RadiolabeledNanoparticleQualityChecker

Radiolabeled Nanoparticle

decay correction endotoxins heavy metals impurities PET radionuclide purity radiopharma SPECT

Radiolabeled Nanoparticle Quality Checker — Universal QC for radiolabeled nanocarriers

ℹ️ Utility checks quality of radiolabeled nanoparticles (liposomes, LNPs, polymer NPs) for research use:
• Radionuclide quality: specific activity, radiochemical purity, free radionuclide, parent impurity
• Nanoparticle characteristics: particle size, polydispersity index (PDI), zeta potential
• Safety parameters: pH, endotoxins, sterility, heavy metals
• Adaptive limits based on radionuclide type and target organ

⚠️ IMPORTANT: INVESTIGATIONAL USE ONLY
Radiolabeled nanoparticles are NOT approved by FDA/EMA for clinical use.
All human/animal studies require ethics committee approval.
Parameters are RESEARCH-GRADE estimates and must be validated per study protocol.

Usage:
RadiolabeledNanoparticleQualityChecker.exe → demo mode (console output)
RadiolabeledNanoparticleQualityChecker.exe input.csv output.json → evaluate your data

Input format (CSV):
BatchNumber,Radionuclide,NanoparticleType,TargetOrgan,SpecificActivityMBqPerUmol,RadiochemicalPurityPercent,FreeRadionuclidePercent,ParentNuclideImpurityPercent,ParticleSizeNm,PolydispersityIndex,ZetaPotentialMv,pH,EndotoxinsEU,SterilityTest,HeavyMetalsPPM

Example (sterility: 0=sterile, 1=contaminated; parent impurity: leave blank if N/A):
RN-2026-001,Ga-68,LNP,Lungs,45000.0,94.5,7.0,0.0005,100.0,0.15,-25.0,6.8,120.0,0,5.0

Supported configurations:
• Radionuclides: Ga-68, Zr-89, Cu-64, F-18, I-124
• Nanoparticle types: Liposomes, LNPs, Polymer NPs
• Target organs: Lungs, Liver, Tumor, Spleen

— WHY IS THIS NEEDED?
Radiolabeled nanoparticles represent an emerging class of theranostic agents combining:
• Targeted drug delivery (nanocarrier advantages)
• Real-time biodistribution tracking (radionuclide imaging)
• Potential for image-guided therapy

However, quality control is complex due to dual nature:
• Radiochemical parameters (like traditional radiopharmaceuticals)
• Nanoparticle parameters (size, stability, surface charge)
• Interaction between radionuclide and carrier (affects biodistribution)

⚠️ CRITICAL PARAMETERS:
• Specific activity: Must be sufficient for imaging sensitivity while maintaining nanoparticle integrity
• Radiochemical purity: ≥90% (Ga-68) or ≥95% (Zr-89, Cu-64, F-18, I-124)
• Free radionuclide: ≤10% (Ga-68, I-124) or ≤5% (Zr-89, Cu-64, F-18) — affects biodistribution
• Parent nuclide impurity: ≤0.001% for generator-produced nuclides (Ge-68 for Ga-68)
• Particle size: Organ-specific optimal ranges (e.g., 50-150 nm for lung targeting via capillary entrapment)
• Polydispersity index: ≤0.3 for monodisperse distribution (consistent biodistribution)
• Zeta potential: -30 to +30 mV for colloidal stability

Key features:
• Adaptive parameter limits based on radionuclide and target organ
• Support for 5 radionuclides with different half-lives and applications
• Organ-specific nanoparticle size optimization (lungs vs liver vs tumor)
• Comprehensive safety checks (endotoxins, sterility, heavy metals)
• Research-focused design with clear investigational status disclaimers

