Malignant tumors are one of the major causes of death today, and the efficacy of single treatment is often unsatisfactory. For more than 100 years, the development of external radiotherapy has brought benefits to tumor patients, but also brought some serious side effects and complications that are difficult to avoid. In order to minimize the side effects of radiotherapy and the damage to normal tissues, inter-tissue brachytherapy with radioactive particles has emerged. 1.Basic concept Inter-tissue brachytherapy is a method to treat tumor by implanting a closed radiation source into the tumor tissue or the tissues infiltrated by cancer cells nearby (including the tissues with lymphatic spread). The term “brachytherapy” refers to the placement of radioisotopes within 5 cm of the tumor tissue or even within the tumor tissue for treatment. Radioactive particle implantation includes transient insertion and permanent implantation. The former commonly used radioisotopes are 192Ir and 137Cs, and the radioactive source is transported to the tumor tissue site for irradiation treatment through a post-loading treatment machine. The latter commonly used isotopes include 198Au, 103Pd and 125I, which can be inserted between tissues through template implantation, ultrasound or CT-guided implantation, intraoperative or endoscopic implantation, etc. In 1914, Dr. Pastean and Dr. Degrais first used radium particle implantation to treat prostate cancer, which pioneered the treatment of prostate cancer with particle implantation. In 1993, Mittal et al. developed a computerized treatment planning system and ultrasound-guided template implantation technology, which enabled more uniform distribution of radioactive particles in the target area and less damage to surrounding tissues. In the mid-1990s, the rapid development of imaging and radiation physics, as well as the emergence of computerized treatment planning systems, postoperative analysis systems and new radionuclides, further developed and improved this technology. In 1998, Shanghai Central Hospital, Shanghai Chest Hospital, Shanghai Eighth Hospital and other 10 hospitals reported more than 1000 cases of particle implantation for malignant tumor treatment, with more than 20,000 125I particles implanted, and none of the group showed leukopenia or radiation sickness. At present, more than 2000 hospitals in China have carried out this work, and achieved good results. 3.Treatment principle and advantages Inter-tissue implantation of radioactive particles brachytherapy is to implant a low-dose miniature radioactive source into the tumor tissue or the tissue invaded by the tumor, through the miniature radioactive source emitting continuous low-energy γ-rays to kill the tumor cells and make the tumor cells lose the ability to reproduce. γ-rays have a direct effect on the DNA molecular chain: single chain break, double bond break; at the same time, they have an indirect effect: to make the body The ionization of water molecules in the body, resulting in free radicals. Free radicals interact with biological macromolecules and cause tissue cell damage. In the DNA synthesis phase and mitosis phase, the tumor tissue is most sensitive to γ-rays, and a small amount of γ-rays can destroy the reproductive ability of tumor cells and kill them. Therefore, the low dose of γ-rays generated by radioactive particles can continuously act on tumor tissues and continuously kill tumor cells entering DNA synthesis and mitosis to achieve therapeutic purposes. The tumor cells with different division cycles in the tumor tissue are evenly irradiated, while the surrounding normal tissues are insensitive to radiotherapy because they are in the quiescent phase of cell division, and only slightly damaged. At the same time, the dose to the normal tissues outside the tumor can be sharply reduced because of the small radioactivity of the particles, thus reducing the damage to the surrounding normal tissues. Compared with external radiotherapy, inter-tissue implantation of radioactive particles in brachytherapy has obvious biological advantages: (1) the duration of local treatment of tumor is long. ②The dose of radiation therapy is lower. ③Low damage to surrounding normal tissues. ④Strong killing power to tumor cells. 4.The conditions, indications and contraindications of radioactive particle implantation therapy Radioactive particle implantation therapy belongs to the category of brachytherapy, but it is different from traditional brachytherapy. Particle implantation therapy generally requires three basic conditions: ① radioactive particles. ②Particle implantation 3D treatment planning system and quality verification system. (3) The auxiliary equipment required for particle implantation. 4.1 Indications ①Untreated primary cancer, such as prostate cancer. ②Tumor localized or regional spread lesions, especially those involving important tissues or difficult to be removed surgically. ③In order to reduce the scope of surgery and preserve important functional tissues, a combination of limited lesion excision and brachytherapy is feasible. ④Recurrent or metastatic cancer with isolated lesions; ⑤After external radiotherapy, there are still local residual cancer foci due to dose or tissue tolerance. 4.2 Contraindications Active bleeding, necrosis or ulceration at the tumor site, extensive lesions, inappropriate for radiotherapy (such as hematological diseases) and contraindications to anesthesia, etc. 5.The method of radioactive particle implantation The operation of radioactive particle implantation is as follows: firstly, through the information of tumor and surrounding organs provided by ultrasound, CT and MRI, the two-dimensional diameter of the tumor is measured, and the data is input into the three-dimensional treatment planning system, and finally the total radiation dose of particles, the number of particles, the exact site of particle implantation and the spacing of particles are obtained, so that the particles have uniform dose distribution in the three-dimensional direction, The radiation dose to the surrounding normal tissue is minimized. The tumor is then surgically exposed, and under ultrasound or CT guidance, the puncture needles are inserted into the tumor as planned, with each needle arranged in parallel, and the particles are then implanted into the tumor at different depths with a particle implantation gun. The marginal particles should be located 0.5-1.0 cm below the tumor surface, and the adjacent organs should be moved away as much as possible before implantation to minimize the dose to these organs and tissues. Postoperative radiographs are taken to determine the site of implantation, to show the relationship between the treated portion