Application of 32P Radioactive Patch in Keloid Treatment

Summary

This protocol describes in detail the specific process and its efficacy for patients suffering from keloids who are treated with the ³²P Radioactive Patch. It covers medical equipment, lesion sampling, dressing device production, application methods, and post-operative care.

Abstract

Keloid, as a benign fibroblastic disease of the skin, is the result of excessive proliferation of fibroblasts and abnormal deposition of collagen during the process of skin trauma repair. Clinically, this disorder presents as a fibrous proliferation that protrudes beyond the surface of the skin beyond the margins of the original injury, affecting both function and aesthetics. In clinical treatment, the ³²P radioactive patch is a well-established and effective treatment based on the biological effect of β-rays, which can penetrate keloid tissue, induce apoptosis of fibroblasts in the keloid, impede cell proliferation, and inhibit excessive collagen synthesis and deposition, and eventually achieve the desired therapeutic effect after a period of treatment. However, because radiation naturally decays over time and because keloids have variability in dose requirements and size from patient to patient, ³²P radioactive patches usually need to be custom dispensed according to the patient's specific situation. This article will provide a detailed overview of the manufacturing process for ³²P radioactive patch radiation applicators, methods of calculating radiopharmaceutical doses, as well as specific procedures and considerations for clinical application.

Introduction

Keloids are benign skin lesions that can significantly impact appearance and are often associated with pain, burning sensations, itching, and, in some cases, impaired limb function, leading to considerable detriment to quality of life^1,2. During the skin wound healing process, keloids grow excessively due to the interplay of various factors, including molecular, cellular, physiological, biochemical, and physical elements. This interaction disrupts the body's repair mechanisms, resulting in the abnormal overgrowth of keloid tissues³. Keloids gradually protrude from the skin's surface, extending beyond the original area of damage and infiltrating adjacent healthy tissues without natural resolution⁴. Treatment methods are generally categorized into surgical intervention, laser, physical, and drug treatments⁵. Although these methods exhibit inhibitory effects on keloids, they have various limitations. Some of these approaches exhibit minimal efficacy, while others are costly or yield unsatisfactory clinical outcomes^6,7. Therefore, it is particularly important to find a treatment that is both effective and economical. In contrast, using radioactive isotopes (such as ³²P, ⁹⁰Y,¹⁸⁸ Re, ⁶⁶ Ho, ⁹⁰Sr), which release beta radiation, can significantly inhibit keloid overgrowth and is considered one of the most effective treatment methods⁸. Pure β rays target keloids by modulating fibroblast activity, inhibiting collagen fiber synthesis, blocking micro vessels, and reducing blood supply⁹.

Among the various isotopes available (such as ³²P, ⁹⁰Y, ¹⁸⁸Re, ⁶⁶Ho, and ⁹⁰Sr), ³²P is the most cost-effective option for clinical use. The commonly employed ³²P radioactive patches are primarily custom-made, with a physical half-life of 14.3 days. Of note, ³²P emits β particles with a maximum energy of 1.71 MeV. The maximum tissue absorption range is approximately 7.5 mm, most of which is absorbed at depths of 3 to 4 mm¹⁰. Importantly, the ³²P radioactive patch only irradiates the surface lesion, minimizing damage to surrounding or deeper tissues and organs. The current clinical indications for this approach include keloids and skin hemangiomas.

The aim of this study is to introduce a homemade ³²P radiation patch and to discuss in detail its clinical application in keloid treatment and its potential significance. Compared with traditional treatment methods, such as laser therapy, ⁹⁰Sr radiotherapy, etc., the ³²P radiation patch has higher targeting and lower side effects, which can effectively improve the treatment effect⁸. In addition, radioisotope therapy has been shown to have significant advantages in reducing the recurrence rate of keloids¹¹. Therefore, understanding the indications, treatment process, and potential effects of the ³²P radiation patch will help patients and clinicians who are considering this approach to make more informed treatment decisions. Radioactive patch treatment targets collagen fibroblasts produced in keloid tissues, subsequently inducing cell apoptosis, mitochondrial damage, endothelial cell swelling in capillaries, gradual blood vessel blockage, causing local blood circulation disorders, and inhibiting the growth, proliferation, and differentiation of fibroblasts. This reduces collagen synthesis and deposition, thereby achieving the desired therapeutic outcome⁷.

