Points to Consider in the Clinical Development of Radiopharmaceuticals for Positron Emission Tomography Targeting Prostate Specific Membrane Antigen (PSMA PET) — PMDA Early Consideration Summary

In Plain Language

The document addresses clinical development in Japan of radiopharmaceuticals used in positron emission tomography (PET) to target prostate-specific membrane antigen (PSMA), particularly for initial staging and finding prostate cancer that has returned after treatment, as indicated by biochemical evidence. It explains that diagnostic performance is generally evaluated by checking sensitivity and specificity: in everyday terms, how well the imaging identifies disease when it is present and how well it identifies its absence when it is not. For a product approved overseas, on the market for a certain period, and recommended as a major imaging modality in foreign clinical practice guidelines, PMDA says accumulated experience may be considered in establishing that a level of diagnostic performance has been reached. The document also says that foreign clinical trial data may be used as the primary basis for evaluating efficacy and safety in Japanese patients if no clinically significant pharmacokinetic differences between Japanese and non-Japanese populations are identified. It describes criteria under which a product may be considered to have the potential to satisfy requirements for application of the conditional approval system, and discusses image evaluation in a Japanese clinical setting and development as a companion diagnostic.

What This Guidance Covers

The document concerns clinical development of radiopharmaceuticals for PSMA-PET. A radiopharmaceutical is a medicine containing a radioactive component used for imaging; PET detects signals from that component after it has been administered. In this document’s description, the radiopharmaceutical binds to PSMA, which is highly expressed on prostate cancer cells, and imaging detects gamma rays emitted from radiopharmaceuticals taken up into those cells.

The principal intended uses addressed are initial staging of prostate cancer and detection of biochemically recurrent prostate cancer. Initial staging means assessing the extent of cancer as part of the initial evaluation. The document uses “biochemically recurrent” for disease recurrence identified through biochemical evidence; it does not set out a separate definition or threshold for that term in the text provided.

The document’s stated purpose is to outline clinical development considerations that could facilitate introduction into Japanese clinical practice of radiopharmaceuticals for PSMA-PET that are approved in Europe and/or the United States and recommended for those uses. It also addresses the potential use of PSMA-PET to help determine eligibility for specific medicinal products. It does not present a detailed protocol, prescribe a particular sample size or provide specific sensitivity and specificity thresholds in the text.

Why It Matters

The document describes PSMA-PET as having been reported to show superior diagnostic performance for initial staging and detection of biochemically recurrent prostate cancer compared with conventional imaging methods, including computed tomography (CT), magnetic resonance imaging (MRI) and bone scintigraphy. It notes that foreign clinical practice guidelines recommend PSMA-PET as one of the major imaging modalities. The rationale given is that imaging with higher diagnostic performance is expected to contribute to appropriate treatment decisions and, consequently, improved patient prognosis.

Against that background, early adoption of PSMA-PET in Japanese clinical practice had been anticipated, but the document states that, at the time it was written, no radiopharmaceuticals for PSMA-PET intended for initial staging and detection of biochemically recurrent prostate cancer had been approved in Japan. The considerations respond to this setting: they address how overseas experience and evidence might be relevant to Japanese development, while also identifying the need to evaluate image interpretation in a Japanese clinical setting.

Key Recommendations

1. Evaluate diagnostic performance for the intended clinical use. As with other in vivo diagnostic pharmaceuticals, the document says clinical performance should be evaluated by confirming adequate sensitivity and specificity in the intended clinical use. It states that verification of diagnostic performance based on sensitivity and specificity is generally required. The text does not give numerical targets; “adequate” is therefore not translated here into a threshold.

2. Consider the context of overseas approval and accumulated use. The document notes that some PSMA-PET radiopharmaceuticals used for initial staging and detection of biochemically recurrent prostate cancer in Europe and/or the United States have been approved on the basis of exploratory evaluations of sensitivity and specificity. For products approved overseas, used on the market for a certain period, and recommended as a major imaging modality in foreign clinical practice guidelines, PMDA says it may be considered that a certain level of diagnostic performance has been established through accumulated clinical experience in Europe and/or the United States. This is a conditional consideration, not a statement that overseas experience automatically establishes performance for every product or use.

3. Consider foreign trial data for Japanese patients if pharmacokinetic differences are not clinically significant. The document says it may be considered acceptable to evaluate efficacy and safety in Japanese patients primarily on the basis of foreign clinical trial data, provided that no clinically significant differences in pharmacokinetics between Japanese and non-Japanese populations are identified. Pharmacokinetics refers to how a medicine is absorbed, distributed, processed and eliminated in the body. The document gives two reasons for its consideration: PSMA-positive lesions are detected through imaging gamma rays emitted by radiopharmaceuticals taken up into prostate cancer cells by binding to PSMA; and, apart from the availability of PSMA-PET, it describes no substantial differences in the clinical framework for prostate cancer between Japan and other countries.

4. Consider whether the product meets the stated criteria related to conditional approval. The document says radiopharmaceuticals meeting all three criteria below may be considered to have the potential to satisfy the requirements for application of the conditional approval system for pharmaceuticals described in the Director’s Notification:

   • The product has been approved in Europe and/or the United States, has been in use for a certain period since approval, and its standard use in initial staging and detection of biochemically recurrent prostate cancer can be objectively confirmed based on clinical practice guidelines.
   • Based on Phase I study results or equivalent data, it can be confirmed that there are no clear differences in pharmacokinetics between Japanese and non-Japanese populations.
   • Agreement has been reached with PMDA on the clinical trial design intended to verify diagnostic performance.