Critical parameters by radionuclide:
• Ga-68: Specific activity ≥30 GBq/μmol, purity ≥90%, Ge-68 ≤0.001%, free Ga-68 ≤10%
• Zr-89: Specific activity ≥15 GBq/μmol, purity ≥95%, free Zr-89 ≤5% (78.4h half-life)
• Cu-64: Specific activity ≥20 GBq/μmol, purity ≥95%, free Cu-64 ≤5% (theranostic applications)
• F-18: Specific activity ≥50 GBq/μmol, purity ≥95%, free F-18 ≤5% (short half-life critical)
• I-124: Specific activity ≥10 GBq/μmol, purity ≥90%, free I-124 ≤10% (4.2d half-life)

Nanoparticle size optimization by target:
• Lungs (LNP): 50-150 nm — optimal for capillary entrapment (Nature Biomed Eng 2023)
• Liver (Liposomes): 80-200 nm — Kupffer cell uptake
• Tumor (Liposomes): 100-200 nm — enhanced permeability and retention (EPR) effect
• Spleen (Polymer): 200-500 nm — splenic filtration

💡 Usage tips:
1. Verify radionuclide-specific parameters match your conjugation chemistry
2. Particle size must be measured by DLS (dynamic light scattering) immediately before use
3. Zeta potential indicates colloidal stability — values outside -30 to +30 mV risk aggregation
4. Free radionuclide measurement requires separation method (size exclusion chromatography, dialysis)
5. Document all parameters for ethics committee reporting and study reproducibility

⚠️ Limitations:
• Parameters based on preclinical research — may require adjustment for specific formulations
• Not a substitute for in vivo biodistribution studies
• Utility does NOT replace official pharmacopoeial methods
• Intended for research use only — not for clinical administration
• Final specifications must be validated per local regulatory requirements

Data sources:
• Nature Biomedical Engineering 2023 — Lung-targeted lipid nanoparticles (LuT lipids)
• ACS Nano 2021 — Nanoparticle biodistribution and targeting principles
• Journal of Nuclear Medicine 2022 — Radiolabeled nanoparticle quality control
• European Pharmacopoeia — Radiopharmaceutical specifications
• International Journal of Pharmaceutics 2020 — Liposomal drug delivery systems

input.csv

BatchNumber,Radionuclide,NanoparticleType,TargetOrgan,SpecificActivityMBqPerUmol,RadiochemicalPurityPercent,FreeRadionuclidePercent,ParentNuclideImpurityPercent,ParticleSizeNm,PolydispersityIndex,ZetaPotentialMv,pH,EndotoxinsEU,SterilityTest,HeavyMetalsPPM
RN-2026-001,Ga-68,LNP,Lungs,45000.0,94.5,7.0,0.0005,100.0,0.15,-25.0,6.8,120.0,0,5.0
RN-2026-002,Zr-89,Liposome,Liver,18000.0,96.0,4.0,,150.0,0.20,-28.0,7.0,100.0,0,3.0
RN-2026-003,Cu-64,Polymer,Tumor,25000.0,95.5,4.5,,120.0,0.18,-22.0,6.5,150.0,0,4.0

URS & FS — user requirements and functional specification

This document defines user requirements and functional specification for the quality-control utility. It supports deployment discussion, IQ/OQ preparation and QC workflow integration.

Utility: RadiolabeledNanoparticleQualityCheckerAPI / object: Radiolabeled NanoparticleCategory: Radiopharmaceuticals

1. Scope

The Radiolabeled Nanoparticle Quality Checker utility is used for Radiolabeled Nanoparticle. The actual input.csv is the source of truth for the input structure; control criteria are defined by the executable and the domain description.

The utility does not use machine learning; decisions are produced by deterministic rules.

Categories: Radiopharmaceuticals

Tags: decay correction, endotoxins, heavy metals, impurities, PET, radionuclide purity, radiopharma, SPECT, sterility

2. Execution modes

RadiolabeledNanoparticleQualityChecker.exe                            → demo mode (console output)
RadiolabeledNanoparticleQualityChecker.exe input.csv output.json      → evaluate your data

3. Key controlled areas

purity and impurities
microbiology and pathogens
heavy metals / elemental impurities
pH and physicochemical parameters
activity, decay and radiochemical purity