Protocol

The study protocol was reviewed and approved by the Clinical Research Approval Committee of the First Affiliated Hospital, Zhejiang University School of Medicine [2025B] IIT Ethics Approval No.0225. Written informed consent was obtained from all subjects.

CAUTION: Radioactive compounds that emit ionizing radiation may present health risks to humans. Therefore, all procedures involving radioactive reagents are conducted with appropriate protective measures to minimize radiation exposure to operators and the surrounding environment. The use of radioactive compounds is strictly regulated at both institutional and national levels. The procedures described in this article were conducted at the Nuclear Medicine Department of Zhejiang University First Hospital, where radiological personnel receive training on handling open-source radiation and adhere to established operational practice guidelines. All operators are required to undergo specialized training in radioactive operations.

1. Patient selection

1. Inclusion criteria
   1. Select patients who show clinical manifestations, including the presence of keloids, are aged between 18 and 70 years, and following a skin injury, the keloid protrudes from the skin surface and exhibits a tendency for continued proliferation. The wound surface may present sensations of tightening, itching, or burning, while the texture of the wound is often hard, congested, flushed, uneven, and irregularly shaped.
2. Exclusion criteria
   1. Exclude patients unwilling or unable to adhere to this treatment, patients with unhealed wounds accompanied by infection or ulcers, and those with severe coagulation dysfunction, and patients with other significant systemic diseases, such as those affecting the hematopoietic, cardiovascular, or hepatic conditions, to name a few.

2. Lesion delineation

1. After explaining the procedure, alternatives, benefits, and risks in detail to the patient, and after ensuring that the patient understands all the matters, ask the patient to sign an informed consent form.
2. Marking and photographing: Mark the lesion's precise location and orientation.
3. Sampling: Mark the outline of the skin lesion with a black marker and then, using tape containing adhesive on one side, stick it to the skin that has been outlined by the marker, peel off the tape to topstitch the shape outlined by the marker, then stick the tape to white paper and cut out the topstitched shape along the outline. Using the shape as a template, outline the shape on filter paper and cut it out. A filter paper in the shape of this lesion is available. (Figure 1A,B).
4. Next, mark the specific location and orientation of the lesion with a pencil on the cut-out sample paper, clearly indicating where the top and bottom margins are (Figure 1C,D).
5. Use a treatment chart to document the patient's basic information, lesion size, pixel density per cm² of the standard sample paper, and the area of each lesion. Use the calculation method shown below.

3. Area calculation of lesions

1. Position a 1 cm² reference paper and the sample filter paper on a black background, ensuring the unmarked side faces up. Capture the image using a high-fidelity camera (Figure 2A).
2. Open the image on a computer equipped with Image J software. Click on File > Open or drag the image directly into the menu bar (Figure 2B). Then, convert the image to the 8-bit format (Figure 2C).
3. Click on Adjust > Threshold (Figure 2D), dragging the slider to the value of 200, until the overlapping red color aligns with the sample paper area, and click Apply (Figure 2E). When finished, the filter paper will appear white (Figure 2F).
4. To count, click the option for Analyze > Analyze for Particles (Figure 2G). The software will calculate the pixels for each graphic (Figure 2H). Use the 1.0 cm² reference pixels to calculate the area of each lesion.
5. Based on this method, calculate and record the area of each lesion. For each cm² of lesion, calculate the dosing volume at 20.0 µL/cm².