and the surrounding normal tissue, and to obtain a radiation dose distribution map to verify that the dose distribution after implantation is consistent with the treatment plan. CT plays an important role in the radioactive particle implantation technique because of its good spatial resolution and density resolution, which can accurately display the size and shape of the lesion, the necrotic cavity area within the lesion, and the anatomical relationship with the adjacent tissue structures. The anatomical relationship with the adjacent tissue structures. The data collected are input into the computerized stereotactic system to design the treatment plan, select the best skin injection point and injection path to avoid damaging important structures such as blood vessels and nerves, and calculate the effective dose and distribution of tumor killing, particle number and distribution location. After that, particle implantation is performed under the guidance of CT, and the particles are implanted into the tumor according to the dose distribution map of the solid tumor simulated by computer. 6. clinical application of radioactive particle implantation 6.1 brain tumors The brain tumors currently treated by radioactive particle implantation include: brain astrocytoma, brain glioma, brain metastases, etc. Halligan et al. treated 22 cases of highly differentiated recurrent brain astrocytoma with 125I particles, and the median survival of the whole group was 65 weeks, with an actual annual survival rate of 57%. Sneed et al. reported a median survival time of 51 weeks for recurrent gliomas and 53 weeks for grade III gliomas after radiation particle therapy, with 3-year survival rates of 14% and 23%, respectively. Most scholars believe that surgical treatment should be preferred for large brain tumors, and when surgery cannot completely remove the tumor, low-dose radioactive particle implantation therapy can be given. 6.2 Nasopharyngeal carcinoma is a radiation-sensitive tumor, and radiotherapy can often achieve good results. However, due to its hidden anatomical location and narrow and irregular structure in the nasopharyngeal cavity, the application of clinical surgical treatment and intracavitary radiotherapy is very limited. Inter-tissue implantation of radioactive particles under the localization and guidance of CT and sinus endoscopy can improve the local tumor-free control rate. Cai Dejiang et al. treated 76 cases of local residual or recurrent nasopharyngeal carcinoma with 198Au, and the results showed that the local control rates were 87.5% and 49.3% in the residual and recurrent groups, respectively, and the 6-year actual survival rates were 76% and 35.2%, respectively. 6.3 Lung cancer Surgical resection is preferred for early stage lung cancer cases, however, the risk of surgery increases if the tumor invades blood vessels or local lymph nodes entangle blood vessels; moreover, lung cancer is generally more malignant, and most patients have lost the opportunity of surgery when it is detected. For patients with stage I non-small cell lung cancer with poor general condition and unsatisfactory cardiopulmonary function, surgical resection is somewhat limited, and radioactive particle implantation therapy under direct vision with television thoracoscopy or small incision can be used. The average postoperative hospital stay was 7 d and the follow-up was 11 months. The chest CT scans showed no migration of 125I particles or local recurrence of tumor in all patients. Therefore, the study concluded that thoracoscopy with intraoperative 125I particle implantation is a promising treatment for patients with stage I non-small cell lung cancer with suboptimal cardiopulmonary function. 6.4 Hepatocellular carcinoma Primary hepatocellular carcinoma is a highly malignant tumor, and surgery is the main treatment method for it, and the recurrence rates of hepatocellular carcinoma 1 and 2 years after surgery reach 56.9% and 81%, respectively. Radioactive particle implantation for hepatocellular carcinoma is one of the current combined treatment methods. It is indicated for untreated primary carcinoma, local or regional infiltrative areas, especially those involving important tissues, which are difficult to be removed surgically, and recurrent or metastatic carcinoma. Radioactive particle implantation under laparoscopy has both diagnostic and therapeutic effects. Yang Shaofang et al. applied radioactive particle implantation to treat four cases of liver cancer, and the results showed that the treatment was accurate and the surrounding tissues and organs were less damaged. 6.5 Prostate cancer The treatment of early stage prostate cancer includes surgery and external radiotherapy. However, these treatments can cause more serious late damage, such as impotence and nerve damage. In recent years, with the development of CT localization technology and transrectal ultrasound imaging technology, the treatment of prostate cancer with radioactive particle implantation has made great progress. The results of a multicenter study showed that if the quality of radioactive particle implantation can be guaranteed (≥140Gy), the local control rate of 125I radioactive particle implantation therapy is comparable to that of external radiotherapy, and both methods have shown good efficacy under the same grade and stage of prostate cancer. The effect is comparable to radical surgery, and it is less invasive, faster recovery, and can be performed on an outpatient basis, so it has gradually replaced surgery. With the successful development of new radionuclides such as 100Pd and the application of B-ultrasound and CT three-dimensional treatment planning system, the inter-tissue implantation of radioactive particles for brachytherapy is more precise in positioning and more uniform and reasonable in dose distribution. For those tumors that recur after surgery, especially after surgery and radiotherapy, particle implantation therapy is undoubtedly a more reasonable and effective treatment route. However, there are still many clinical problems to be solved: (1) how to select different radionuclides for tumors with different proliferation rates in order to obtain the maximum killing effect. (2) How to combine particle implant brachytherapy with surgery, external radiotherapy, hormone therapy and chemotherapy, etc. (3) The prospect of clinical application of new radionuclides such as 241Am and 152Cf needs to be further clarified. In conclusion, inter-tissue implantation of radioactive particles for the treatment of tumors has a broad prospect for clinical application due to the advantages of low trauma to normal tissues, uniform dose distribution in the target area and easy protection for medical personnel.