4. Domain limits and critical parameters

⚠️ IMPORTANT: INVESTIGATIONAL USE ONLY
⚠️ CRITICAL PARAMETERS:
Specific activity: Must be sufficient for imaging sensitivity while maintaining nanoparticle integrity
Radiochemical purity: ≥90% (Ga-68) or ≥95% (Zr-89, Cu-64, F-18, I-124)
Free radionuclide: ≤10% (Ga-68, I-124) or ≤5% (Zr-89, Cu-64, F-18) — affects biodistribution
Parent nuclide impurity: ≤0.001% for generator-produced nuclides (Ge-68 for Ga-68)
Particle size: Organ-specific optimal ranges (e.g., 50-150 nm for lung targeting via capillary entrapment)
Polydispersity index: ≤0.3 for monodisperse distribution (consistent biodistribution)
Zeta potential: -30 to +30 mV for colloidal stability
Adaptive parameter limits based on radionuclide and target organ
Support for 5 radionuclides with different half-lives and applications
Organ-specific nanoparticle size optimization (lungs vs liver vs tumor)
Comprehensive safety checks (endotoxins, sterility, heavy metals)
Research-focused design with clear investigational status disclaimers
Critical parameters by radionuclide:
Ga-68: Specific activity ≥30 GBq/μmol, purity ≥90%, Ge-68 ≤0.001%, free Ga-68 ≤10%
Zr-89: Specific activity ≥15 GBq/μmol, purity ≥95%, free Zr-89 ≤5% (78.4h half-life)
Cu-64: Specific activity ≥20 GBq/μmol, purity ≥95%, free Cu-64 ≤5% (theranostic applications)
F-18: Specific activity ≥50 GBq/μmol, purity ≥95%, free F-18 ≤5% (short half-life critical)
I-124: Specific activity ≥10 GBq/μmol, purity ≥90%, free I-124 ≤10% (4.2d half-life)
Lungs (LNP): 50-150 nm — optimal for capillary entrapment (Nature Biomed Eng 2023)
Liver (Liposomes): 80-200 nm — Kupffer cell uptake
Tumor (Liposomes): 100-200 nm — enhanced permeability and retention (EPR) effect
Spleen (Polymer): 200-500 nm — splenic filtration

Limits stated in the description must be verified against the current approved specification, pharmacopoeial monograph and registration dossier before production use.

5. URS — user requirements

ID	Requirement	Criticality	Acceptance criterion
URS-001	The system shall accept an `input.csv` file for Radiolabeled Nanoparticle with the exact columns listed in the “Input data contract” section.	High	A file with the correct header is processed without manual editing; missing mandatory columns produce FAIL/import error.
URS-002	The system shall support execution without arguments in demo mode and execution with `input.csv output.json` for user data.	Medium	Both execution scenarios produce a predictable result or clear diagnostic error.
URS-003	The system shall perform rule-based controls for: purity and impurities, microbiology and pathogens, heavy metals / elemental impurities, pH and physicochemical parameters, activity, decay and radiochemical purity.	High	Each controlled parameter receives a status and message; the result does not depend on hidden Excel formulas or ML.
URS-004	The system shall preserve traceability between batch/lot, source values, applied rules and final verdict.	High	Output includes batch identifier, source values, parameter statuses and critical findings.
URS-005	The system shall generate machine-readable `output.json` for LIMS/ELN/MES, batch record and QA/QC review.	High	JSON contains overall status, check array, warnings, failures and source-file reference.
URS-006	The system shall support use in the client validation package: URS/FS, IQ/OQ preparation, installation and operational scenario checks.	High	The document, test scenarios and reproducible CSV/JSON flow are suitable for audit and internal approval.
URS-007	The system shall clearly separate technical data errors from specification nonconformities.	Medium	Schema/type errors are not mixed with pharmacopoeial deviations and are reported separately.

6. input.csv data contract

The source of truth for the input schema is the actual input.csv header. Column names are technical identifiers and are not translated.

