy; radionuclide therapy (223Ra)	19	12	54	280	180
Patient 8	Hormone therapy; external beam radiation therapy	39	12	57	20.6	5.2
Patient 9	Chemotherapy; hormone therapy	16	12	40	378	185
Patient 10	Chemotherapy; hormone therapy	8	6	60	126	26
Patient 11	Prostatectomy; hormone therapy; orchiectomy; chemotherapy; radionuclide therapy (223Ra)	42	12	57	16.1	5.5
Patient 12	Orchiectomy; hormone therapy; radionuclide therapy (223Ra)	44	6	56	497	277
Patient 13	Hormone therapy	10	9	46	15.1	12.7
Patient 14	Hormone therapy; chemotherapy; radionuclide therapy (223Ra)	40	9	37	778	533
Patient 15	Hormone therapy; chemotherapy	18	9	60	0.18	0.3
Patient 16	Hormone therapy; chemotherapy; radioligand therapy (177Lu)	30	10	27	23.4	24
Patient 17	Hormone therapy; radical prostatectomy; external beam radiation therapy; radioligand therapy (177Lu)	50	10	49	341	324
Patient 18	Hormone therapy; chemotherapy; external beam radiation therapy; radioligand therapy (177Lu)	66	10	48	270	246
Patient 19	Hormone therapy; chemotherapy	10	12	30	77	75
Patient 20	Orchiectomy; hormone therapy; chemotherapy; radioligand therapy (177Lu)	52	12	51	103	212

Note. CR, castration resistance; Ra, radium; Lu, lutetium; Sa, samarium; PSA, prostate-specific antigen; MRI, magnetic resonance imaging; ¹, the timing of the re-evaluation of prostate-specific antigen levels corresponded to the timing of post-therapeutic whole-body magnetic resonance imaging (±3 days).

 

Based on initial WB-MRI data, metastatic spread in 10 of 20 patients (50%) was confined to the skeleton; in the other 10, besides bone lesions, extraskeletal lesions were detected and confirmed by ¹⁸F-PSMA PET/CT; detailed information is available in Table 2. Skeletal involvement was predominantly localized in the pelvic bones, chest wall, and spine. The number of metastatic foci in the femur, humerus, and skull was notably reduced. Enlarged lymph nodes had a predominantly pelvic and retroperitoneal (paraaortic) localization. One patient showed involvement of the mediastinal and hepatic hilar lymph nodes.

 

Table 2. Characteristics of the prevalence of metastatic involvement during primary whole-body magnetic resonance imaging

Patients	Metastatic involvement
	Bone	Lymph nodes	Internal organs
Patient 1	+	+	−
Patient 2	+	−	Kidney
Patient 3	+	+	−
Patient 4	+	−	−
Patient 5	+	−	−
Patient 6	+	−	−
Patient 7	+	−	−
Patient 8	+	−	−
Patient 9	+	+	Adrenal gland, kidney
Patient 10	+	−	−
Patient 11	+	−	−
Patient 12	+	+	−
Patient 13	+	−	−
Patient 14	+	+	Liver
Patient 15	+	−	Testis
Patient 16	+	−	−
Patient 17	+	+	Liver
Patient 18	+	+	Penis
Patient 19	+	−	−
Patient 20	+	+	−

 

Primary Results

Assessment of the integral response to treatment, taking into account all anatomical regions according to the MET-RADS-P system in 20 patients, revealed both a unidirectional (positive/negative) and an inconsistent (discordant) response. We have identified the following groups of treatment outcomes:

• response;
• progression;
• DRWP with a dominant "response" pattern;
• DRWP with a dominant "stabilization" pattern;
• DRP.

The resulting groups were compared with the changes in PSA concentration observed as a result of treatment.

Unidirectional changes in 9 patients (45%) included 7 patients who responded to treatment (RAC 1/2) and one with progression (RAC 5); another patient had a primary stabilization pattern across all anatomical regions. The results of the assessment of follow-up WB-MRI data according to MET-RADS-P criteria after one course of RLT in 20 patients are presented in Table 3.