   The document does not say that meeting these criteria guarantees conditional approval. It describes a potential to satisfy the requirements for application of the system. For consultations about applying the system, sponsors are encouraged to use PMDA’s consultation in accordance with the Director’s Notification.

5. Use Japanese-setting image evaluation and develop interpretation training materials. For products that meet the stated requirements and are subject to the conditional approval system, the document expects clinical experience in Japanese medical practice during development to be limited. It therefore recommends that images obtained in foreign clinical trials be evaluated by image readers within a Japanese clinical setting. Based on those evaluation results, it recommends developing training materials for image interpretation and assessment.

6. Pursue companion diagnostic development in parallel where relevant. The document anticipates that PSMA-PET radiopharmaceuticals may be used not only for initial staging and detection of biochemically recurrent disease but also to support decisions about eligibility for specific medicinal products. Because it may not be straightforward for medical institutions to select among multiple radiopharmaceuticals according to different clinical purposes, the document says it is desirable to pursue development as a companion diagnostic in parallel with development for initial staging and detection of biochemically recurrent prostate cancer.

Practical Implications

Interpretation: Developers planning a Japanese programme can use the document to organise the evidence and questions that need consideration, rather than assuming that overseas approval alone answers them. The intended use matters: the diagnostic performance evidence should relate to the clinical setting for which the product is being developed. The document emphasizes sensitivity and specificity, but does not provide numerical acceptance criteria, so it does not support applying a particular threshold from this summary.

For products with overseas approval and use, teams can document the relevant approval and duration of use, and assess whether clinical practice guidelines objectively support standard use for the intended settings. Separately, Japanese and non-Japanese pharmacokinetics are a consideration for relying primarily on foreign trial data. The conditional-approval criteria refer to “no clear differences” based on Phase I studies or equivalent data, while the broader discussion of relying on foreign trial data is framed as no “clinically significant differences.” These are the document’s respective wordings and should not be treated as interchangeable claims.

The clinical trial design for verifying diagnostic performance is a point for agreement with PMDA under the criteria described. The document encourages sponsors to use PMDA consultation regarding application of the conditional approval system. It does not specify the design elements for that trial, so sponsors and study teams should not infer a particular reference standard, reader design, patient number or analysis method from this summary.

For clinical operations and imaging teams, the recommendation about foreign trial images signals a practical development task when Japanese clinical experience is limited: arrange evaluation by image readers in a Japanese clinical setting, then use those results to develop training materials for image interpretation and assessment. The document does not prescribe the format or content of those materials.

Technical Details

The technical focus is diagnostic performance and the conditions for using clinical evidence. The principal terms and logic are as follows:

The document’s development logic can be read in three linked parts. First, diagnostic performance is generally verified on the basis of sensitivity and specificity. Second, accumulated experience may be relevant for an overseas-approved product used for a certain period and supported for standard use by foreign clinical practice guidelines. Third, foreign efficacy and safety data may form the primary basis for evaluation in Japanese patients when no clinically significant pharmacokinetic differences are identified. These considerations do not remove the document’s stated conditions: the product, intended use, evidence and clinical development plan still need to be considered in context.

The conditional approval discussion adds a specific three-part set of criteria: overseas approval and a certain period of use with objectively confirmed standard use; Phase I results or equivalent data showing no clear pharmacokinetic differences between Japanese and non-Japanese populations; and agreement with PMDA on the clinical trial design to verify diagnostic performance. The document presents these as criteria for considering whether the product may have the potential to satisfy requirements for application of the system, not as an automatic decision rule.

Finally, the image-evaluation recommendation addresses a practical source of uncertainty: limited clinical experience in Japanese medical practice during development for products subject to the conditional approval system. The document recommends evaluation of foreign clinical-trial images by image readers in a Japanese clinical setting, with training materials developed based on the evaluation results. It does not specify an image-reading methodology or a statistical analysis for this evaluation.

Who Should Read It

This document is relevant to sponsors and regulatory affairs teams developing PSMA-PET radiopharmaceuticals for the Japanese market, especially products already approved or used in Europe and/or the United States. It will also be useful to clinical researchers and statisticians planning diagnostic-performance studies; pharmacokinetic specialists assessing Japanese and non-Japanese data; clinical operations teams coordinating image evaluation; and imaging professionals involved in interpretation and reader training. Medical writers and students can use it to understand how the document frames overseas experience, Japanese evidence and potential companion diagnostic development.

Official PMDA Source

• Official title: Points to Consider in the Clinical Development of Radiopharmaceuticals for Positron Emission Tomography Targeting Prostate Specific Membrane Antigen (PSMA PET) (Early Consideration)
• Issuing body: Pharmaceuticals and Medical Devices Agency, Office of New Drug II
• Date on the cover: March 9, 2026
• Official PDF: PMDA document PDF
• PMDA list page: PMDA Early Consideration documents

Source: Pharmaceuticals and Medical Devices Agency (PMDA) website, PMDA Early Consideration documents. This page was created by editing and summarising the PMDA document.

Please consult the official document; this summary does not replace it. PMDA provides the English version for reference, and the Japanese original prevails if the two differ. PMDA describes Early Consideration documents as reference information reflecting the Agency’s views at the time of publication, which may change as scientific knowledge develops.

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