4. Registering for the ³²P preparation

1. Use the medication sodium phosphate [³²P] pertechnetate for the plaster preparation. This medicine is supplied by manufacturers qualified in the production of radiopharmaceuticals, and it's commercially available as a finished medicine.
   NOTE: Structural formula: Na-³²PO₄(H)-Na; Molecular formula: Na₂H³²PO₄; Molecular weight: 142. This medication appears as a colorless, clear liquid and has a shelf life of 30 days from the manufacture date.
2. Record the configuration date.
3. Add the following calculated volume of normal saline (NS), which includes the medication marked volume plus NS volume, which is greater than the required volume for treatment. For instance, if the delivery volume is 1.4 mL and 2.0 mL is required for treatment, adding 1.0 mL of normal saline would suffice.
4. Preparation concentration (mCi/mL): Enter the correct treatment data in the Preparation Date field (typically, the treatment date is the same day as the preparation date). Perform calculations based on the activity values in Table 1. Calculate the data required for sample preparation for each patient based on the activity values on the day. All data are summarized in Table 2.
5. Duration of treatment: Calculate the time with reference to the dose required for the patient's treatment. Referring to the expert consensus and individualized according to the thickness and location of the keloid and the patient's response, choose the nuclear medicine that is the appropriate dose after comprehensive judgment. For example, 20 Gy requires 200 min, 30 Gy requires 300 min, and 40 Gy requires 400 min.

5. Plaster medication application

1. Ask the technician A to measure background radiation levels in the work area and confirm the drug dosage form with the attending clinician.
2. Ask the technician A to double-check with the attending clinician and add saline to the ³²P stock solution (Figure 3).
3. Ask technician B to prepare a transparent film dressing, choosing the type according to the size of the lesion. For this treatment, remove the filter paper from the patient, ensuring that the front, back, and correct orientation are clearly visible.
4. Ask both technician A and technician B to check together the different parts of the patient and the dose for each part. There may be single or multiple sites of scarring on the same patient, each of which is different in size and shape, and may require different doses of medication for different sites. Number the multiple sites to ensure accurate manipulation and check information such as the number and dose of each site.
5. Ask technician A to refer to Table 1, add the specified dose of saline solution to the ³²P stock solution to dilute it, then refer to Table 2 and use a pipette to add the accurate dose of solution to each piece of filter paper. After adding the solution, dry the filter paper.
6. Ask technician B to assist in attaching the filter paper to the center of the two transparent film dressings, using the schematic diagram of ³²P radioactive patch layering (Figure 4A). Place it in the foil box and hand it to the nurse (Figure 4B).
7. Place the remaining medication in the lead bucket provided for decay treatment. At the end of production, check and record the radiation level of the work area.
8. ³²P radioactive patch quality control
   1. Check the surface of the applicator for contamination. Wipe the front and back of the applicator with a dry cotton swab dipped in saline, then use a radiation dose detector to check that the radiation counts on the swab are at background levels.
   2. Uniformity of ³²P solution distribution on the filter paper: Homogeneously mix the ³²P solution with methylene blue, an aromatic heterocyclic compound that produces a dark blue solution and is commonly used as a staining agent in medical applications. Spot the mixture onto filter paper using a micropipette and observe the color uniformity on the filter paper to indirectly assess the distribution uniformity of the ³²P solution (Figure 5).

6. Fixed dressing application

1. Upon receipt of the dressing box, ³²P radioactive patch, and treatment planner, verify the patient's name and treatment site with the supervising clinician.
2. Use a disposable razor to remove hair from the area as needed and wipe with a cotton ball moistened with 75% alcohol to remove contamination and skin oils.
3. Remove the back of the transparent film dressing, identify the part, size, and direction, then align with the target area and apply to the patient's affected area. If in doubt, communicate with the supervising clinician to confirm correct dressing application (Figure 6).
4. Confirm the start time of dressing treatment with the supervising clinician. Based on the duration of treatment required for this area as shown in Table 2, record the start and end times. and inform the patient of the end time to allow for the timely removal of the ³²P radioactive patch. Advise the patient of the precautions to be taken during treatment as described below.
   1. Refrain from doing any vigorous exercise activities or bathing during dressing treatment to avoid soaking the dressing.
   2. When using a dressing applicator in areas with skin folds, protect the adjacent skin to prevent radiation injury.
   3. There are no specific dietary contraindications. However, avoid spicy, irritating, and allergenic foods.
5. At the end of the treatment time, remove the dressing. Wear latex gloves on both hands and gently remove the dressing, starting from the side of the dressing to ensure complete removal of the entire dressing. Record the time and inform the patient of the end of treatment for home skin care as described below. Place the retrieved ³²P radioactive patch in the lead bucket provided and complete the record.
   1. If the area appears red, swollen, or black, perform no special treatment. Avoid scratching, rubbing, or irritating the area with soap, and avoid using too hot water to rinse directly.
   2. For peeling skin, perform no special treatment, avoid strong hand buckling, tearing, and other actions.
   3. For pain or itching, do not scratch or rub, do not rinse with particularly hot water, avoid irritating soap cleaning, and try to choose a mild shower gel. If the pain or itching is unbearable, seek medical attention.
   4. For blisters, for small blisters, do not perform any special treatment; small blisters rupture on their own, and need to be sterilized with iodine povidone daily. For medium and large blisters, seek medical attention.
   5. For ulceration, seek medical attention and use medications as prescribed by the clinician.
   6. There are no special dietary restrictions. Try to avoid spicy, irritating, and allergenic foods.
   7. Bathing: If the skin is not ulcerated, bathing can be done. Avoid scratching, rubbing, irritating the scar with soap, and using too hot water directly on the scar to rinse.
6. Efficacy evaluation criteria: Check for improvement or disappearance of clinical symptoms (itching, pain, and so on), keloid softening, flattening of thickness, volume reduction, and lightening of local skin color to near-normal skin tone. Conduct a comprehensive assessment by inquiring about the patient's symptoms, observing the keloid in general, and measuring both the keloid area and thickness