 

Table 3. Results of post-treatment WB-MRI following MET-RADS-P criteria

Patients	Response assessing categories, primary/secondary1								Response category based on PSA concentration changes2
	C-spine	T-spine	L-spine	Pelvic bones	Chest wall	Extremities	Lymph nodes	Visceral involvement
Patient 1	1	1	1/2	1/2	1/2	1	2	−	Response
Patient 2	2/1	1/3	1/3	1/3	3/1	1/3	−	3	Response
Patient 3	3/2	2/3	2/3	2/3	1/2	3	3	−	Response
Patient 4	−	1	1	1	1	−	−	−	Response
Patient 5	1	1	1	1	1	1	−	−	Response
Patient 6	1	1	1/2	1	1/2	1	−	−	Response
Patient 7	3	1/3	1/3	1/3	3	1/3	−	−	Stabilization
Patient 8	−	−	−	1	−	1	−	−	Response
Patient 9	1	1/2	1	1/2	1/2	1	2	3	Response
Patient 10	1	1	1	1	1	1	−	−	Response
Patient 11	−	−	−	1	−	−	−	−	Response
Patient 12	1	1	1/3	1/2	1/2	1/3	1	−	Stabilization
Patient 13	−	−	−	2/3	1/3	1	-	−	Stabilization
Patient 14	3	2/3	3/2	2/3	2/3	3/2	3	5/2	Stabilization
Patient 15	3	3/2	3	3/2	3	3	−	3	Stabilization
Patient 16	3	2/3	3/2	3	3	3	−	−	Stabilization
Patient 17	3	3/2	3/2	3	3	3	3	5/3	Stabilization
Patient 18	−	−	−	3	4	3	3	3	Stabilization
Patient 19	2/3	3/2	2/3	3/1	3/2	2/3	−	−	Stabilization
Patient 20	5	5	5	5	5	5	5	−	Progression

Note. ¹, Lesions in different response categories (if present) are shown with a slash, with the first and second numbers indicating the primary and secondary patterns, respectively; ², according to PCWG 3 recommendations; C-spine, cervical spine; T-spine, thoracic spine; L-spine, lumbosacral spine; PSA, prostate-specific antigen; METastasis Reporting and Data System for Prostate Cancer (MET-RADS-P), a system for reporting and classifying metastases in prostate cancer.

 

A non-uniform response with varying dynamics was observed in 11 patients (55%), with 8 having DRWP (RAC 1/2 + RAC 3) and 3 having DRP (RAC 1–3 + RAC 4/5). In DRWP, in 6 out of 8 cases, the dominant patterns corresponded to a response (RAC 1/2) to RLT, and in 2 cases, the dominant pattern was RAC 3 (stabilization).

Secondary Results

In the follow-up evaluation after a single course of RLT, the biochemical response based on PCWG criteria was evaluated in 19 patients. For one patient, the initial PSA level was below the minimum recommended for assessing changes (0.18 ng/mL) [5], so his treatment response was not evaluated based on these changes. Based on changes in blood PSA levels, 10 patients responded to RLT with ²²⁵Ac-PSMA, whereas 8 showed stabilization and 1 showed progression.

A comparison of the integral assessments according to MET-RADS-P criteria with the biochemical response is demonstrated in Table 4. In all 8 patients with unidirectional (positive/negative) trends based on MET-RADS-P results, the integral and biochemical response categories matched. The reduction in PSA concentration trends in responding patients ranged from -66 to -89% of the nadir, with a median of -75% (Figs. 4, 5).

 

Table 4. Comparison of the integral response category based on prostate-specific antigen dynamics and according to MET-RADS-P criteria after the first course of radioligand therapy with ²²⁵Ac-PSMA

Response category	Unidirectional positive trend	Unidirectional negative trend	Biochemical response discordance (dominant response)	Biochemical response discordance (dominant stabilization)	DRP
Response	7	−	3	−	−
Stabilization	−	−	3	2	3
Progression	−	1	−	−	−

Note. DRWP, discordant response without progression; DRP, discordant response with progression; MET-RADS-P, reporting and classification system for metastases in prostate cancer.

 

Fig. 4. The results of one cycle of ²²⁵Ac-PSMA radioligand therapy for each patient, assessed by the variation in prostate-specific antigen concentration (as a percentage of nadir) and the overall response type according to MET-RADS-P. Patients marked with arrows showed no progression based on prostate-specific antigen levels at the time of evaluation, but it was later observed in subsequent control studies. PSA, prostate-specific antigen; METastasis Reporting and Data System for Prostate Cancer (MET-RADS-P), a reporting and classification system for metastases in prostate cancer.

 

Fig. 5. Range of changes in prostate-specific antigen concentration (as a percentage of nadir) after one cycle of radioligand therapy for various overall treatment responses according to the MET-RADS-P system. DRWP, discordant response without progression, the dominant pattern is indicated in parentheses; DRP, discordant response with progression; PSA, prostate-specific antigen; METastasis Reporting and Data System for Prostate Cancer (MET-RADS-P), reporting and data system for metastases in prostate cancer; Response Assessment Criteria (RAC), response assessment criteria.

