Phase II Study of 99mTc‑NTP15‑5 SPECT Imaging for Detection of Hand Joint Pathology in Digital Osteoarthritis and Rheumatoid Arthritis

99mTc-NTP 15-5 will be evaluated for its ability to identify pathological hand joints in patients with digital osteoarthritis and rheumatoid arthritis. The primary objective is to determine the imaging agent’s performance in detecting disease‑related joint involvement, which is essential for enhancing diagnostic precision in clinical practice.

Secondary objectives include:

• Assessing the diagnostic performance of the tracer for differential diagnosis between digital osteoarthritis and rheumatoid arthritis.
• Evaluating imaging performance by joint group and within each pathology.
• Determining the prevalence of joint damage by pathology using scintigraphic and radioclinical methods.
• Quantitatively measuring tracer fixation on hand joints for each disease.
• Assessing inter‑observer reproducibility of visual and quantitative image readings.
• Describing tracer uptake in skeletal joints outside the hands based on visual analysis.
• Evaluating the tolerance of the tracer.

The trial enrolled adult participants of both sexes; specific age limits were defined by internal coding (codes 3 and 4) but were not disclosed. The sponsor did not provide the total number of enrolled subjects. Candidates were identified from clinical populations with a confirmed diagnosis of either rheumatoid arthritis (≤5 years disease duration per ACR/EULAR criteria) or symptomatic digital osteoarthritis (≤5 years disease duration), and were required to have a Karnofsky performance status greater than 70 %. Additional inclusion requirements included health‑insurance coverage, written informed consent, and the ability to attend scheduled visits. Women of child‑bearing potential needed a negative serum pregnancy test within 7 days of the investigational injection. Participants in the osteoarthritis cohort were required to discontinue NSAIDs for at least eight days before study procedures. Exclusion criteria encompassed conditions that would interfere with the assessment of hand joint pathology or the safe administration of the radiotracer. Lifestyle considerations were limited to the NSAID washout and adherence to study visits; no other specific dietary or physical‑activity restrictions were imposed.

The study is a prospective phase II diagnostic performance trial evaluating the ability of 99mTc-NTP15-5 administered by intravenous infusion (15 MBq/kg) to identify pathological hand joints in patients with digital osteoarthritis or rheumatoid arthritis. Participants undergo a screening visit to confirm eligibility criteria (Karnofsky index > 70 %, disease duration < 5 years, pain score > 4/10, appropriate laboratory tests including pregnancy test) and to obtain written informed consent. Eligible subjects receive the radiotracer at the baseline visit, followed by standardized hand scintigraphy and, when indicated, ultrasound assessment; imaging is interpreted by blinded readers. A safety follow‑up visit occurs within one week to capture adverse events according to NCI‑CTCAE v5.0, and an end‑of‑study visit finalizes data collection and confirms the composite radiological‑clinical reference standard. Participant involvement spans approximately two weeks from screening to end‑of‑study. Early termination may occur if a serious adverse event related to the investigational product arises, if eligibility criteria are subsequently violated (e.g., positive pregnancy test), or if the participant withdraws consent. The primary efficacy measure is the diagnostic accuracy of the scintigraphic method for detecting abnormal joints among the fifteen hand joints, assessed against the composite reference standard.

The investigational radiopharmaceutical 99mTc NTP15-5 is supplied as an intravenous infusion containing the active moiety triethyl‑[3‑(1,4,7,10,13‑pentazacyclopentadec‑1‑yl)propyl]azanium chloride. The administered activity is weight‑based at a dose of 15 MBq/kg, delivered through a single intravenous infusion over a period defined by the study protocol.

No additional investigational agents or comparator drugs are employed in this trial. Participants receive only the study radiopharmaceutical; standard clinical care for rheumatoid arthritis or digital osteoarthritis is continued as per local practice but is not part of the study intervention.

Administration is performed under controlled conditions with patient weight recorded prior to dosing to ensure accurate activity calculation. Infusion rates and total administered volume are monitored in real time to verify compliance with the prescribed protocol. Documentation of the infusion start and end times, as well as any adverse events occurring during or immediately after administration, is required for each participant.

Efficacy will be evaluated primarily by the diagnostic accuracy of 99mTc‑NTP15‑5 scintigraphic imaging in identifying abnormal hand joints. Joint assessment will be performed by blinded visual interpretation of scintigrams, yielding a binary classification (pathological vs. physiological uptake). The reference standard will be a composite radiological‑clinical analysis of the same joints.

Secondary efficacy measures include:

• Performance of the imaging modality in distinguishing digital osteoarthritis (DAO) from rheumatoid arthritis (RA) based on uptake patterns, with consensus reading applied when initial interpretations differ.
• Detection rates for specific joint complexes: MCP and IP joints of the 2nd–5th fingers for RA; CMC, IP joints of the 2nd–5th fingers and the complete 1st‑finger complex for DAO.
• Proportion of joints classified as pathological by scintigraphic versus radioclinical methods.
• Quantitative assessment of the radial joint‑diaphysis ratio (99mTc‑NTP15‑5 J/D) obtained through semi‑automatic tracing of joint interfaces on scintigraphic images combined with manually defined spherical regions of interest on the radial diaphyses.
• Inter‑observer reproducibility evaluated using Cohen’s kappa for initial visual readings and the intraclass correlation coefficient (ICC) for quantitative measurements.
• Scoring of non‑hand skeletal joints using a four‑point scale (0–3) consistent with the Phase I protocol.
• Recording of adverse events classified according to NCI‑CTCAE v5.0 occurring within one week after tracer injection.

All imaging assessments will be conducted after intravenous administration of 15 MBq/kg 99mTc‑NTP15‑5. Visual and quantitative analyses will be performed by independent readers, with consensus procedures applied as described. Reproducibility statistics and ratio calculations will be derived from the collected image data. Adverse‑event monitoring will be completed within the first week post‑injection.