Letter to the Editor Regarding "Biodistribution and Semiquantitative Analysis of ^99mTc HYNIC PSMA 11 in Prostate Cancer Patients: A Retrospective Study"

Dear Editor,

We read with great interest the retrospective study by Tayal et al., which explores the biodistribution and semiquantitative performance of technetium-99 m hydrazinonicotinic acid prostate-specific membrane antigen-11 (99mTcHYNIC-PSMA-11) in patients with prostate cancer using single-photon emission computed tomography/computed tomography (SPECT/CT).^[1] The authors' efforts to evaluate a widely accessible, cost-effective radiotracer for prostate cancer imaging in settings without cyclotron access offer a timely, clinically relevant contribution, particularly for resource-limited nuclear medicine centres. However, several methodological and translational aspects of the study design and interpretation merit further investigation.

The categorisation of disease states into "localised" and "oligometastatic" based solely on imaging findings introduces the potential for circular reasoning in semiquantitative analysis. Without histopathologic correlation or confirmatory follow-up imaging, uptake values in equivocal lesions may artificially influence the apparent lack of statistically significant differences in standardised uptake values (SUVs) between groups.^[2] Clinically, this may mask the true biological divergence in prostate-specific membrane antigen (PSMA) expression across disease spectra, limiting the study's utility for risk stratification or therapy selection.

While this study introduced SUV-based biodistribution as a potential screening tool for eligibility for radioligand therapy, the reported uptake values showed substantial variability (e.g., the urinary activity SUVmax standard deviation exceeded 40). This high dispersion weakens the interpretive strength of mean comparisons and suggests a need for harmonised SUV calibration or kinetic modelling^[3] From a clinical decision-making perspective, reliance on uncorrected SUV data in a high-variance environment could lead to inconsistent patient selection for theragnostic protocols.

The study's statistical analysis framework, using independent samples t-tests for each organ-specific SUV without adjustment for multiple comparisons, increases the risk of Type I and Type II errors.^[4] More robust inferential strategies, such as mixed-effects models accounting for repeated measures within patients or adjustment for inter-individual variability in prostate-specific antigen (PSA) levels, may yield greater insight into the biological distribution and potential predictive value of uptake patterns. Given that the mean PSA level in the cohort was markedly skewed (42.80 ± 64.30 ng/mL), stratification by PSA tiers or correlation analyses would enhance the translational relevance.

Despite these limitations, the authors' work supports the broader paradigm that ^99mTc-labelled PSMA imaging may serve as a viable alternative to positron emission tomography/computed tomography (PET/CT) in appropriate settings. Future research integrating histopathological validation and kinetic modelling may unlock the full potential of this approach for guiding radioligand therapy eligibility and staging decisions in prostate cancer. Clarifying these analytical nuances may refine clinical protocols and enhance the role of ^99mTc-HYNIC-PSMA-11 in low-resource nuclear medicine settings.