 

The change in PSA concentration in DRWP with a dominant stabilization pattern was insignificant (-2% and +1%), whereas in the dominant RAC 1/2 category, its decrease was -16% … -55% (median — -47%).

Moreover, a difference was observed in the trends of PSA values when comparing groups with a positive unidirectional response and with DRWP (refer to Fig. 4, 5). The small number of observations did not allow for the confirmation of the significance of the identified differences; however, in our view, they deserve attention.

Three patients were observed to have DRP, with two patients having a primary RAC 5 pattern for liver lesions and one in the appendicular skeleton (femur). In all other anatomical regions, tumor "response" or "stabilization" patterns (RAC 1–3) were noted. At this point, all three patients showed a reduction in PSA concentration within the stabilization range (-31, -5, and -9%), which, during further observation 1–3 months later, was followed by an increase of + 20%–30% from the nadir.

Intra-reader agreement using the MET-RADS-P methodology for the primary RAC category was excellent (K 0.88–1.00) for lesions of any location (in the skeleton, lymph nodes, and visceral organs).

According to the verbal assessment scale, intra-reader agreement for the secondary RAC category was substantial for lesions in the chest (K 0.70) and in the limbs (K 0.63). The secondary RAC category was either not present or seldom seen in other anatomical regions (cervical spine, lymph nodes, and visceral lesions), which prevented obtaining significant results for these areas.

Furthermore, according to the verbal assessment scale, intra-reader agreement for the overall assessment (presence/absence of progression per patient) was excellent (K 1.00).

DISCUSSION

Summary of Primary Results

We reported the findings of a pilot single-center prospective study involving a small group of patients, showing that the WB-MRI method with the MET-RADS-P system can detect progression, even in cases of discordant response, in patients with mCRPC treated with one course of RLT using ²²⁵Ac-PSMA.

Discussion of Primary Results

Effective criteria are essential for using RLT in mCRPC treatment to evaluate therapeutic effects, primarily to identify progression and adjust treatment promptly. This fact has led to an active search for new imaging biomarkers of response, including those based on MRI. For instance, in the study C. Parker et al. [12] used quantitative parameters of WB-DWI MRI to evaluate the response to radionuclide therapy with ²²³Ra in 36 patients with mCRPC. They identified a pronounced heterogeneity of response both in individual lesions and in individual patients, including the appearance of new bone metastases in 72% of patients that were absent during the initial examination. The main MRI criterion for evaluating the response of lesions in this study was the change in ADC values.

We used the MET-RADS-P criteria, which include a comprehensive assessment of response on a probability scale based on both anatomical and functional WB-MRI sequences. For certain reasons, this scoring system has not yet become widely used in clinical practice. It provides a notable benefit over other imaging techniques for overseeing systemic treatment of mCRPC by enabling the simultaneous assessment of skeletal and extra-skeletal lesions. The findings of our research enabled a comprehensive evaluation of the response, revealing diverse variants in over half of the patients involved in the study. After one RLT course, progression according to MET-RADS-P criteria was detected in 4 patients (20%), with 3 showing it earlier than indicated by PSA levels. Our data are consistent with the recently published results of a comparative study that evaluated the effectiveness of MET-RADS-P criteria for the formal analysis of WB-MRI. These criteria have been found to detect disease progression sooner than RECIST criteria for extra-skeletal lesions in 4.2% of time points, and sooner than PCWG criteria for bone lesions in 51.9% of time points [13].

As our study showed, a good correlation with biochemical response was observed in the case of a unidirectional result according to MET-RADS-P criteria. A link between the assessment of response based on changes in PSA concentration and the response according to WB-MRI data was also identified in study of C. Parker et al. [12].

The assessment of its reproducibility is of great importance for the clinical application of a diagnostic technique. We evaluated the intra-observer agreement for the MET-RADS-P criteria, which proved to be excellent for the primary RAC pattern in all anatomical regions and for the overall patient response. For the secondary RAC pattern, intra-rater agreement was substantial. According to published data, high reproducibility of the MET-RADS-P criteria and the influence of the radiologist's experience have been noted, especially in the assessment of the secondary RAC pattern, which allows for the identification of a discordant tumor response, which may have clinical relevance for further treatment planning [14, 15].

Study Limitations

Our study has several limitations. Firstly, the small sample size and limited follow-up period did not allow for the determination of the prognostic significance of the results based on overall survival. Secondly, we conducted a comparison only with a biochemical marker of progression and did not compare our results with other imaging markers (CT, conventional radionuclide diagnostic methods, and PSMA PET/CT), which did not allow for their comparative assessment.