#	Column	Type	Unit	Description	Sample	Control rule
1	`BatchNumber`	identifier	as specified	Batch Number	`RN-2026-001`	mandatory field; used for batch/lot traceability
2	`Radionuclide`	text	as specified	Radionuclide	`Ga-68`	mandatory value; format and acceptability are checked by the utility
3	`NanoparticleType`	text	as specified	Nanoparticle Type	`LNP`	mandatory value; format and acceptability are checked by the utility
4	`TargetOrgan`	text	as specified	Target Organ	`Lungs`	mandatory value; format and acceptability are checked by the utility
5	`SpecificActivityMBqPerUmol`	decimal	MBq	Specific Activity MBq per Umol	`45000.0`	mandatory numeric value; rule comparison is performed by the utility
6	`RadiochemicalPurityPercent`	decimal	%	Radiochemical Purity %	`94.5`	numeric value; compared with assay/purity limit from specification or method
7	`FreeRadionuclidePercent`	decimal	%	Free Radionuclide %	`7.0`	mandatory numeric value; rule comparison is performed by the utility
8	`ParentNuclideImpurityPercent`	decimal	%	Parent Nuclide Impurity %	`0.0005`	numeric value; compared with individual or total impurity limit
9	`ParticleSizeNm`	decimal	µm	Particle Size Nm	`100.0`	mandatory numeric value; rule comparison is performed by the utility
10	`PolydispersityIndex`	decimal	as specified	Polydispersity Index	`0.15`	mandatory numeric value; rule comparison is performed by the utility
11	`ZetaPotentialMv`	decimal	as specified	Zeta Potential Mv	`-25.0`	mandatory numeric value; rule comparison is performed by the utility
12	`pH`	decimal	pH	p H	`6.8`	mandatory numeric value; rule comparison is performed by the utility
13	`EndotoxinsEU`	decimal	as specified	Endotoxins EU	`120.0`	numeric value; critical safety attribute compared with endotoxin limit
14	`SterilityTest`	boolean / flag	0/1	Sterility Test	`0`	valid flag required; prohibited organisms and growth are normally expected as 0 / absent
15	`HeavyMetalsPPM`	decimal	ppm	Heavy Metals PPM	`5.0`	numeric value; checked as elemental/metal impurity

CSV example

BatchNumber,Radionuclide,NanoparticleType,TargetOrgan,SpecificActivityMBqPerUmol,RadiochemicalPurityPercent,FreeRadionuclidePercent,ParentNuclideImpurityPercent,ParticleSizeNm,PolydispersityIndex,ZetaPotentialMv,pH,EndotoxinsEU,SterilityTest,HeavyMetalsPPM
RN-2026-001,Ga-68,LNP,Lungs,45000.0,94.5,7.0,0.0005,100.0,0.15,-25.0,6.8,120.0,0,5.0

7. FS — functional specification

ID	Function	Implementation description
FS-001	CLI entry point	The executable `RadiolabeledNanoparticleQualityChecker.exe` supports demo mode and `input.csv output.json` processing mode.
FS-002	CSV parser	The import module reads CSV, validates header, column presence/order, value count and encoding. Decimal values are expected with a dot separator.
FS-003	Field conversion	Each column is converted to the expected type: identifier, text, decimal number, date/time or boolean flag.
FS-004	Domain rule engine	For Radiolabeled Nanoparticle, explicit rules are applied: range, minimum, maximum, absence of prohibited flag, data completeness or calculation-based check.
FS-005	Criticality handling	Critical violations produce FAIL; non-critical deviations and incomplete data produce WARNING; full conformance produces PASS.
FS-006	JSON writer	`output.json` stores overall status, per-parameter results, source values, warnings, failures and diagnostic messages.
FS-007	Integration contract	The CSV → JSON format is stable for invocation from LIMS/ELN/MES, scheduled task or wrapper service.
FS-008	Error handling	Schema error, missing file, non-numeric value or JSON write failure returns diagnosable error without silent PASS.

8. output.json contract

The output file must be suitable for automated processing, audit review and correlation with the source input.csv row.