7. Guidelines for the safe handling and disposal of radioactive medical waste

1. Perform radiological procedures in designated areas (e.g., dispensing cabinets). Wear appropriate personal protective equipment (PPE), such as lead aprons, collars, goggles, gloves, masks, and safety glasses.
2. Always use radiation dose monitoring equipment and wear a personal dosimeter to monitor radiation exposure. Monitor changes in environmental background levels before and after operations.
3. Dispose of all potentially contaminated items as radioactive waste.
4. In general, the following safety guidelines and measures should be observed when handling radiopharmaceuticals. According to the National Ecological Environmental Standard of the People's Republic of China (HJ 1188-2021) on Radiation Protection and Safety Requirements for Nuclear Medicine, collect ³²P radioactive waste separately and store for decay treatment. For radioactive waste containing nuclides with a half-life of more than 24 h, store for more than 10 times the longest half-life of the nuclide. Once the activity concentration of the radionuclide has been reduced to a level that meets the criteria for deregulation, dispose of it as normal clinical waste.

Results

Material selection
For the preparation of phosphorus-32 (³²P) patches, various types of filter paper were sourced from reputable local suppliers. The insoluble matrix designed to retain radioactive substances must exhibit permeability, ductility, and liquid adsorption capabilities. The choice of filter paper type for impregnation with the appropriate medicinal solution significantly impacts the reliability of experimental outcomes. Owing to its balanced permeability and sufficient flexibil...

Discussion

The use of ³²P radioactive patches for keloid treatment is among the most established and widely used methods in the clinical applications of nuclear medicine¹⁴. This approach involves applying the radioactive isotope patch close to the surface lesion, leveraging the biological effects of ionizing radiation to induce morphological and functional changes in the cells of the local lesion tissue to achieve the therapeutic purpose¹⁵.

The p...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
75% alcohol cotton balls	Cixi City Huabao Medical Supplies Industry & Trade Development Company	MQ/LJ-small	Cleansing and disinfecting the skin.
Filter Paper	Hangzhou Special Paper Industry Company	3#	The agent for adsorbing 32P solution.
Image J	National Institutes of Health(NIH)	Image processing software	https://imagej.net/ij/
Manual Pipettes	Eppendorf AG	3123000292   3123000233  3123000250	Accurate measurement and movement of medicinal liquids.
Medical disposable sterilization rubber gloves	Sri Trang Gloves(Thailand)Public Company Limited	F840	Protects hands from contamination.
Saline	China Otsuka Pharmaceutical Company	2C97B4	Dilute solution and configure drug.
Sodium Phospate[32P] Oral Solution	Atomic High Tech Company	H10960254	Provide 32P radioactive source.
Surface Contamination Monitor	IMI International Inc.	Inspector Alert V2	Surface contamination monitoring.
Transparent Film Dressing Frame Style	3M Company	1624W 9546HP	Closed filter paper, protecting the skin.