CONCLUSION

Based on the findings, we consider WB-MRI with MET-RADS-P criteria a promising tool for assessing RLT effectiveness in mCRPC for both skeletal and extra-skeletal lesions, providing no radiation exposure to the patient and the ability to detect progression earlier than PSA level changes. It is advisable to further study the clinical efficacy of the MET-RADS-P criteria for formal analysis of WB-MRI data, with an assessment of their prognostic significance in ²²⁵Ac-PSMA radioligand therapy.

ADDITIONAL INFORMATION

Author contributions: T.P. Berezovskaia: conceptualization, methodology, data processing, writing — original draft, writing — review & editing; V.O. Ripp: methodology, data curation, formal analysis, writing — original draft; T.Yu. Kochetova, V.V. Krylov: investigation, writing — review & editing; S.A. Ivanov, A.D. Kaprin: data curation, visualization. All the authors approved the version of the manuscript to be published and agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Acknowledgments: The authors express their gratitude to the heads and staff of the clinical departments (the Department of Open-Source Radionuclide Radiosurgery, the Department of Diagnostic Radiology, and the Clinical Laboratory) of the A.F. Tsyb Medical Radiological Research Center for their contribution to the examination and treatment of patients included in the study.

Ethics approval: The study was approved by the Ethics Committee of the A.F. Tsyb Medical Radiological Research Center, a branch of the National Medical Research Center of Radiology (Minutes No. 760, dated January 18, 2023). Written informed consent specific to this study was not required, as all patients receiving radioligand therapy at the A.F. Tsyb Medical Radiological Research Center provide informed consent for the use of their medical data for research purposes. All data used in the study were anonymized.

Consent for publication: Written informed consent was obtained from all patients for the publication of personal data, including photographs, in a scientific journal, at the time of their enrollment in the study. The scope of the published data was approved by the patients.

Funding sources: No funding.

Disclosure of interests: The authors have no relationships, activities, or interests for the last three years related to for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Statement of originality: No previously published material (text, images, or data) was used in this study or article.

Data availability statement: The editorial policy regarding data sharing does not apply to this work.

Generative AI: No generative artificial intelligence technologies were used to prepare this article.

Provenance and peer-review: This article was submitted unsolicited and reviewed following the standard procedure. The peer-review process involved two external reviewers, a member of the Editorial Board, and the in-house science editor.

About the authors

Tatiana P. Berezovskaia

A.F. Tsyb Medical Radiology Centre, National Medical Research Radiological Center

Author for correspondence.
Email: berez@mrrc.obninsk.ru
ORCID iD: 0000-0002-3549-4499
SPIN-code: 5837-3465

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Obninsk

Vladislav O. Ripp

A.F. Tsyb Medical Radiology Centre, National Medical Research Radiological Center

Email: rippnba@gmail.com
ORCID iD: 0000-0001-8970-4212
SPIN-code: 3350-7131
Russian Federation, Obninsk

Tatiana Yu. Kochetova

A.F. Tsyb Medical Radiology Centre, National Medical Research Radiological Center

Email: tat_mail@inbox.ru
ORCID iD: 0000-0002-7809-1059
SPIN-code: 7542-9537
Russian Federation, Obninsk

Valeriy V. Krylov

A.F. Tsyb Medical Radiology Centre, National Medical Research Radiological Center

Email: krylov.mrrc@mail.ru
ORCID iD: 0000-0001-6655-5592
SPIN-code: 2555-1790

MD, Dr. Sci. (Medicine)

Russian Federation, Obninsk

Sergei A. Ivanov

A.F. Tsyb Medical Radiology Centre, National Medical Research Radiological Center; Peoples' Friendship University of Russia

Email: ivanov.obninsk@mail.ru
ORCID iD: 0000-0001-7689-6032
SPIN-code: 4264-5167

MD, Dr. Sci. (Medicine), corresponding member of the Russian Academy of Sciences

Russian Federation, Obninsk; Moscow

Andrei D. Kaprin

Peoples' Friendship University of Russia; P.A. Herzen Moscow Research Institute of Oncology, National Medical Research Radiological Centre; National Medical Research Radiological Center

Email: mnioi@mail.ru
ORCID iD: 0000-0001-8784-8415
SPIN-code: 1759-8101

MD, Dr. Sci. (Medicine), Professor, academician of the Russian Academy of Sciences

Russian Federation, Moscow; Moscow; Obninsk

References

Supplementary files