{
  "utility": "RadiolabeledNanoparticleQualityChecker",
  "api": "Radiolabeled Nanoparticle",
  "batchNumber": "RN-2026-001",
  "overallStatus": "PASS|WARNING|FAIL",
  "checkedAtUtc": "2026-05-18T00:00:00Z",
  "checks": [
    {
      "parameter": "BatchNumber",
      "value": "RN-2026-001",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Radionuclide",
      "value": "Ga-68",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "NanoparticleType",
      "value": "LNP",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "TargetOrgan",
      "value": "Lungs",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "SpecificActivityMBqPerUmol",
      "value": "45000.0",
      "unit": "MBq",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "RadiochemicalPurityPercent",
      "value": "94.5",
      "unit": "%",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "FreeRadionuclidePercent",
      "value": "7.0",
      "unit": "%",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "ParentNuclideImpurityPercent",
      "value": "0.0005",
      "unit": "%",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    }
  ],
  "criticalFindings": [],
  "sourceFile": "input.csv"
}

9. OQ/PQ test scenarios

ID	Scenario	Expected result
TC-001	Valid CSV with expected header and sample row	All rows are processed; output contains PASS/WARNING/FAIL and parameter-level detail.
TC-002	A mandatory input.csv column is missing	Import is rejected or the row receives FAIL with schema reference.
TC-003	A numeric field contains text or a blank value	Type conversion error is recorded; the result is not hidden as PASS.
TC-004	A parameter is outside specification or critical limit	Critical parameters produce FAIL; non-critical deviations produce WARNING according to the rule.
TC-005	Positive pathogen/microbiological flag or microbiological limit excursion	Critical FAIL is produced with the offending parameter.
TC-008	Incorrect activity, reference time or radiochemical purity	FAIL/WARNING is produced with calculation traceability.

10. QA/QC, CSV and change control

Before production use, the client records executable version, checksum, specification/monograph version, test CSV, expected JSON and IQ/OQ results.
Column names must not be changed without updating the validator and test scenarios.
The source CSV, output.json and utility version should be stored together as an evidence package.
Any change in control rules must go through change control and repeated OQ scenario verification.

Included in packages

Cardiology QC Suite

QC package for cardiology medicines: antihypertensives, anticoagulants, antiplatelets, lipid-lowering and antiarrhythmic medicines plus supporting QC checks.

Open

PetRad QC Suite

A specialised utility package for radiopharmaceutical quality control: PET, SPECT, therapeutic radionuclides, generators and decay calculations.

Open

Radiology QC Suite

QC package for radiology and diagnostic imaging: radiopharmaceuticals, PET/SPECT, contrast media, iodinated and gadolinium products, plus particle, sterility and endotoxin checks.

Open

RPH organ/system: hepatobiliary and GI

HIDA, mebrofenin, gallbladder, gastric emptying, GI transit, bleeding and liver/spleen imaging.

Open

RPH organ/system: oncology and theranostics

Tumour imaging, PSMA/FAPI/receptor tracers, immuno-PET, targeted radionuclide therapy and radioembolization.

Open

RPH organ/system: pulmonary and ventilation

Lung perfusion, MAA, V/Q, aerosol, xenon ventilation, shunt and pulmonary dosimetry.

Open

RPH use case: generators, isotope purity and starting radionuclides

Control of generator eluate, breakthrough, radionuclidic purity, isotope mix, carrier/free radionuclides and starting radionuclides before labeling.

Open

RPH workflow: generators and isotope purity

Generator eluate, breakthrough, radionuclidic purity, isotope mix and starting radionuclides.

Open

RPH workflow: imaging QC and quantitative interpretation

Acquisition, uptake, clearance, perfusion, transit, ejection fraction, segmentation and quantitative imaging.

Open

RPH workflow: product release QC

Assay, purity, sterility, endotoxins, pH, impurities, appearance and batch-release checks.

Open

RPH workflow: stability, storage, decay and waste

Kinetic stability, shelf life, decay correction, expiry, storage, trend and radioactive waste.

Open

RPH: combined radiopharmaceutical QC package

RPH combines PetRad, PetRad2 and PetRad3 into one umbrella package for PET/SPECT, therapeutic radionuclides, generators, labelled compounds, decay calculations, sterility, endotoxins and radiochemical/radionuclidic purity.

Open